Neuropsychological Testing Under the Medical Benefit – Commercial and Individual Exchange Medical Policy

Neuropsychological Testing Under the Medical Benefit

Page 1 of 33

UnitedHealthcare Commercial and Individual Exchange Medical Policy

Effective 09/01/2024

UnitedHealthcare

Commercial

and Individual Exchange

Medical

Policy

Neuropsychological Testing Under the Medical Benefit

Policy Number: 2024T0152BB

Effective Date: September 1, 2024

 Instructions for Use

Table of Contents Page

Application ............................................................................. 1

Coverage Rationale .............................................................. 1

Definitions .............................................................................. 2

Applicable Codes .................................................................. 3

Description of Services ......................................................... 3

Clinical Evidence ................................................................... 4

U.S. Food and Drug Administration .................................... 26

References .......................................................................... 26

Policy History/Revision Information .................................... 32

Instructions for Use ............................................................. 32

Application

UnitedHealthcare Commercial

This Medical Policy applies to all UnitedHealthcare Commercial benefit plans.

UnitedHealthcare Individual Exchange

This Medical Policy applies to Individual Exchange benefit plans in all states except for Colorado.

Coverage Rationale

Neuropsychological testing is proven and medically necessary for evaluating individuals with the following

conditions when the results of testing will be used to support a diagnosis, prognosis, or treatment plan:

• Attention-deficit/hyperactivity disorder (ADHD) when all of the following are present:

o Specific neurocognitive behavioral deficits related to ADHD need to be evaluated; and

o Testing has been recommended by a physician and is related or secondary to a known or suspected organic-

medical condition resulting from brain injury or disease process (e.g., concussion, intractable seizure disorder,

cancer treatment effects, genetic disorders, inborn errors of metabolism)

Note: The scope of these criteria is applicable only to neuropsychological testing that is covered by the medical

benefit. These criteria do not apply to evaluate or determine educational interventions.

• Confirmed space-occupying brain lesion including but not limited to the following:

o Brain abscess

o Brain tumors

o Arteriovenous malformations within the brain

• Demyelinating disorders including multiple sclerosis

• Intellectual disability or intellectual developmental disorder when all of the following are present:

o The intellectual disability or intellectual developmental disorder is associated with a known or suspected medical

cause (e.g., Traumatic Brain Injury, in utero toxin exposure, early seizure disorder, sickle cell disease, genetic

disorders); and

o The intellectual disability or intellectual developmental disorder meets all of the following criteria (DSM-5):

 Deficits in intellectual function, such as reasoning, problem solving, planning, abstract thinking, judgment,

academic learning, and learning from experience, confirmed by both clinical assessment and individualized,

standardized intelligence testing; and

Related Commercial/Individual Exchange Policy

•

Maximum Dosage and Frequency

Community Plan Policy

• Neuropsychological Testing Under the Medical

Benefit

Related Optum Clinical Guideline

• Psychological and Neuropsychological Testing

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 Deficits in adaptive functioning that result in failure to meet developmental and sociocultural standards for

personal independence and social responsibility (without ongoing support, the adaptive deficits limit

functioning in one or more activities of daily life, such as communication, social participation, and independent

living across multiple environments, such as home, school, work, and community); and

 Onset of intellectual and adaptive deficits during the developmental period

Note: The scope of these criteria is applicable only to neuropsychological testing that is covered by the medical

benefit. These criteria do not apply to evaluate or determine educational interventions.

• Encephalopathy including acquired immunodeficiency syndrome (AIDS) encephalopathy, human immunodeficiency

virus (HIV) encephalopathy, hepatic encephalopathy, Lyme disease encephalopathy including neuroborreliosis,

Wernicke's encephalopathy, and systemic lupus erythematosus (SLE) encephalopathy

• Neurocognitive disorders including mild cognitive impairment (MCI), dementia or symptoms of dementia such as

memory impairment or memory loss (including Alzheimer’s and extrapyramidal disorders such as Parkinson's

disease) that is associated with a new onset or progressive memory loss and a decline in at least one of the following

cognitive domains (DSM-5):

o Complex attention

o Executive function

o Learning and memory

o Language

o Perceptual motor

o Social cognition

• Neurotoxin exposure with at least one of the following:

o Demonstrated serum levels of neurotoxins

o Individual with one or more of the following:

 Documented prenatal alcohol, drug, or toxin exposure

 History of radiation therapy or chemotherapy

• Seizure disorder including individuals with epilepsy

• Stroke

• Traumatic Brain Injury (TBI)

• The individual is being considered for a medical or surgical procedure that may affect brain function (e.g., epilepsy

surgery, resection of brain tumors or arteriovenous malformations, deep brain stimulation, stem cell or organ

transplants)

The following are unproven and not medically necessary due to insufficient evidence of efficacy:

• Baseline neuropsychological testing in asymptomatic individuals at risk for sport-related concussions

• Computerized cognitive testing such as Cognivue

, Mindstreams

Cognitive Health Assessment, BrainCare

™

, and

QbTest

• Computerized neuropsychological testing when used as a stand-alone test for evaluating concussions

• Neuropsychological testing for the following diagnoses alone without other proven conditions as noted above:

o Headaches including migraine headache

o History of myocardial infarction

o Intermittent explosive disorder

• Neuropsychological testing that is comprised exclusively of self-administered or self-scored inventories, or as

screening tests of cognitive function or neurological disease whether paper-and-pencil or computerized (e.g., AIMS,

Folstein Mini-Mental Status Examination)

• Neuropsychological testing that is used as a routine screening tool

• Neuropsychological testing that is administered for educational or vocational purposes that do not alter or direct

medical or health management

• Repeat neuropsychological testing that is not required for medical decision-making

• The individual is neurologically, cognitively, or psychologically unable to participate in a meaningful way in the

neuropsychological testing process

• The individual has been diagnosed previously with brain dysfunction, such as Alzheimer’s disease, and there is no

expectation that neuropsychological testing would impact the individual’s medical, functional, or behavioral

management

Definitions

Traumatic Brain Injury (TBI): TBI is defined as a bump, blow, or jolt to the head or a penetrating head injury that disrupts

the normal function of the brain. (Centers for Disease Control and Prevention, 2021)

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Applicable Codes

The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all

inclusive. Listing of a code in this policy does not imply that the service described by the code is a covered or non-covered

health service. Benefit coverage for health services is determined by the member specific benefit plan document and

applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to

reimbursement or guarantee claim payment. Other Policies and Guidelines may apply.

CPT Code

Description

96116

Neurobehavioral status exam (clinical assessment of thinking, reasoning and judgment, [e.g.,

acquired knowledge, attention, language, memory, planning and problem solving, and visual spatial

abilities]), by physician or other qualified health care professional, both face-to-face time with the

patient and time interpreting test results and preparing the report; first hour

96121

Neurobehavioral status exam (clinical assessment of thinking, reasoning and judgment, [e.g.,

acquired knowledge, attention, language, memory, planning and problem solving, and visual spatial

abilities]), by physician or other qualified health care professional, both face-to-face time with the

patient and time interpreting test results and preparing the report; each additional hour (List

separately in addition to code for primary procedure)

96132

Neuropsychological testing evaluation services by physician or other qualified health care

professional, including integration of patient data, interpretation of standardized test results and

clinical data, clinical decision making, treatment planning and report, and interactive feedback to the

patient, family member(s) or caregiver(s), when performed; first hour

96133

Neuropsychological testing evaluation services by physician or other qualified health care

professional, including integration of patient data, interpretation of standardized test results and

clinical data, clinical decision making, treatment planning and report, and interactive feedback to the

patient, family member(s) or caregiver(s), when performed; each additional hour (List separately in

addition to code for primary procedure)

96136

Psychological or neuropsychological test administration and scoring by physician or other qualified

health care professional, two or more tests, any method; first 30 minutes

96137

Psychological or neuropsychological test administration and scoring by physician or other qualified

health care professional, two or more tests, any method; each additional 30 minutes (List separately

in addition to code for primary procedure)

96138

Psychological or neuropsychological test administration and scoring by technician, two or more

tests, any method; first 30 minutes

96139

Psychological or neuropsychological test administration and scoring by technician, two or more

tests, any method; each additional 30 minutes (List separately in addition to code for primary

procedure)

96146

Psychological or neuropsychological test administration, with single automated, standardized

instrument via electronic platform, with automated result only

CPT

is a registered trademark of the American Medical Association

Description of Services

Neuropsychological testing is a set of formal procedures utilizing diagnostic tests specifically focused on identifying the

presence of brain damage, injury, or dysfunction and any associated functional deficits. Measurement of deficits cannot

be based on single test results and should always be assessed in the context of the medical and neurological

examination. Neuropsychological testing is customarily associated with neurological diagnoses rather than behavioral

health diagnoses.

Neuropsychological tests are administered in a variety of contexts including paper-and-pencil, computers, and visual aids.

Following an initial clinical interview with a neuropsychologist, tests are strategically selected to identify specific deficits

and preserved abilities. Standardized tests are then administered by a trained technician or neuropsychologist. Some

tests offer multiple forms making them useful for repeated administration to the same patient, thereby minimizing practice

effects. In light of the numerous procedures available for assessment of different neurocognitive functions, test selection is

based on familiarity of the examiner with certain tests, availability of appropriate normative data, ability of the patient to

participate in testing, and validity of particular procedures for the specific function being measured.

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Neuropsychological tests include but are not limited to the following: Boston Diagnostic Aphasia Examination (BDAE),

Conners' Continuous Performance Test (CCPT), Controlled Oral Word Association Test (COWAT), Delis-Kaplan Test

Battery, Freedom from Distractibility Index (FFDI) from the Wechsler Intelligence Scales, Gordon Diagnostic System

(GDS), Halstead-Reitan Neuropsychological Battery, Repeatable Battery for Assessment of Neuropsychological Status

(RBANS), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterreith Complex Figure Test, Stroop Color and Word

Test, Test of Variables of Attention (TOVA), Trail Making Tests, Wechsler Adult Intelligence Scale-Revised (WAIS-III/IV),

Wide Range Assessment of Memory and Learning (WRAML), and Wisconsin Card Sorting Test (WCST). At times,

neurocognitive measures are supplemented by emotional functioning and personality testing and include but are not

limited to the following: Minnesota Multiphasic Personality Inventory-2 (MMPI-2)/Minnesota Multiphasic Personality

Inventory-A (MMPI-A), Personality Assessment Inventory (PAI), Geriatric Rating Scale, Beck Depression Inventory (BDI),

Beck Anxiety Inventory (BAI), and Rorschach Inkblot Method.

Computerized testing for dementia and cognitive impairment including the Mindstreams

Cognitive Health Assessment

(NeuroTrax

Corp.) uses computer-based assessments in an attempt to identify cognitive impairment in the elderly. The

software programs give individuals various stimuli or puzzles to solve using a mouse or a keypad. The Mindstreams

system automatically generates a report that details the individual’s performance in the standard cognitive domains, or

areas, e.g., memory, attention, executive function, visual spatial perception, verbal skills, motor planning, and information

processing. According to NeuroTrax, BrainCare

™

is the current version of the original MindStreams product. Cognivue

(Cerebral Assessment Systems, Inc.) is another computerized cognitive test that is intended for early detection of

dementia signs. Individuals take the 10-minute test using the Cognivue mobile computer workstation to assess visuomotor

coordination, perceptual processing, and memory. Cognivue is intended to help identify patients who may be in the early

stages of dementia and should undergo further evaluation. The QbTest is an online computerized test that measures

activity, attention, and impulsivity for assessment of attention-deficit hyperactivity disorder (ADHD).

Computerized neuropsychological tests have been proposed to be used as part of the overall medical management of

concussion to monitor recovery. Most computer-based cognitive assessment tools are designed to detect the speed and

accuracy of attention, memory, and thinking ability. Currently available computerized tests include ImPACT (Immediate

Post-Concussion Assessment and Cognitive Testing, ImPACT Applications, Inc.), ANAM (Automated Neuropsychological

Assessment Metrics, the United States Army Medical Department), CogState Sport (Axon Sports, Ltd.), and HeadMinder

(Headminder, Inc.). These tests are being investigated for baseline testing of asymptomatic persons and managing

concussions once they occur.

Neuropsychological testing is within the scope of the provider’s professional training and licensure when the provider is

any of the following:

• A doctoral-level psychologist who is licensed to practice independently and demonstrates sufficient training and

experience

• A credentialed psychiatrist who meets the following requirements:

o Recognized certification in neurology through the American Board of Psychiatry and Neurology;

o Accreditation in behavioral neurology and neuropsychiatry through the American Neuropsychiatric Association;

o State medical licensure specifically allowing for the provision of neuropsychological testing service(s);

o Evidence of professional training and expertise in the specific tests and/or assessment measures for which

authorization is requested;

o Physician and supervised psychometrician(s) adhere to the prevailing national professional and ethical standards

regarding test administration, scoring, and interpretation

• A board-certified neurologist

Refer to the following Optum Supplemental Clinical Criteria for more information:

• Psychological/Neuropsychological Testing Guidelines (to access this guideline, go to:

Optum Provider Express >

Clinical Resources > Guidelines/Policies/Manuals > Supplemental Clinical Criteria). Accessed May 15, 2024.

Clinical Evidence

Attention Deficit Hyperactivity Disorder (ADHD)

Peterson et al. (2024) conducted a systematic review for The Agency for Healthcare Research and Quality (AHRQ) to

assess the evidence on the diagnosis, treatment, and monitoring of ADHD in children and adolescents to inform a

planned update of the American Academy of Pediatrics guidelines. The review included 550 studies reported in 1, 097

publications (231 studies addressed diagnosis, 312 studies addressed treatment, and 10 studies addressed monitoring).

The studies that addressed diagnosis included studies that evaluated the diagnostic performance of parental ratings,

teacher rating scales, teen/child self-reports, clinician tools, neuropsychological tests, EEG approaches, imaging, and

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biomarkers. Studies that evaluated neuropsychological tests of executive functioning used study-specific combinations of

individual cognitive measures which made it more difficult to compare performance across studies. The authors stated

that evaluation of specific tools was difficult as many of the studies assessed a large number of different tools within

broader categories, used different components of the same tools, or combined components in a variety of ways. Of the

231 studies that addressed diagnosis, there were 74 that included neuropsychological tests, assessing executive function,

and/or encompassing a variety of cognitive assessments, including continuous performance tests, to diagnose ADHD with

high variability in study designs, inclusion/exclusion criteria, and reported sensitivity, specificity, and accuracy in their

outcomes. The authors reported that about a third of the studies included race and ethnicity demographics with seven

studies having populations with more than 50% of the participants being White, and with the proportion of girls in the study

populations ranging from none to 74%. The authors reported that multiple approaches showed promising diagnostic

performance; however, the strength of evidence (SoE) was generally low with few studies reporting estimates for children

under the age of seven. The authors concluded that there are many diagnostic tools available to aid in the diagnosis of

ADHD and that further research is needed to assess performance of diagnostic tools for ADHD in children under the age

of seven years.

Bausela-Herreras et al. (2024) conduced a systematic review and meta-analysis to determine the usefulness of the

Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and to analyze the possible ceiling and

floor effect of its scores in the assessment of executive function (EF) in preschoolers (age range between two and six

years) with signs compatible with a possible diagnosis of ADHD. The study included seven articles with 2311 participants

under 6 years of age with ADHD-compatible symptoms (n = 1459) compared to typically developing (TD) participants (n =

791). One study also included children with oppositional defiant disorder (ODD; n = 51) and ODD + ADHD (n = 10). The

floor effect was described as when most participants score very low on an evaluation, indicating that the measure used

may not be sensitive enough to capture variations in performance and the ceiling effect occurs when most participants

score very high, suggesting that the measure may not be able to distinguish adequately between higher levels of ability or

performance. The authors reported that executive deficits in early-age individuals with symptoms compatible with ADHD

are more extensive than just deficits in working memory and that a floor effect was found in tests associated with the

Flexibility clinical scale and the Emotional Control index, both hot executive functions, and a ceiling effect was associated

with two of the BRIEF-P indices: Global Executive Functioning and the Emergent Metacognition index, configured by the

clinical scales Working Memory and Planning/Organization, which are indices associated with the cold dimensions of

executive functions. The authors concluded that the BRIEF-P is an instrument that facilitated obtaining a sensitive and

discriminative executive profile, although it should be used in combination with other neuropsychological performance

tests. Limitations of the study included including the small sample sizes of six of the seven studies, the average age of the

participants (before ADHD diagnosis) precluded considering the influence of factors related to developmental stage and

maturity and the inclusion of participants with ODD.

Becke et al. (2023) administered a comprehensive neuropsychological test battery in an analogue study that included 57

adults with ADHD, and 211 university students who were divided into two groups with 60 students in the control group,

and 151 students in the simulator group to evaluate individual test’s utility in detecting noncredible performance.

Participants in the simulator group were then divided to receive one of three sets of instructions: naive simulators received

general instructions to feign ADHD and no additional information, symptom-coached simulators were given the DSM

diagnostic criteria of ADHD, and fully coached simulators received information on both the neuropsychological

assessment of ADHD and its diagnostic criteria. Analysis by the authors of the test results demonstrated that the

Simulation Group showed a higher median number of test results falling into the suspect range based on the newly

derived cut-off scores than the ADHD Group and Control Group. The authors reported that all of the tests ensured at least

90% specificity in the ADHD Group, but that sensitivity differed significantly between tests, ranging from 0% to 64.9%. The

authors concluded that tests focusing on selective attention, vigilance, and inhibition were most useful in detecting the

instructed simulation of adult ADHD, while tests focusing on figural fluency and task switching lacked sensitivity.

Limitations of the study include the single center and simulation study design, the lack of heterogeneity in the pool used to

select the control and simulation groups and the risks associated with the embedded validity indicators in some of the

tests and from the risk of overfitting.

Pagán et al. (2023) performed a systematic review to assess the diagnostic utility of the Conner’s Continuous

Performance Test (CCPT) for diagnosing ADHD in adults. Their review and analysis included 35 published studies with

sample sizes ranging between 24 and 413 participants that assessed symptoms for both childhood and adults. The

authors stated that there was moderate reliability, subpar discriminant and ecological validity, and mixed sensitivity and

specificity for the CCPT. They concluded that their review gave support to previous critiques of the CCPT’s diagnostic and

utility as a treatment measure and stated that clinicians should assess information from multiple sources when diagnosing

ADHD in an adult patient. Limitations of the study include the exclusion of adults with comorbidities from most of the

included studies, the heterogeneity in study designs of the studies reviewed including how ADHD was assessed between

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studies, the instruments being used, the diagnostic measures and outcomes, and the lack of control groups in many of the

included studies.

Bechtel et al. (2012) evaluated whether boys with epilepsy-related ADHD and developmental ADHD share a common

behavioral, pharmaco-responsive, and neurofunctional pathophysiology. Seventeen boys with diagnosed combined

epilepsy/ADHD, 15 boys with developmental ADHD, and 15 healthy controls (aged 8-14 years) performed on working

memory tasks (N-back) while brain activation was recorded using functional magnetic resonance imaging. On a

behavioral level, boys with epilepsy-related ADHD as well as those with developmental ADHD performed similarly poorly

on tasks with high cognitive load when compared to healthy controls. On the functional level, both patient groups showed

similar reductions of activation in all relevant parts of the functional network of working memory when compared to

controls. The study data showed strong similarities between epilepsy-related and developmental ADHD on the behavioral,

pharmaco-responsive, and neural level, favoring the view that ADHD with and without epilepsy shares a common

underlying neurobehavioral pathophysiology.

Dementia, Possible Dementia, Memory Loss/Impairment and Mild Cognitive

Impairment (MCI)

For memory impairment or dementia screening, a single test of global measures of function or a measure of cognitive

function is usually administered along with a test of behavioral or emotional symptoms. In addition to brief screening tests,

for some patients, comprehensive neuropsychological testing may be indicated to confirm a diagnosis, evaluate effects of

treatment, and assist in designing rehabilitative or intervention strategies for the patient. Standardized test batteries are

too long for most patients with dementia; specialized dementia batteries or an individualized test battery is usually more

appropriate.

A definitive diagnosis of Alzheimer's disease (AD) is based on the presence of memory deficits along with deficits in at

least one other aspect of cognition, and in some cases is made on neuropsychological test results alone (Talwalker,

1996). Impairment in primary (short-term) memory alone is not a useful diagnostic marker for AD in the early stages.

Tests of delayed recall (long-term memory) and retrieval of facts of common knowledge have been shown to be the most

useful measures to distinguish normal aging and early AD. Dementia due to AD can be distinguished from dementia due

to vascular disease by differences in pattern of memory impairment and the progressive nature of AD (Costa et al., 2017).

Careful interpretation of test results, taken in conjunction with medical findings, allows differentiation of AD from normal

memory loss due to aging, and from vascular dementia.

Quaranta et al. (2023) conducted a single-center, longitudinal study with 253 patients (129 (51%) women; mean age

72.95 years) with Mild Cognitive Impairment (MCI) to assess the possible role of neuropsychological profiles at the

baseline in predicting the rate of progression from MCI to overt dementia. Participants underwent evaluation every six

months for six years with a neuropsychological battery that included the Mini-Mental State Examination (MMSE), Rey

Auditory Verbal Learning Test (RAVLT), copy and delayed recall of the Rey–Osterrieth Complex Figure (ROCF),

phonological verbal fluency, categorial verbal fluency, copy of figures with and without landmarks, Raven’s Colored

Progressive Matrices, Stroop’s test, digit span forward and backward, objects naming, and the Multiple Features Targets

Cancellation. Each participant also underwent brain MRI and PET-FDG examination to confirm neurodegenerative

pathology and to exclude other pathologies. Participants were assessed by a neurologist blinded to the results of the

baseline neuropsychological examination and the diagnosis of dementia was formulated if the clinical criteria for dementia

due to AD were met. The diagnosis of AD was confirmed in a following visit after six months. The authors reported that

186 converted to dementia and 67 remained stable at the sixth year of follow-up. There were 27 patients who progressed

in the first two years (fast converters), 107 converted in the third and fourth year (intermediate converters) and 51 who

converted after the fourth year of follow-up (slow converters). The authors reported that participants with stable MCI

performed better than fast decliners in MMSE), several long-term memory scores, and category verbal fluency test (CFT)

while stable and intermediate converters differed only in the MMSE and CFT tests, and stable and slow converters

differed only in MMSE and phonological/semantic discrepancy score. The authors concluded that early impairment of

semantic memory could predict the evolution to AD before the onset of episodic memory disorders, and that the

discrepancy between phonological and semantic verbal fluency could be able to detect impairment in advance in respect

of simple CFT tests. Limitations of the study include the single-center design and the small sample size.

In a test validation study on the cross-cultural dementia (CCD) screening test for diagnosing AD and Parkinson's disease,

Delgado-Álvarez et al. (2023) recruited 150 participants from a single outpatient center and divided them into three groups

with 30 participants with AD with mild dementia (AD-D), 30 participants with AD in mild cognitive impairment (AD-MCI), 30

participants with mild cognitive impairment associated with Parkinson’s disease (PD-MCI) and 60 participants in the

healthy control (HC) group (50% for comparisons with AD, 50% for comparisons with PD-MCI) with no significant

differences in age, education, and sex. A comprehensive neuropsychological test battery and the CCD screening test

were completed for each participant. The authors reported that intergroup differences were found according to the

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cognitive profile of each clinical condition and that the CCD test described differences in executive functions and speed

scores comparing AD-MCI and PD-MCI. They also noted correlations between standardized neuropsychological tests and

CCD measures which they stated support the convergent validity of the CCD test. The authors concluded that the CCD

test showed good discrimination properties and cut-off scores for dementia and that the CCD test would be useful as a

novel cognitive tool in the assessment of patients with cognitive impairment in different neurological conditions. Limitations

of the study included the single-center design, the lack of a group of participants with Parkinson’s disease that were

cognitively preserved, the generally low level of education of the participants, and the lack of evaluation of cognitive

reserve.

The Agency for Healthcare Research and Quality (AHRQ) wanted to identify which individual cognitive tests or

combinations of cognitive tests are most accurate for clinically diagnosing clinical Alzheimer’s-type dementia (CATD).

AHRQ noted that there were no evidence-based guidelines about the merits of either brief cognitive testing or

comprehensive neuropsychological testing in this patient population and that access to comprehensive

neuropsychological testing is limited in many clinical settings. Fink et al (2020) completed a Comparative Effectiveness

Review for AHRQ in which they analyzed 56 studies on the accuracy of brief cognitive tests for CATD and found that

multiple brief cognitive tests were highly sensitive and specific for distinguishing CATD from normal cognition, but less so

for distinguishing mild CATD from normal cognition or CATD from mild cognitive impairment (MCI).

In a systematic review and meta-analysis, Belleville et al. (2017) determined the extent to which cognitive measures can

predict progression from mild cognitive impairment (MCI) to Alzheimer's type dementia (AD), assessed the predictive

accuracy of different cognitive domain categories, and determined whether accuracy varies as a function of age and

length of follow-up. The authors systematically reviewed and meta-analyzed data from longitudinal studies reporting

sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will develop AD. Twenty-

eight studies met the eligibility criteria (2365 participants) and reported predictive values from 61 neuropsychological tests

with a 31-month mean follow-up. Values were pooled to provide combined accuracy for 14 cognitive domains. Many

domains showed very good predictive accuracy with high sensitivity and specificity values. Verbal memory measures and

many language tests yielded very high predictive accuracy. Other domains (e.g., executive functions, visual memory)

showed better specificity than sensitivity. Predictive accuracy was highest when combining memory measures with a

small set of other domains or when relying on broad cognitive batteries. The authors concluded that neuropsychological

assessment can strongly contribute to predicting dementia while individuals are still in the MCI phase. According to the

authors, cognitive tests are excellent at predicting MCI individuals who will progress to dementia and should be a critical

component of any toolkit intended to identify AD at the pre-dementia stage.

Pedersen et al. (2017) examined the incidence, progression, and reversion of mild cognitive impairment in patients with

Parkinson disease (PD-MCI) over 5 years. A population-based cohort of patients with incident PD underwent repeated

neuropsychological testing of attention, executive function, memory, and visuospatial abilities at baseline (n = 178), 1 year

(n = 175), 3 years (n = 163), and 5 years (n = 150). Patients were classified as PD-MCI and diagnosed with dementia

according to published criteria. Thirty-six patients (20.2%) fulfilled criteria for PD-MCI at baseline. Among those with

normal cognition at baseline (n = 142), the cumulative incidence of PD-MCI was 9.9% after 1 year, 23.2% after 3 years,

and 28.9% after 5 years of follow-up. Overall, 39.1% of patients with baseline or incident PD-MCI progressed to dementia

during the 5-year study period. The conversion rate to dementia was 59.1% in patients with persistent PD-MCI at 1-year

vs 7.2% in those with normal cognition during the first year. A total of 27.8% of patients with baseline PD-MCI and 24.2%

of those with incident PD-MCI had reverted to normal cognition at study end, but the reversion rate decreased to 9.4% in

those with persistent PD-MCI at 2 consecutive visits. Compared with cognitively normal patients, PD-MCI reverters within

the first 3 years of follow-up were at increased risk of subsequently developing dementia. The authors concluded that

early PD-MCI, regardless of persistence or reversion to normal cognition, has prognostic value for predicting dementia in

patients with PD.

Developmental Disorders

In general, empirical data, rather than evidence from prospective studies with long-term follow-up, support the use of

neuropsychological testing for developmental disorders in infants and children.

In a multi-centered, longitudinal study that evaluated the sensitivity of the NIH Toolbox Cognition Battery (NIHTB-CB) to

detect developmental changes in persons with intellectual disability (ID), Shields et al. (2023) administered the NIHTB-CB

and the Stanford-Binet Intelligence Scales, Fifth Edition (SB5), a reference standard cross-validation measure to 256

individuals (ages six to 25 years old at visit 1 with a minimum mental age equivalent of three years) with fragile X

syndrome (FXS), Down syndrome (DS), and other ID (OID). After two years (median time between visits was 25.92

months), the authors retested 197 of the participants at visit 2 and assessed group developmental changes in each

cognitive domain of the NIHTB-CB and SB5 at three age points (10, 15 and 22 years). The authors reported that the effect

sizes of growth measured by the NIHTB-CB tests were comparable with or exceeded those of SB5 and that the NIHTB-

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CB showed significant gains in almost all domains in OID at younger ages (10 years) with continue gains at 15 years and

stability in early adulthood (22 years) and that some significant improvements were seen in mid-adolescence and early

adulthood, such as attention/inhibitory control in all groups, episodic memory in DS, working memory, receptive

vocabulary, and oral reading in OID and DS, and processing speed in FXS and DS. Limitations of the study included the

use of only two assessment periods, the difficulty in recruiting participants in the lower and upper ranges, and the inherent

challenges in assessing the youngest participants with significant ID. The authors concluded that the NIHTB-CB was

sensitive to developmental changes in individuals with ID etiologies and recommended future research to evaluate the

battery more to establish sensitivity to change within the context of treatment studies and delineation of clinically

meaningful changes in NIHTB-CB scores.

Tricket et al. (2022) conducted a parallel mediation analysis with cross-sectional data from 152 extremely premature (EP;

< 27 weeks of gestation) children and 120 term-born controls who were assessed at age 11 to identify specific cognitive

mechanisms that are associated with poor academic attainment in children born preterm for the development of

interventional strategies. Mathematics and reading attainment were evaluated to assess the following mediators: verbal

working memory, visuospatial working memory, verbal processing speed, attention, and visuospatial processing. The

authors reported that children born EP had significantly lower mean composite mathematics and reading scores than

controls equating to a deficit of −1.1 SD in reading and −1.4 SD in mathematics, after adjusting for sex and socio-

economic status. When children with severe neurodevelopmental disability were excluded, the difference in means,

adjusted for sex and socio-economic status, remained significant for reading (−0.4 SD) and mathematics (−1.0 SD).

Lower scores were also reported by the authors for verbal working memory (-0.5 SD), visuospatial working memory (-0.7

SD), attention (-0.6 SD), visuospatial processing (-1.1 SD) and verbal processing speed (-0.6 SD) although the magnitude

of difference in all five neuropsychological skills were decreased but still significant when children with severe disability

were excluded. The authors concluded that children born before 27 weeks of gestation had substantially poorer

attainment in reading and mathematics compared to children born at term and that their study identified that a

combination of neuropsychological skills including verbal working memory, visuospatial working memory and visuospatial

processing may be especially important to target in interventions to improve mathematics and reading outcomes for EP

children with average to moderately low IQ. Limitations of the study include the inability of some EP children with severe

neurodevelopmental disabilities to complete the entire battery of tests, the recruitment of controls from mainstream

schools as this may not be reflective of the general population, the limited time available to assess each child within

school, and the use of cross-sectional data for mediation models.

Johnson et al. (2016) explored comorbidity in intellectual disability (ID) and learning disabilities (LD) in children born

extremely preterm (EP; < 26 + 0 weeks gestation). A UK national cohort of 161 EP children and 153 term-born controls

without neurosensory impairments was assessed at 11years of age (the EPICure Study). Neuropsychological abilities

commonly affected by EP birth were assessed using the NEPSY Developmental Neuropsychological Test. Overall, 75

(47%) EP children and 7 (4.6%) controls had ID or LD. Comorbidity in ID/LD was more common among EP children than

controls (24% vs. 0%). EP children with comorbid ID/LD had significantly poorer neuropsychological abilities and

curriculum-based attainment than EP children with an isolated disability or no disabilities. LD was associated with a 3

times increased risk for special educational needs (SEN). However, EP children with ID alone had poorer

neuropsychological abilities and curriculum-based attainment than children with no disabilities, yet there was no increase

in SEN provision among this group. The authors concluded that EP children are at high risk for comorbid intellectual and

learning disabilities. According to the authors, education professionals should be aware of the complex nature of EP

children’s’ difficulties and the need for multi-domain assessments to guide intervention.

Hartman et al. (2010) examined the motor skills and executive functions in school-age children with borderline and mild

intellectual disabilities (ID). Sixty-one children aged between 7 and 12 years diagnosed with borderline ID (33 boys and 28

girls; 71 < IQ < 79) and 36 age peers with mild ID (24 boys and 12 girls; 54 < IQ < 70) were assessed. Their abilities were

compared with those of 97 age- and gender-matched typically developing children. Qualitative motor skills, i.e., locomotor

ability and object control, were evaluated with the Test of Gross Motor Development (TGMD-2). Executive functioning

(EF), in terms of planning ability, strategic decision-making and problem solving, was gauged with the Tower of London

(TOL) task. Compared with the reference group, the full ID cohort scored significantly lower on all assessments.

According to the investigators, the study results support the notion that besides being impaired in qualitative motor skills,

intellectually challenged children are also impaired in higher-order executive functions. The authors conclude that deficits

in the two domains are interrelated, so early interventions boosting their motor and cognitive development are

recommended.

Traumatic Brain Injury

Longitudinal and case-controlled studies along with numerous case reports support the use of neuropsychological tests to

assess the severity of injury and the prognosis for patients with closed head trauma, to monitor progression, and to

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provide measures of outcome for determining degree of recovery (Ekdahl et al. 2023; Filipčíková et al., 2022; Hanks et al.,

2016; Carlozzi et al., 2015).

Other Disorders

Neuropsychological testing may have a role in the clinical management of the following medical disorders:

• Brain lesions including abscesses, tumors, and arteriovenous malformations in the brain (Pertichetti et al., 2023;

Söderström et al., 2022; Pranckeviciene et al., 2017; Meskal et al., 2016; Walsh et al., 2016; Cochereau et al., 2016)

• Demyelinating disease including multiple sclerosis (Ezegbe et al., 2023; Delgado-Álvarez et al., 2022; Fuchs et al.,

2022; Tekin et al., 2022; Böttrich et al., 2020; Wojcik et al., 2019; von Bismarck et al., 2018; Ruet and Brochet, 2018;

Vollmer et al., 2016)

• Encephalopathy (Sigurdardottir et al., 2022; Rayes et al., 2019; Moore et al., 2017; Burton et al., 2017)

• Epilepsy and seizure disorders (Fox et al. 2024; Allebone et al. 2023; Silberg et al., 2020; Parra-Díaz and García-

Casares, 2017; Grau-López et al., 2017; Wilson et al., 2015; Filippini et al., 2016; Patrikelis et al., 2016)

• Neurotoxin exposure (Nascimento et al., 2016)

• Stroke (Kusec et al. 2023; Zuo et al., 2022; Lo Buono et al., 2018; Tan et al., 2017; Zweifel-Zehnder et al., 2015;

Chen et al., 2015)

Computerized Neuropsychological Testing for Concussion

The evidence is insufficient to establish the validity and reliability of computerized tests to evaluate concussions.

Prospective controlled trials are needed to demonstrate the clinical utility of these tests to detect impairment following

concussion.

Wilmoth et al. (2023) conducted a systematic review of the psychometric properties of standard neuropsychological tests

and computerized tools. The review included 103 articles that focused on adolescent or young adult participants with the

Immediate Post-Concussion Assessment and Cognitive Test being the most widely evaluated in 65 of the 103 studies

(63%). There were 13 studies that evaluated a hybrid battery, with both computerized cognitive and traditional

neuropsychological tests. Risk of bias for most studies (n = 76) indicated a moderate risk of bias, while two studies had a

high risk of bias. The authors reported that test-retest reliability estimates ranged from 0.14 to 0.93 for computerized tools

and 0.02 to 0.95 for standard neuropsychological tests with the strongest correlations on processing speed tasks for both

modalities and that reliability was improved with a 2-factor model (processing speed and memory). The authors also

reported that sensitivity to decreased cognitive performance within 72 hours of injury ranged from 45%-93% for

computerized tools and 18%-80% for standard neuropsychological tests and that the method for classifying cognitive

decline affected sensitivity estimates. The authors concluded that combining computerized tools and standard

neuropsychological tests with the strongest psychometric performance provided the greatest value in clinical assessment.

Limitations included common methodological processes (such as use of convenience samples, limited controls for

confounding factors, and unreported effect sizes), protocol deviations, non-standardized instructions, homogeneity of the

athletic participants, continued development of cognitive functions during adolescents that may impact long test-retest

intervals, and the heterogeneity of the standard neuropsychological test batteries, and methods used to classify

impairment. Studies by Broglio (2018), Hang (2015), MacDonald (2015), McCrory (2017), Nelson (2016), and

Weissberger (2017) are included in this systematic review.

Ivins et al. (2022) completed an initial psychometric analysis of the Brain Gauge (BG) personal computer-based test

battery to evaluate its potential use for evaluating patients with acute mild traumatic brain injury (mTBI). The study

participants were 73 military service members (SM) who were assessed within 7 days of their injury at military medical

treatment facilities (emergency department (30.1%), primary care (41.1%) or a TBI specialty clinic (28.8%) and 100

healthy service members as a control group. Prior to completing the BG, participants were administered a demographic

and military questionnaire, the Neurobehavioral Symptom Inventory (NSI), a PTSD Checklist (PCL-5), and a Patient

Health Questionnaire (PHQ-9). The authors reported that SMs with mTBI had statistically significant worse performance

on both BG Reaction Time (RT) tests and the Sequential Amplitude Discrimination test as well as having a significantly

lower whole-battery composite. The authors stated that, while particular subtests of BG are sensitive to the effects of

acute mTBI, there was questionable clinical utility of these scores and that the mTBI group performed worse on some

tests, than the control group. The authors noted that the base rate analysis revealed that a minority of those with mTBI

had multiple scores at or near potentially clinically meaningful performance thresholds, contradicting the very high

diagnostic accuracy statistics published by BG’s developers which raised concerns about the use of an aggregate score

from the BG test battery. Limitations of the study include the small sample size, the delay of up to 7 days post injury which

may have influenced results due to possible cognitive recovery that had occurred and the inclusion of only SMs in the

study. The authors concluded that their study did find that SMs with acute mTBI on average performed worse than healthy

control SMs on the BG Cortical Metric Symptom Score, the BG RT tests and the Sequential Amplitude Discrimination test

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but that the results also demonstrated that overall, BG does not distinguish mTBI cases from controls at a clinically

meaningful rate, and not nearly at the rates previously reported in the literature.

In a prospective longitudinal observational cohort study, Takagi et al. (2019) examined whether cognitive functioning

(measured by CogSport) has prognostic value for predicting rapid versus slow recovery. Data were collected at 1-4, 14-,

and 90-days post-injury. Eligible children were aged ≥ 5 and < 18 years presenting to the Emergency Department having

sustained a concussion within 48 hours. Concussion was defined according to the Zurich/Berlin Consensus Statement on

Concussion in Sport. Dependent variables were reaction times and error rates on the CogSport Brief Battery. In total, 220

cases were analyzed: 98 in a rapid recovery group (asymptomatic at 14 days post-injury, mean age 11.5 [3.2], 73.5%

male) and 122 in a slow recovery group (symptomatic at 14 days post-injury, mean age 12.0 [3.1], 69.7% male).

Longitudinal GEE analyses modeled the trajectories of both mean log10-transformed reaction time and error rates

between groups over time (1-4, 14 and 90 days). Both group main and interaction (time by group) terms for all models

were non-significant (p > .05). The authors concluded that cognitive functioning, measured by CogSport and assessed

within 1-4 days of concussion, does not predict prolonged recovery in a pediatric sample. Further, there were no

significant group differences at any time point. The authors stated that considering the widespread use and promotion of

Computerized neuropsychological tests (CNTs), it is important that clinicians understand the significant limitations of the

CogSport battery.

Ivins et al. (2019) assessed the agreement between the following four brief computerized neurocognitive assessment

tools by comparing rates of low scores: Automated Neuropsychological Assessment Metrics (ANAM); CogState, also

known as CogSport or Axon Sports; Central Nervous System Vital Signs (CNSVS); and Immediate Post-concussion

Assessment and Cognitive Test (ImPACT). Four hundred and six US Army service members (SMs) with and without

acute mTBI completed two randomly assigned CNTs with order of administration also randomly assigned. A base rate

analysis was performed for each CNT to determine the proportions of SMs in the control and mTBI groups who had

various numbers of scores that were 1.0 +, 1.5 +, and 2.0 + standard deviations below the normative mean. These results

were used to identify a hierarchy of low score levels ranging from poorest to least poor performance. The agreement was

compared between every low score level from each CNT pair administered to the SMs. More SMs in the mTBI group had

low scores on all CNTs than SMs in the control group. As performance worsened, the association with mTBI became

stronger for all CNTs. Most if not all SMs who performed at the worst level on any given CNT also had low scores on the

other CNTs they completed but not necessarily at an equally low level. The authors indicated that the psychometric

comparability and clinical utility of these CNTs are not well understood and until such studies are done it will not be

possible to make any judgments about which CNT, if any, is superior to the others. The authors state that until more

evidence emerges, these CNTs should be used cautiously and only as one source of information from among many other

types of clinical assessments. None of them should be used as a definitive or standalone diagnostic tool. An important

limitation of this study is that there were relatively small numbers of SMs in each CNT pair who performed at the poorest

levels so the results of this study should be treated as preliminary. Another limitation is that the data is from military

service members and these findings may not be generalizable to other populations such as high school and college

athletes.

Cole et al. (2018) investigated the validity of four computerized neurocognitive assessment tools (NCATs): the ANAM4,

CNS-VS, CogState, and ImPACT. Two NCATs were randomly assigned and a battery of traditional neuropsychological

(NP) tests administered to 272 healthy control active-duty service members and to 231 service members within 7 days of

an mTBI. Analyses included correlations between NCAT, and the NP test scores to investigate convergent and

discriminant validity, and regression analyses to identify the unique variance in NCAT and NP scores attributed to group

status. Effect sizes (Cohen's f2) were calculated to guide interpretation of data. Only 37 (0.6%) of the 5,655 correlations

calculated between NCATs and NP tests are large. The majority of correlations are small, with no clear patterns

suggestive of convergent or discriminant validity between the NCATs and NP tests. Though there are statistically

significant group differences across most NCAT and NP test scores, the unique variance accounted for by group status is

minimal with effect sizes indicating small to no meaningful effect. The authors concluded that although the results are not

overly promising for the validity of the four NCATs investigated, traditional methods of investigating psychometric

properties may not be appropriate for computerized tests.

The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of

Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline

Workgroup and developed a guideline based on a previous systematic review of the literature (Lumba-Brown et al., 2018)

to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the

diagnosis, prognosis, and management/treatment of pediatric mTBI. The CDC guideline included the recommendations

on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (i.e.,

must, should, or may) based on confidence in the evidence. Regarding computerized cognitive testing, the CDC stated

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that health care professionals may use validated, age-appropriate computerized cognitive testing in the acute period of

injury as a component of the diagnosis of mTBI (moderate; level C).

In a consensus statement, the

International Conference on Concussion in Sport states that the use of

neuropsychological testing (NP) contributes significant information in concussion assessment. Brief computerized

cognitive evaluation tools are a commonly utilized component of these assessments worldwide given the logistical

limitation in accessing trained neuropsychologists. However, it should be noted that these are not substitutes for complete

NP assessment. For children, it is recommended that age-specific validated symptom-rating scales be used in sport-

related concussion (SRC) assessment, and further research is required to establish the role and utility of computerized

NP testing in this age group. The consensus statement suggests that baseline testing may be useful but is not necessary

for interpreting post-injury scores (McCrory et al., 2017).

Farnsworth et al. (2017) analyzed reliability data for computerized neurocognitive tests (CNTs) using meta-analysis and

examined moderating factors that may influence reliability. Studies were included in the meta-analysis if they met all of the

following criteria: used a test-retest design, involved at least 1 CNT, provided sufficient statistical data to allow for effect-

size calculation, and were published in English. Two independent reviewers investigated each article to assess inclusion

criteria. Eighteen studies involving 2674 participants were retained. Intraclass correlation coefficients were extracted to

calculate effect sizes and determine overall reliability. Moderator analyses were conducted to evaluate the effects of the

length of the test-retest interval, intraclass correlation coefficient model selection, participant demographics, and study

design on reliability. Heterogeneity was evaluated using the Cochran Q statistic. The proportion of acceptable outcomes

was greatest for the Axon Sports CogState Test (75%) and lowest for the Immediate Post-Concussion Assessment and

Cognitive Testing (ImPACT) (25%). Moderator analyses indicated that the type of intraclass correlation coefficient model

used significantly influenced effect-size estimates, accounting for 17% of the variation in reliability. The authors concluded

that the Axon Sports CogState Test, which has a higher proportion of acceptable outcomes and shorter test duration

relative to other CNTs, may be a reliable option; however, future studies are needed to compare the diagnostic accuracy

of these instruments (The Nakayama et al. (2014) study which was previously cited in this policy, is included in the

Farnsworth et al. (2017) meta-analysis).

Gaudet and Weyandt (2017) conducted a systematic review of existing research investigating Immediate Post-

Concussion and Cognitive Testing (ImPACT) and the prevalence of invalid baseline results including the effectiveness of

ImPACT's embedded invalidity indicators in detecting suspect effort. Preferred Reporting Items for Systematic Reviews

and Meta-Analyses guidelines were followed in order to systematically structure a search across four databases and

analysis of studies that presented data related to the prevalence of invalid performance and/or the effectiveness of

ImPACT's embedded invalidity indicators. A total of 17 studies included prevalence rates of invalid performances or

examined the effectiveness of ImPACT's invalidity indicators. Of the 17 studies, 12 included prevalence rates of invalid

baseline results; and across this group of studies (after removing an outlier), the weighted prevalence rate of invalid

baseline results was 6%. Four of the 17 studies examined the effectiveness of ImPACT's embedded invalidity indicators.

ImPACT's embedded invalidity indicators correctly identified suboptimal effort in approximately 80% of individuals

instructed to perform poorly and avoid detection ('coached') or instructed to perform poorly ('naïve'). According to the

authors, these findings raise a number of issues pertaining to the use of ImPACT. Invalid performance incidence may

increase with large group versus individual administration, use in nonclinical settings, and among those with Attention

Deficit-Hyperactivity Disorder or learning disability. Additionally, the older desktop version of ImPACT appears to be

associated with a higher rate of invalid performances than the online version. Although ImPACT's embedded invalidity

indicators detect invalid performance at a rate of 6% on average, known group validity studies suggest that these

measures miss invalid performance approximately 20% of the time when individuals purposefully underperform.

Nelson et al. (2017) evaluated the reliability and validity of three computerized neurocognitive assessment tools

(Automated Neuropsychological Assessment Metrics [ANAM], Defense Automated Neurobehavioral Assessment [DANA],

and Immediate Post-Concussion Assessment and Cognitive Testing [ImPACT]) for assessing mTBI. The study included

mTBI (n = 94) and matched trauma control (n = 80) subjects recruited from a level I trauma center emergency department

(ED) completed symptom and neurocognitive assessments within 72 hours of injury and at 15- and 45-days post-injury.

Concussion symptoms were also assessed via phone at 8 days post-injury. Computerized neurocognitive assessment

tools (CNTs) did not differentiate between groups at any time point. Roughly a quarter of stability coefficients were over

.70 across measures and test-retest intervals in controls. The authors concluded that the CNTs evaluated, developed, and

widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus

other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in

sport-related concussion studies. According to the authors, nonspecific injury factors, and other characteristics common in

ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs

for assessing mTBI in this patient population. The authors indicated that this investigation had several limitations. First,

subjects were evaluated in a laboratory setting within 72 hr. of injury; thus, it is possible that stronger group differences in

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clinical assessment measures would have been found had subjects been assessed more acutely (such as within the ED).

Second, the study design (i.e., assignment of two of three CNTs to each subject) and presence of loss to follow-up (16%

at 45 days post-injury) contributed to smaller sample sizes (< 50) for some CNT measures and at some time points.

In a systematic review, Alsalaheen et al. (2016) assessed the literature on the reliability of the Immediate Post-

Concussion Assessment and Cognitive Testing (ImPACT). Ten studies that met the inclusion criteria were included in the

review. With the exception of processing speed, all composite scores consistently exhibited poor to moderate reliability.

When considering 2 time points, participants who were misclassified as experiencing a "reliable change" in any score

ranged between 5% and 26% for verbal memory, 2.2% and 19.6% for visual memory, 4% and 24% for processing speed,

and 4% and 23.2% for reaction time. The authors concluded that the majority of ImPACT composite scores did not

consistently demonstrate good reliability. According to the authors, clinicians should be cautious when ImPACT is used as

a criterion for medical clearance to return to play after concussion. Because of its widespread use in concussion-related

clinical research, researchers must exercise due diligence when utilizing ImPACT to evaluate outcomes after concussion

or to validate other outcome measures. (Cited in Farnsworth et al., 2017)

Kontos et al. (2014) performed a meta-analysis assessing the effects of sport-related concussion as measured by

computerized neurocognitive tests (NCT) 1-week post injury. Thirty-seven studies involving 3960 participants between

2000 and 2011 were included. Code substitution, visual memory, processing speed, and memory tasks demonstrated

negative effects for concussion. Younger adolescents had lower NCT performance than older adolescents and college

aged athletes. ImPACT studies demonstrated a negative effect for concussion as did those involving contact sports. The

authors found that computerized neurocognitive testing results suggest athletes suffer impairments within one week of a

concussion. Several factors such as age, type of neurocognitive test, and test administrator may lead to more pronounced

impairments. The authors indicated that no single tool can or should be used to measure the effect of concussion.

Instead, clinicians and researchers should adopt a comprehensive approach to assessing this injury.

Echemendia et al. (2013) critically reviewed the literature from the past 12 years regarding key issues in sports-related

neuropsychological assessment of concussion. Based on the review of the literature, the authors concluded that

traditional and computerized neuropsychological tests are useful in the evaluation and management of concussion. A brief

cognitive evaluation tools cannot substitute for formal neuropsychological assessment. According to the authors, there is

insufficient evidence to recommend the widespread routine use of baseline neuropsychological testing.

Baseline Neuropsychological Testing for Concussion

There is insufficient evidence to indicate that the use of baseline neuropsychological testing in athletes or other individuals

alters risk from concussion. There is insufficient evidence that baseline tests influence physician decision-making or

outcomes of treatment of concussion.

D’Alessio et al. (2024) conducted a case-control study with 6495 middle and high school–aged student-athletes (average

age 14.9 +/- 1.3 years, 59.4% male) in a single county in Ohio who completed a baseline Immediate Post-Concussion

Assessment and Cognitive Testing (ImPACT) test between ages 10 and 18 years old and who could be linked to the

Child-Household Integrated Longitudinal Data (CHILD) system via a probabilistic matching process to examine the

relationship between individual-level experiences of adversity and baseline test validity of ImPACT. Validity of the first

baseline test (as determined by ImPACT’s built-in validity scoring, age, and home address at the first baseline test) along

with any concussion history and diagnosis of learning or developmental disorders (ADHD, dyslexia, autism) were

extracted from the ImPACT testing records where 435 (6.7%) participants were found to have an invalid test. The authors

reported that social mobility may play an important role in baseline validity and that those with upward social mobility (i.e.,

poverty or neighborhood deprivation in early childhood only) were not different from youth without such experiences;

however, youth with persistent adversity across childhood or downward social mobility had 50% to 72% lower odds of

achieving a valid baseline test. The authors also reported that maltreatment had no significant effect on test validity. The

authors concluded that certain patterns of adversity may predispose youth to invalid baseline testing scores, potentially

increasing their risk of inappropriate injury management and poor outcomes and that without adequate retesting, youth

with particular patterns of adversity may face compounded disadvantages, both from the adversities themselves and from

inaccurate neurocognitive diagnostic tests. Limitations of the study include the single county design, the use of data

gathered from the child welfare system as children with minoritized racial identities are more likely to be referred or

investigated for maltreatment, the use of program enrollment for the Supplemental Nutrition Assistance Program and the

Temporary Assistance for Needy Families Program may have limited the authors’ understanding of poverty in the study

population, and the use of the mother’s race as a proxy for the child’s race since race is not recorded on birth certificates

in Ohio.

Cosgrave et al. (2023) completed a prospective cohort study with 135 school-aged (15 to 19 years) rugby players from 5

schools to explore whether the Sports Concussion Assessment Tool (SCAT), Cogstate Brief Battery (CBB) and the King-

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Devick test (K-D test) can be used to monitor concussion status through to full recovery. In this study, all participants

completed baseline tests in the preseason where it was found that 61 (45.2%) reported a prior lifetime history of sport

related concussion (SRC) and 64 (48%) participants reported symptoms on their baseline SCAT (mean 3.3; range 1-16)

with the most common symptoms being fatigue/low energy (31%), neck pain (16%) and irritability (14%). The season

consisted of 25 training weeks and 18 games on average across the five teams. During the season, 16 participants

experienced 18 SRCs with 9 (56.3%) of the participants having a prior history of SRC. These participants underwent

weekly post-concussion testing starting within 1-7 days of injury (mean 3.9 days) with the full battery of tests and an

individualized rehabilitation program until recovered. One participant remained symptomatic at 87 days and was referred

to a neurologist. Of the remaining 17 concussions, mean severity was 20 days (range 4-42 days). Participants with SRC

underwent 52 post-concussion CBB assessments with results consistent with clinically assessed recovery status on 27

(51.9%) occasions. The CBB had a false positive rate of 33% and test specificity was 67%. On 7 (13.5%) occasions

participants failed the CBB when clinically they were deemed to be recovered from their concussion. The CBB had a false

negative rate of 58% and test sensitivity was 42%. On 18 (34.6%) occasions participants passed the CBB when clinically

they were deemed not recovered from their concussion. There were 50 post-concussion K-D tests performed that had

results consistent with clinically assessed recovery status on 32 (64%) occasions. The K-D test had a false positive rate of

11% and test specificity was 90%. On 2 (4%) occasions participants failed the K-D when clinically they were deemed to

be recovered from their concussion. The K-D test had a false negative rate of 52% and test sensitivity was 48%. On 16

(32%) occasions participants passed the K-D when clinically they had been deemed not recovered from their concussion.

The authors reported that the CBB and K-D tests were poorly associated with clinical assessment and produced high

false negative rates of 0.58 and 0.52, respectively. The authors concluded that analysis of clinical recovery with CBB and

K-D test revealed a relatively poor ability to accurately monitor concussion status compared to clinical assessment. The

authors stated that their findings suggest that these tools not be used in isolation for monitoring SRC recovery in

adolescents. Limitations of the study include the lack of objective measures of concussion recovery, dependence of

concussion detection on school medical staff, the small sample size and concussion incidence and the lack of a follow-up

comparison of the tests on the participants who did not sustain an SRC.

Tsushima et al. (2019) identified valid, invalid (identified by five embedded Invalidity Indicators), and sandbagging

(identified by three "red flags") results in the ImPACT baseline test scores of 6,346 high school athletes. In addition, the

ImPACT post-concussion scores of 266 athletes who sustained a concussion during the school year were evaluated to

compare the baseline-to-post concussion changes of valid versus a combined group of invalid and sandbagging scorers.

There were 3,299 (51.99%) athletes who had valid baseline scores, 269 (4.24%) had invalid scores, and 3,009 (47.42%)

had sandbagging scores. (There were 231 who obtained both invalidity and sandbagging scores.) The overall difference

in baseline-to-post concussion changes between the valid scorers and the combined group of invalid and sandbagging

scorers was statistically significant. The authors stated that the high rate of athletes who had invalid and sandbagging

scores raised concern that the underperformance of baseline testing occurs more commonly than is probably realized by

those who utilize computerized neuropsychological testing with high school athletes. Accordingly, efforts are needed to

improve test administration procedures so that maximal attention and effort can be maintained among the test takers.

According to the authors, increased caution is called for in employing the baseline-to-post concussion paradigm when

return-to-play decisions are made.

Abeare et al. (2018) assessed the prevalence of invalid performance on baseline neurocognitive testing using embedded

measures within computerized tests and individually administered neuropsychological measures and examined the

influence of incentive status and performance validity on neuropsychological test scores. A total of 83 collegiate football

athletes completing their preseason baseline assessment within the University's concussion management program and a

control group of 140 non-athlete students were included in the study. The cross-sectional design of the study was based

on differential incentive status: motivated to do poorly to return to play more quickly after sustaining a concussion

(athletes) versus motivated to do well due to incentivizing performance (students). The main measures of the study

included Immediate Post-Concussion and Cognitive Testing (ImPACT), performance validity tests, and measures of

cognitive ability. Half of the athletes failed at least 1 embedded validity indicator within ImPACT (51.8%), and the

traditional neuropsychological tests (49.4%), with large effects for performance validity on cognitive test scores, incentive

status, and the combination of both factors on measures of attention and processing speed. The authors concluded that

invalid performance on baseline assessment is common (50%), consistent across instruments (ImPACT or

neuropsychological tests) and settings (one-on-one or group administration), increases as a function of incentive status

(risk ratios: 1.3-4.0) and results in gross underestimates of the athletes' true ability level, complicating the clinical

interpretation of the postinjury evaluation and potentially leading to premature return to play.

In a retrospective, cross-sectional study, Abeare et al. (2018) assessed the prevalence of invalid performance on baseline

testing and assessed whether the prevalence varies as a function of age and validity indicator. Participants included 7897

consecutively tested equivalently proportioned male and female athletes aged 10 to 21 years, who completed baseline

neurocognitive testing for the purpose of concussion management. Baseline assessment was conducted with the

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Immediate Post-concussion Assessment and Cognitive Testing (ImPACT). Base rates of failure on published ImPACT

validity indicators were compared within and across age groups. Hypotheses were developed after data collection but

prior to analyses. Of the 7897 study participants, 4086 (51.7%) were male, mean (SD) age was 14.71 years, 7820

(99.0%) were primarily English speaking, and the mean (SD) educational level was 8.79 years. The base rate of failure

ranged from 6.4% to 47.6% across individual indicators. Most of the sample (55.7%) failed at least 1 of 4 validity

indicators. The base rate of failure varied considerably across age groups (117 of 140 [83.6%] for those aged 10 years to

14 of 48 [29.2%] for those aged 21 years), representing a risk ratio of 2.86. The authors indicated that the results for base

rate of failure were surprisingly high overall and varied widely depending on the specific validity indicator and the age of

the examinee. The strong age association, with 3 of 4 participants aged 10 to 12 years failing validity indicators, suggests

that the clinical interpretation and utility of baseline testing in this age group is questionable. According to the authors,

these findings underscore the need for close scrutiny of performance validity indicators on baseline testing across age

groups.

Computerized Cognitive Testing Such as Cognivue, Mindstreams, BrainCare, and

QbTest

Available clinical trials fail to document a beneficial effect of computerized cognitive testing on long-term clinical

outcomes. The evidence is insufficient to establish the validity of computerized cognitive testing compared with traditional

tests for the assessment of dementia and cognitive impairment.

McMurray et al (2024) conducted a study to assess the validity, reliability, and applicability of a short digitally administered

test, the BrainEx SCREEN, as a screening tool for mild cognitive impairment (MCI) in an aging population in primary care

settings. The study included 147 asymptomatic adults aged 55 or older from five primary care Family Health Teams

(FHTs). Participants included health care practitioners, patients and FHT administrative executives with no history of MCI

or diagnosis of dementia. Each participant underwent the BrainEx SCREEN, the Quick Mild Cognitive Impairment (QMCI)

screen, and the Geriatric Anxiety Scale–10 in a minimum of two screening sessions spaced three months apart with a

maximum of four screening sessions over a year. It was noted that the emergence of the COVID-19 pandemic resulted in

the some of the assessments being done virtually while others were done face-to-face. The authors reported that their

study found that the SCREEN’s longer administration time and complex scoring algorithm had challenges such as the

internal consistency being below the acceptable threshold and that the test-retest reliability had limitations with moderate

intraclass correlation coefficient and inadequate k values. The authors also reported that sensitivity and specificity were

consistent between cross-tabulation and discrepant analysis. Limitations noted by the authors included the demographic

homogeneity (65.3% female, well-educated participants), the absence of a comprehensive gold standard for MCI

diagnosis, and financial constraints that limited the inclusion of confirmatory neuropsychological testing. Other limitations

included the small study population, and the absence of verbal fluency testing and memory tests. The authors concluded

that the SCREEN did not meet the necessary criteria for an optimal MCI screening tool in a primary care setting due to the

longer administration time and lower reliability.

Hayes (2023) published an Evidence Analysis Research Brief on the Cognitrax (CNS Vital Signs LLC) neurocognitive

assessment battery indicated for diagnosing and evaluating cognitive, behavioral, and socioemotional functioning to

detect neurocognitive disorders. The battery consists of four subtests: finger tapping, verbal memory, symbol digit coding,

and the continuous performance test. These tests are utilized to evaluate mental processes, including simple motor

performance, attention, memory, and processing speed. A patient’s neurocognitive function is computed by tracking the

number of correct and incorrect responses as well as reaction time with each of the four subsets. In their brief, Hayes

found that there currently is not enough published peer-reviewed literature to evaluate the evidence related to Cognitrax

for assessment of behavioral and cognitive changes in a full assessment as they were not able to identify any studies that

evaluated this assessment battery.

Bellato et al. (2023) conducted a systematic review and meta-analysis of 15 studies that evaluated accuracy and clinical

utility of the QbTest, a computerized cognitive test that is intended to support the clinical assessment of ADHD. There was

a total of 2,058 participants (48.6% with ADHD, 53% adults, 20% less than 10 years of age) included in the studies. The

authors noted that nine of the 15 studies used QbTest+ (for adolescents > 12 years old, and adults), one used QbTest 6–

12 (children ≤12 years old), three used both QbTest+ and QbTest 6–12 (since they had mixed samples of children,

adolescents, and adults), one used QbCheck (conducted at participants’ home, based on both QbTest+ and QbTest 6–12

due to wide age range of the sample), and one used QbMini (for preschoolers). The risk analysis showed potential risk of

bias in patient selection in seven of the studies. The authors reported that the QbTest total scores showed acceptable,

rather than good, sensitivity and specificity in the nine studies that reported both sensitivity and specificity, while

subscales showed low-to-moderate sensitivity and moderate-to-good specificity. The authors also reported that the pooled

Area under the Receiver Operating Characteristics Curve (AUC) showed moderate-to-acceptable discriminative ability.

Subgroup analyses were not able to be conducted by the authors due to the scarcity of the studies. Limitations of the

study include the heterogeneity of the versions of the QbTest used, age groups included in the studies, patient selection

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criteria and study design, the reporting parameters and comparison groups included in the studies, the homogeneity of the

high-income countries included in the study, and the small number of studies available for inclusion. The authors

concluded that the QbTest scores are not sufficiently accurate in discriminating between ADHD and non-ADHD clinical

cases when they are used on their own. The authors recommended that the QbTest should not be used as a stand-alone

screening or diagnostic tool or as a triage system for accepting individuals on the waiting list for clinical services; however,

when the QbTest is used as an adjunct to support a full clinical assessment, it can produce efficiencies in the assessment

pathway and reduce the time to diagnosis. This systematic review included the Hollis 2018 and Brunkhorst-Kanaan 2020

studies previously included in this policy.

In a systematic review and meta-analysis of diagnostic tests for the screening of mild cognitive impairment (MCI) and

dementia, Chan et al. (2022) included 90 studies with 22, 567 participants to evaluate diagnostic performance among

different types of digital drawing tests and paper-and-pencil drawing tests. Seventy-six of the included studies included

participants with MCI or dementia in an outpatient clinic or from the community while the rest of the studies recruited

participants in a hospital or long-term care setting. The digital drawing tests included in their review and analysis included

the digital clock drawing test (CDT), digital pentagon drawing test, digital Rey-Osterrieth complex figure (ROCF), digital

tree drawing test, digital house drawing test, and digital spiral test while the paper-and-pencil drawing tests included the

CDT, pentagon drawing test, cube drawing test, and ROCF. Six of the studies used digital CDT and 80 of the studies

used paper-and-pencil CDT. The primary outcome of the study was the diagnostic performance of the CDT for the

screening of MCI and dementia and the secondary outcome was the diagnostic performance of the other types of drawing

tests. The authors reported that the performances of the digital and paper-and-pencil pentagon drawing tests were

comparable in the screening of dementia, but that the digital CDT demonstrated better sensitivity and specificity

diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable

performance with paper-and-pencil formats. Limitations of this study include the lack of head-to-head comparisons, and

that the number of studies to compare diagnostic performance of drawing tests are limited. The authors stated that the

benefits of digital drawing tests may be stronger if there were more studies available for this meta-analysis.

Romero-Garcia et al. (2022) completed a single-center, prospective cohort study to assess if cognitive impairments would

be apparent in a young and high functioning cohort and that app-based cognitive screening would complement traditional

neuropsychological assessments. Their study included 17 patients with diffuse giiomas who completed a

neuropsychological battery of tests that took 2 -3 hours to complete and the OCS-BRIDGE assessment, an app-based

touchscreen assessment that could be completed in 30 minutes. The traditional neuropsychological assessment was

administered pre-operatively while the OCS-BRIDGE was administered pre- and post-operatively at the 3- and 12-month

follow-ups. The authors reported that the traditional assessment showed that 79% of participants had an impairment in at

least one domain, and an average of 2.88 cognitive impairments per participant before surgery, and that, after surgery, all

but one participant had at least one impairment with a mean of 4.5 impairments per participants. The OCS-BRIDGE

touchscreen assessment showed that 59% of participants had an impairment in at least one domain with a mean of 0.94

impairments per participant before surgery while longitudinal post-operative changes showed that 44% had a reduced

number of impairments by their last assessment, 25% had the same, and 31% showed an increased number of

impairments. Overall, the traditional neuropsychological tests detected 44 preoperative impairments among the 17

participants in the four combined domains of attention, memory, verbal skills, and non-verbal skills. OCS-BRIDGE

detected 13 impairments and 28 possible impairments pre-operatively The authors recognized that the traditional

assessment using multiple items across the difficulty range proved more sensitive than the brief touchscreen assessment;

however, they also noted that the capacity of the screening app to capture reaction times enhanced its sensitivity in the

area of non-verbal function. The authors concluded that a combined approach, using traditional assessment in those

areas where brief screening, may be less sensitive, and OCS-BRIDGE style measures for reaction time and perceptual

tasks may be most effective and recommended robust, objective, and accessible assessment across multiple centers.

Limitations of the study include the small sample size and single-center design, logistical and technical limitations to the

assessments, heterogeneity of tumor location, size and treatment and the potential for practice effects due to reuse of the

cognitive assessment tools.

A statistical analysis by Ye et al. (2022) was performed to evaluate BrainCheck, a computerized cognitive testing battery,

for its diagnostic accuracy and ability to distinguish the severity of cognitive impairment. A total of 99 participants

diagnosed with dementia, mild cognitive impairment (MCI), or normal cognition (NC) completed the BrainCheck battery.

Statistical analyses compared participant performances on BrainCheck based on their diagnostic group. BrainCheck

battery performance showed differences between the NC, MCI, and dementia groups, achieving 88% or higher sensitivity

and specificity (i.e., true positive and true negative rates) for separating dementia from NC, and 77% or higher sensitivity

and specificity in separating the MCI group from the NC and dementia groups. Three-group classification found true

positive rates of 80% or higher for the NC and dementia groups and true positive rates of 64% or higher for the MCI

group. The authors concluded that BrainCheck was able to distinguish between diagnoses of dementia, MCI, and NC,

providing a potentially reliable tool for early detection of cognitive impairment. A small sample size makes it difficult to

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decide whether these conclusions can be generalized to a larger population. Further research with randomized controlled

trials is needed to validate these findings.

Chan et al. (2021) performed a systematic review to evaluate the diagnostic performance of digital cognitive tests for mild

cognitive impairment (MCI) and dementia in older adults. Literature searches were systematically performed in the OVID

databases. Validation studies that reported the diagnostic performance of a digital cognitive test for MCI or dementia were

included. The main outcome was the diagnostic performance of the digital test for the detection of MCI or dementia. A

total of 56 studies with 46 digital cognitive tests were included in this study. Most of the digital cognitive tests were shown

to have comparable diagnostic performances with the paper-and-pencil tests. Twenty-two digital cognitive tests showed a

good diagnostic performance for dementia, with a sensitivity and a specificity over 0.80, such as the Computerized Visuo-

Spatial Memory test and Self-Administered Tasks Uncovering Risk of Neurodegeneration. Eleven digital cognitive tests

showed a good diagnostic performance for MCI such as the Brain Health Assessment. However, all the digital tests only

had a few validation studies to verify their performance. The authors concluded that digital cognitive tests showed good

performances for MCI and dementia, and that the digital test can collect digital data that is far beyond the traditional ways

of cognitive tests. Further research with randomized controlled trials is needed to validate these findings.

An observational study by Rubin et al. (2021) was performed to determine the feasibility of implementing an iPad-based

cognitive impairment screening tool, the psychometric properties of the tool, and predictors of cognitive impairment among

adults seeking HIV care. A convenience sample of participants completed Brain Baseline Assessment of Cognition and

Everyday Functioning (BRACE), which included (1) Trail Making Test Part A, measuring psychomotor speed; (2) Trail

Making Test Part B, measuring set-shifting; (3) Stroop Color, measuring processing speed; and (4) the Visual–Spatial

Learning Test. Global neuropsychological function was estimated as mean T score performance on the 4 outcomes.

Impairment on each test or for the global mean was defined as a T score ≤ 40. Subgroups of participants repeated the

tests 4 weeks or > 6 months after completing the first test to evaluate intrapersonal test–retest reliability and practice

effects (improvements in performance due to repeated test exposure). An additional subgroup completed a lengthier

cognitive battery concurrently to assess validity. Relevant factors were abstracted from electronic medical records to

examine predictors of global neuropsychological function. The study population consisted of 404 people with HIV (age:

mean 53.6 years; race: 332/404, 82% Black; 34/404, 8% White, 10/404, 2% American Indian/Alaskan Native; 28/404, 7%

other and 230/404, 58% male; 174/404, 42% female) of whom 99% (402/404) were on antiretroviral therapy. Participants

completed BRACE in a mean of 12 minutes (SD 3.2), and impairment was demonstrated by 34% (136/404) on Trail

Making Test A, 44% (177/404) on Trail Making Test B, 40% (161/404) on Stroop Color, and 17% (67/404) on Visual-

Spatial Learning Test. Global impairment was demonstrated by 103 out of 404 (25%). Test–retest reliability for the subset

of participants (n = 26) repeating the measure at 4 weeks was 0.81 and for the subset of participants (n = 67) repeating

the measure almost 1 year later (days: median 294, IQR 50) was 0.63. There were no significant practice effects at either

time point (p = .20 and p = .68, respectively). With respect for validity, the correlation between global impairment on the

lengthier cognitive battery and BRACE was 0.63 (n = 61; p < .001), with 84% sensitivity and 94% specificity to impairment

on the lengthier cognitive battery. The authors concluded that they were able to successfully implement BRACE and

estimate cognitive impairment burden in the context of routine clinic care. BRACE was also shown to have good

psychometric properties. This easy-to-use tool in clinical settings may facilitate the care needs of people with HIV as

cognitive impairment continues to remain a concern in people with HIV. Further research with randomized controlled trials

is needed to validate these findings.

Wilson et al. (2021) performed a systematic review of literature to evaluate the benefits, limitations, and validity of

computerized neuropsychological assessment devices (CNADs) in the evaluation of HIV-associated neurocognitive

disorder (HAND). Following a comprehensive search, the abstracts of relevant articles were compiled and then reviewed

for the use of digital neuropsychological testing in the setting of HIV. The articles that met these criteria were read, and

their reference lists further examined to compile a more inclusive review. The review was limited to peer-reviewed

English-language journals published within the past 20 years, with no other restrictions, such as sample size or analysis

type. Eight CNADs that have undergone validity testing in the setting of HIV were identified and included in the review.

The studies included CNADs modeled after traditional testing batteries as well as non-traditional cognitive batteries with

advanced technology features including simulated or virtual realities and quick, daily mobile phone assessments, which

were reviewed. This review suggests that these computerized neuropsychological assessment devices remain in the early

stages of development. The authors concluded that these digital batteries do not have the ability to supplant gold standard

neuropsychological tests in screening for HAND. However, many have the potential to become effective clinical screening

tools. This review reveals most of these validity studies do not employ large enough sample sizes (fewer than 100) to

conclusively determine their ability to detect HAND, creating a degree of uncertainty in external validity. A small sample

size makes it difficult to decide whether these conclusions can be generalized to a larger population. The findings of this

study need to be validated by well-designed studies. Further investigation is needed before clinical usefulness of this

procedure is proven.

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Cahn-Hidalgo et al. (2020) determined the cut-off scores for classification of cognitive impairment and assessed Cognivue

safety and efficacy in a validation study. Adults (age 55-95 years) at risk for age-related cognitive decline or dementia

were invited via posters and email to participate in two cohort studies conducted at various outpatient clinics and assisted-

and independent-living facilities. In the cut-off score determination study (n = 92), optimization analyses by positive

percent agreement (PPA) and negative percent agreement (NPA), and by accuracy and error bias were conducted. In the

clinical validation study (n = 401), regression, rank linear regression, and factor analyses were conducted. Participants in

the clinical validation study also completed other neuropsychological tests. For the cut-off score determination study, 92

participants completed St. Louis University Mental Status (SLUMS, reference standard) and Cognivue tests. Analyses

showed that SLUMS cut-off scores of < 21 (impairment) and > 26 (no impairment) corresponded to Cognivue scores of

54.5 (NPA = 0.92; PPA = 0.64) and 78.5 (NPA = 0.5; PPA = 0.79), respectively. Therefore, conservatively, Cognivue

scores of 55-64 corresponded to impairment, and 74-79 to no impairment. For the clinical validation study, 401

participants completed ≥ 1 testing session, and 358 completed 2 sessions 1-2 wk. apart. Cognivue classification scores

were validated, demonstrating good agreement with SLUMS scores (weighted κ 0.57; 95%CI: 0.50-0.63). Reliability

analyses showed similar scores across repeated testing for Cognivue (R 2 = 0.81; r = 0.90) and SLUMS (R 2 = 0.67; r =

0.82). Psychometric validity of Cognivue was demonstrated vs. traditional neuropsychological tests. Scores were most

closely correlated with measures of verbal processing, manual dexterity/speed, visual contrast sensitivity,

visuospatial/executive function, and speed/sequencing. The investigators concluded that Cognivue scores ≤ 50 avoid

misclassification of impairment, and scores ≥ 75 avoid misclassification of un-impairment. According to the investigators,

this validation study demonstrates good agreement between Cognivue and SLUMS; superior reliability; and good

psychometric validity. A limitation of these studies is the use of a single reference standard, SLUMS. Longitudinal follow-

up studies are needed to evaluate the ability of Cognivue to monitor cognitive deterioration over time.

Groppell et al., (2019) determined the accuracy and validity of BrainCheck Memory as a diagnostic aid for age-related

cognitive impairment, as compared against physician diagnosis and other commonly used neurocognitive screening tests,

including the Saint Louis University Mental Status (SLUMS) exam, the Mini-Mental State Examination (MMSE), and the

Montreal Cognitive Assessment (MoCA). A total of 583 volunteers over the age of 49 were tested from various community

centers and living facilities. The volunteers were divided into five cohorts: a normative population and four comparison

groups for the SLUMS exam, the MMSE, the MoCA, and physician diagnosis. Each comparison group completed their

respective assessment and BrainCheck Memory. A total of 398 subjects were included in the normative population. A total

of 84 participants were in the SLUMS exam cohort, 51 in the MMSE cohort, 35 in the MoCA cohort, and 18 in the

physician cohort. BrainCheck Memory assessments were significantly correlated to the SLUMS exam, with coefficients

ranging from .5 to .7. Correlation coefficients for the MMSE and BrainCheck and the MoCA and BrainCheck were also

significant. Of the 18 subjects evaluated by a physician, 9 (50%) were healthy, 6 (33%) were moderately impaired, and 3

(17%) were severely impaired. A significant difference was found between the severely and moderately impaired subjects

and the healthy subjects (p = .02). The investigators found that the BrainCheck Memory composite score showed stronger

correlations with the standard assessments as compared to the individual BrainCheck assessments. Receiver operating

characteristic (ROC) curve analysis of this composite score found a sensitivity of 81% and a specificity of 94%. The

investigators concluded that BrainCheck Memory provides a sensitive and specific metric for age-related cognitive

impairment in older adults, with the advantages of a mobile, digital, and easy-to-use test. According to the authors, some

participants were unable to complete BrainCheck’s entire battery of assessments. While this was accounted for during the

analysis, the missing data may have limited statistical power. The investigators also indicated that due to the study’s small

sample size, more research is needed to compare and validate BrainCheck against physician diagnosis.

Aslam et al. (2018) conducted a systematic review to determine whether automated computerized tests accurately identify

patients with progressive cognitive impairment and, if so, to investigate their role in monitoring disease progression and/or

response to treatment. Six electronic databases were searched from January 2005 to August 2015 to identify papers for

inclusion. Studies assessing the diagnostic accuracy of automated computerized tests for mild cognitive impairment (MCI)

and early dementia against a reference standard were included. Where possible, sensitivity, specificity, positive predictive

value, negative predictive value, and likelihood ratios were calculated. The Quality Assessment of Diagnostic Accuracy

Studies tool was used to assess risk of bias. Sixteen studies assessing 11 diagnostic tools for MCI and early dementia

were included. No studies were eligible for inclusion in the review of tools for monitoring progressive disease and

response to treatment. The overall quality of the studies was good. However, the wide range of tests assessed, and the

non-standardized reporting of diagnostic accuracy outcomes meant that statistical analysis was not possible. The authors

concluded that some tests have shown promising results for identifying MCI and early dementia. However, concerns over

small sample sizes, lack of replicability of studies, and lack of evidence available make it difficult to make

recommendations on the clinical use of the computerized tests for diagnosing, monitoring progression, and treatment

response for MCI and early dementia.

Racine et al. (2016) conducted a study that included 469 late middle-aged participants from the Wisconsin Registry for

Alzheimer's Prevention (mean age 63.8 ±7 years at testing; 67% female; 39% APOE4 +) to evaluate whether

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computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology

in people at risk for AD. The study examined relationships between a CogState abbreviated battery (CAB) of seven tests

and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive

impairment index, cognitive impairment status (determined by consensus review), and biomarkers for amyloid and

tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein). CSF

and PET-PiB were collected in n = 71 and n = 91 participants, respectively, approximately four years prior to CAB testing.

For comparison, three traditional tests of delayed memory in parallel were examined. Similar to studies in older samples,

the CAB was less influenced by demographic factors than traditional tests. CAB tests were generally correlated with most

paper-based cognitive tests examined and mapped onto the same cognitive domains. Greater composite cognitive

impairment index was associated with worse performance on all CAB tests. Cognitively impaired participants performed

significantly worse compared to normal controls on all but one CAB test. Poorer One Card Learning test performance was

associated with higher levels of CSF phosphorylated tau/Aβ42. The authors concluded that these results support the use

of the CogState battery as measures of early cognitive impairment in studies of people at risk for AD. However, according

to the authors, the study also suggests that CogState at a single time point may not substantially improve preclinical AD

detection over traditional neuropsychological tests.

Shopin et al. (2013) compared a computerized battery of neuropsychological tests for memory, attention, and executive

functions (MindStreams) with the Montreal Cognitive Assessment (MoCA) to detect mild-to-moderate cognitive

impairments in poststroke patients. A total of 454 patients with transient ischemic attack (TIA) or stroke enrolled to the

TABASCO (Tel Aviv Brain Acute Stroke Cohort) study, a prospective study which includes consecutive first-ever mild-to-

moderate stroke patients, were included. All participants underwent neurological and cognitive evaluations. The patients’

mean MoCA and MindStreams scores were lower than normal; however, the TIA group presented significantly better

scores using either method. The correlation between the MoCA and the computerized global score was 0.6. A significant

correlation was found between the subcategory scores (executive function, memory, and attention). However, the MoCA

identified many more subjects with low scores (< 26) compared to the MindStreams (70.6 vs. 15.7%).

Intermittent Explosive Disorder

There is insufficient clinical evidence to demonstrate that the use of neuropsychological testing for individuals with

intermittent explosive disorder without associated cognitive disorders can be used effectively for clinical decision making

to improve patient management of this condition.

There are no clear underlying medical issues associated with intermittent explosive disorder, nor are there published

clinical trials that support the use of neuropsychological testing for this disorder. According to the Diagnostic and

Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association, the following criteria

must be met in order for a patient to be diagnosed with intermittent explosive disorder:

• Recurrent behavioral outbursts that represent a failure to control aggressive impulses as manifested by one of the

following:

o Verbal aggression (e.g., temper tantrums, tirades, verbal arguments, or fights) or physical aggression towards

property, animals, or other individuals, occurring, on average, twice weekly for a period of three months. The

physical aggression does not result in damage or destruction of property and does not result in physical injury to

animals or other individuals.

o Three behavioral outbursts involving damage or destruction of property and/or physical assault with physical

injury against animals or other individuals occurring within a 12-month period.

• The magnitude of aggressiveness expressed during the recurrent outbursts is grossly out of proportion to the

provocation or any precipitating psychosocial stressors.

• The recurrent aggressive outbursts are not premeditated (i.e., are impulsive) and are not committed to achieve some

tangible objective (e.g., money, power, intimidation).

• The recurrent aggressive outbursts cause either marked distress in the individual or impairment in occupational or

interpersonal functioning or are associated with financial or legal consequences.

• Chronological age is at least 6 years (or equivalent developmental level).

• The recurrent aggressive outbursts are not better explained by another mental disorder and are not attributable to

another medical condition or to physiological effects of a substance.

Headaches Including Migraine

There is insufficient clinical evidence to demonstrate that the use of neuropsychological testing for individuals with

migraine or other headaches without associated cognitive disorders can be used effectively for clinical decision making to

improve patient management of this condition.

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In their omnibus meta-analysis that evaluated performance on clinical measures of neuropsychological function in people

with migraine (PwM) and healthy controls (HC), Pizer et al. (2024) included 58 studies with 5,452 PwM (mean age 66

years, 60% male) and 16,647 HCs (mean age 69 years, 55% male). Types of migraines reported were unspecified (n =

2,381), chronic (n = 234), episodic (n = 19), with aura (n = 846) and without aura (2,046). Neuropsychological test scores

were obtained from 144 different neuropsychological outcome measures across the 10 content domains. Study quality

was considered good for 14 (24%) of the 58 included studies, fair for 38 (66%), and poor for 6 (10%). The authors

reported that there was a lower overall cognitive performance in PwM than in HCs, although there was high between-

study heterogeneity. The authors found significant domain-specific negative effects in global cognition, executive function,

processing speed, visuospatial/construction, simple/complex attention, learning memory, and language while orientation,

motor, and intelligence were not significant. Moderator analyses by the authors showed that age (particularly younger

HCs), samples drawn from health care facilities versus community-based populations, and higher attack duration were

associated with larger (negative) effects and accounted for a significant proportion of between-study heterogeneity in

effects. The authors stated that PwM without aura yielded stronger (negative) effects when compared to those PwM with

aura, although the aura status did not account for heterogeneity between the studies. The authors concluded that PwM

demonstrated worse neurocognition than HCs based on neuropsychological tests, especially on cognitive screening tests

and tests within executive functioning and processing speed domains, while the effects were generally small to moderate

in magnitude and evident only in clinic samples, and that an aura was not meaningfully associated with neurocognitive

impairment. Limitations of the study include the heterogeneity of the study populations, types of migraines and

neuropsychological tests used, the lack of reporting of medication utilization for moderator analysis, the inability to confirm

that potential cognitive deficits were attributable to the neural substrates of migraine, the potential for mis categorization of

cognitive outcomes, and the lack of potential for experimenter bias due to lack of preregistration of the protocol for this

study.

Lozano-Soto et al. (2023) conducted a case-control study to examine the presence of neuropsychological deficits in

chronic migraine (CM) patients during the interictal phase. The study included 39 CM patients recruited from a single

outpatient center and 20 age-, sex-, and education-matched healthy controls (HCs). All study participants underwent

clinical, neuropsychiatric, and neuropsychological evaluation by a clinical neurologist to evaluate cognitive domains,

including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory

(WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than

HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. The

authors reported that more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI)

with 35.9% classified as having mild NI, 12.8% with moderate NI and 5.1% with severe NI. Additional exploratory analysis

showed that more than half (54%) of CM patients with mild, moderate, or severe NI took two or more than two

medications and that the severity of NI was associated with the number of treatments received. The authors reported that

CM patients exhibited variable NI during periods between acute migraine attacks and that the patients demonstrated

cognitive impairment in SA, verbal episodic memory, and Stroop-like interference. Limitations of the study included the

small sample size, the single center design, and the large variety of the treatments that the patients received. The authors

concluded that CM can be accompanied by a variety of cognitive symptoms during the interictal phase and that these

cognitive impairments were most likely related to the mechanisms underlying migraine-induced disability.

In another study that investigated the cognitive impairment of migraineurs, Qin et al. (2022) enrolled 117 adult patients

with primary headaches, including 87 with migraine, 30 with tension-type headache (TTH) and 30 healthy controls. No

significant differences were found in age, sex, or years of education among the three groups. The authors reported that

the Montreal Cognitive Assessment (MoCA) total score and the scores of visuospatial and executive functions, language,

and delayed recall in the migraine and TTH groups were significantly lower than those in the healthy control group (all p <

0.05) while no significant differences were observed in naming, attention, abstraction, and orientation between the

patients and healthy controls. Limitations of the study included the questionnaire and scales to assess the study subjects,

the risk of recall bias in the evaluation of the subjects’ anamnestic description of migraine history, the small sample size,

the short-term follow-up period the lack of supplementary examinations and the lack of specific information regarding

antimigraine medication use and type. The authors concluded the study confirmed cognitive impairment in patients with

migraine and TTH and that the duration of attack had an effect on cognitive function in migraineurs.

A cross-sectional study by Chen et al. (2021) was performed to assess whether patients with migraine without aura

(MwoA) during the interictal period have attention impairment and to identify the migraine characteristics related to

attention deficits. Forty-four subjects with MwoA (4 males, 40 females) and 20 controls matched for age, gender, and

literacy education were included in the study. The attention network test (ANT) and a battery of neuropsychological tests,

including the trail-making test (TMT), the digit span test (DST), and the Stroop test, were administered to the participants

during the headache-free period. Patients in MwoA were more anxious (p = 0.007) and depressed (p = 0.001) than

healthy subjects. Significant differences between the two groups were detected in the executive network (p = 0.006) but

not in the alerting and orienting networks of ANT. Mean reaction time of ANT in the MwoA group was significantly longer

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than that in the control group (p = 0.028). Patients showed worse performance on DST-forward (p < 0.001), DST-

backward (p < 0.001), DS Total (p < 0.001), TMT-A (p < 0.001), TMT-B (p < 0.001) and TMT-d (p = 0.002). Differences

found in executive functions between the two groups were unrelated to gender, age, literacy, anxiety, and depression.

Multiple regression analysis revealed no relation between clinical characteristics of headache and scores on the executive

function with MwoA. The authors concluded that the study suggested that patients in MwoA present worse performances

on the executive control of attention networks during the headache-free period, which appear not be associated with

measures of migraine severity. The authors also stated although more studies are needed in this area, the results could

be useful to find a specific neuropsychological biomarker for migraine pathophysiology. A small sample size makes it

difficult to decide whether these conclusions can be generalized to a larger population. Further research with randomized

controlled trials is needed to validate these findings.

Foti et al. (2017) identified 16 studies evaluating the association between migraine and cognitive impairment. The authors

found that these studies demonstrated conflicting results. Some studies show a detrimental effect of migraine on cognitive

skills and other studies have shown no difference in cognitive skills for patients with migraine headaches.

Dresler et al. (2012) evaluated three neuropsychological tests (Trail Making Test (TMT), Go/Nogo Task and Stroop Task)

that were completed by four headache patient samples (chronic CH, episodic CH in the active or inactive period, and

migraine patients) and compared to healthy controls. Analyses revealed that patients with chronic and active episodic CH

appeared particularly impaired in tests relying more on intact executive functioning (EF) than on basal cognitive

processes. Within the CH groups performance decreased linearly with increasing severity. The authors stated that

impaired EF could also result from medication and sleep disturbances due to active CH. The authors went on to say that

because decreased performance was also present outside the attacks it may hint at generally altered brain function but

does not necessarily reflect clinically relevant behavior.

History of Myocardial Infarction

There is insufficient clinical evidence to demonstrate that the use of neuropsychological testing for individuals with a

history of myocardial infarction without associated cognitive disorders can be used effectively for clinical decision making

to improve patient management of this condition.

Studies on the relationship between myocardial infarction and cognitive functioning have demonstrated conflicting results.

Some studies show a detrimental effect of myocardial infarction on cognitive skills (Gallagher et al., 2023; Sauvé et al.,

2009; Almeida et al., 2008). Other studies have shown no difference in cognitive skills for patients with myocardial

infarctions (Ahto et al., 1999, Grubb et al., 2000).In a systematic review, Cameron et al. (2016) evaluated the diagnostic

accuracy of cognitive screening instruments in screening for mild cognitive impairment (MCI) in heart failure (HF) patients.

Inclusion criteria for the review were as follows: primary studies examining cognitive impairment in HF, administration of a

cognitive screening instrument and neuropsychological test battery, and cognitive impairment indicated by performance

on neuropsychological tests 1.5 SDs less than that of normative data. The precision, accuracy, and receiver operating

characteristic curves of the Mini Mental State Examination were computed. From 593 citations identified, 8 publications

met inclusion criteria. Risk of bias included selective HF patient samples, and no study examined the diagnostic test

accuracy of the cognitive screening instruments. The Mini Mental State Examination had low sensitivity (26%) and high

specificity (95%) with a score of 28 or less as the optimal threshold for MCI screening. The authors concluded that

screening for cognitive impairment in HF is recommended; however, future studies need to establish the diagnostic

accuracy of screening instruments of MCI in this population.

Self-Administered or Self-Scored Neuropsychological Testing

The evidence is insufficient to establish the validity and reliability of self-administered or self-scored neuropsychological

testing, whether paper-and-pencil or computerized, as a screening tool of cognitive function or for diagnosing neurological

disease. Prospective controlled trials are needed to demonstrate the clinical utility of these tests to detect impairment in

neuropsychological processing.

Sloane et al. (2023) conducted a single-center, prospective cohort study to evaluate the feasibility and effectiveness of the

Miro tablet-based, self-administered neurocognitive mobile application with cognitive games that are intended to detect

and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. This study included 79

patients (mean age 62.9 years old, 61% male, 70% had at least college education) who were randomized to either

undergo pencil-and-paper or tablet testing. Participants were evaluated and diagnosed with cognitive impairment based

on clinical assessment, neuroimaging evaluation and neuropsychological testing prior to study enrollment. The cohort

included cognitively impaired adults with right and left hemispheric strokes, mild cognitive impairment, various

neurodegenerative disorders such as Alzheimer’s dementia, Parkinsonism related cognitive impairment, or Primary

Progressive Aphasia (PPA). The study also included 29 age-matched healthy controls with the same inclusion and

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exclusion criteria as patients but without a neurological diagnosis. All participants completed both pencil-and-paper and

tablet assessments. The authors reported that there were statistically significant Pearson correlations between the

neuropsychological tests and the tablet equivalents in all domains with moderate or strong correlations in 16 of 17 tests.

The authors also reported that all tablet-based subtests differentiated healthy controls from neurologically impaired

patients except for the Spatial Span Forward and Finger Tapping modules. Limitations of the study include the single

center design, the small sample size, the heterogeneity of diagnostic groups included, and the cross-sectional view of

participant performance. The authors concluded that the Miro mobile application was found to be widely acceptable to

participants and that it supported the validity of the assessments in the differentiation of healthy controls from patients with

neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Oliva et al. (2022) performed a validation study of the NAIHA Neuro Cognitive Test (NNCT), a computerized, self-

administered neuropsychological screening test designed for elderly people with and without cognitive impairment via

digitized cognitive assessments. The study included 147 adults over 65 years of age. The authors reported that the

validity of the NNCT was demonstrated by correlating outcomes from the Mini Mental State Exam (MMSE), the Clock

Drawing Test (CDT) and the Cambridge Cognitive Examination-Revised (CAMCOG-R) test as all subscales of the NNCT

test correlated significantly and positively with some of these tests. The authors reported that the NNCT also discriminated

correctly to assign the participants into the three groups, Healthy Older Adults (HOA; n = 70), mild cognitive impairment

(MCI; n = 44) and Alzheimer’s dementia (AD; n = 33) and that the test can be used for screening and for diagnostic

support. Limitations of the study include the small sample size, the single center design, and the inability of some

participants to complete all phases of the study due to poor vision and limited ability to use tablet devices.

A cross-sectional study by Paterson et al. (2022) was performed to validate the online Brain Health Assessment (BHA) for

detection of amnestic mild cognitive impairment (aMCI) compared to gold-standard neuropsychological assessment, the

Montreal Cognitive Assessment (MoCA). Using a cross-sectional design, community-dwelling older adults completed a

neuropsychological assessment, were diagnosed as normal cognition (NC) or aMCI and completed the BHA and MoCA.

Both logistic regression (LR) and penalized logistic regression (PLR) analyses determined BHA and demographic

variables predicting aMCI; MoCA variables were similarly modeled. Diagnostic accuracy was compared using area under

the receiver operating characteristic curve (ROC AUC) analyses. Ninety-one participants met inclusion criteria (51 aMCI,

40 NC). PLR modeling for the BHA indicated Face– Name Association, Spatial Working Memory, and age-predicted aMCI

(ROC AUC = 0.76; 95% confidence interval [CI]: 0.66–0.86). Optimal cut-points resulted in 21% classified as aMCI

(positive), 23% negative, and 56% inconclusive. For the MoCA, digits, abstraction, delayed recall, orientation, and age

predicted aMCI (ROC AUC = 0.71; 95% CI: 0.61–0.82). Optimal cut-points resulted in 22% classified positive, 8%

negative, and 70% inconclusive (LR results presented within). The BHA model classified fewer participants into the

inconclusive category and more as negative for aMCI, compared to the MoCA model (Stuart–Maxwell p = .004). The

authors concluded that self-administered BHA provides similar detection of aMCI as a clinician-administered screener

(MoCA), with fewer participants classified inconclusively. The BHA has the potential to save practitioners time and

decrease unnecessary referrals for a comprehensive assessment to determine the presence of aMCI. Further research

with randomized controlled trials (RCTs) is needed to validate these findings.

A cross-sectional study by Vyshedskiy et al. (2022) was performed to assess test scores and the correlation between

Boston Cognitive Assessment (BOCA) and Montreal Cognitive Assessment (MoCA) test scores. BOCA is a self-

administered 10-minute at-home test intended for longitudinal cognitive monitoring, and MoCA, a gold standard pen-and-

paper test of global cognition. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA

evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Combinatorial Language Comprehension/Prefrontal

Synthesis, 3) Visuospatial Reasoning/Mental rotation, 4) Executive function/Clock Test, 5) Attention, 6) Mental math, 7)

Orientation, and 8) Memory/Delayed Recall. A total of 100 patients were included in the study. BOCA was administered to

patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were

significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach’s

alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with MoCA (r = 0.90, p <

.0.001). The study revealed strong (r = 0.94, p < 0.001) test-retest reliability of the total BOCA score one week after

participants’ initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant

(β = 0.03, p = 0.68). The effect of the screen size tested by BOCA administration on a large computer screen and re-

administration of the BOCA to the same participant on a smartphone was insignificant (β = 0.82, p = 0.17; positive β

indicates greater score on a smartphone). The authors concluded that BOCA has the potential to reduce the cost and

improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse

cognitive aging. The authors also state that additionally, the test can be used to assess the effect of anesthesia, long-term

effect of cancer drugs, COVID fog, and other conditions know to affect cognition. Further research with randomized

controlled trials is needed to validate these findings.

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A randomized clinical trial was completed by Mahncke et al. (2021) to evaluate the efficacy of self-administered

computerized cognitive training. A multisite randomized double-blind clinical trial of a behavioral intervention with an active

control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after

a 3-month follow-up period. The goal of this study was to evaluate the efficacy of a self-administered computerized

plasticity-based cognitive training programs in primarily military/veteran participants with a history of mTBI and cognitive

impairment. Participants self-administered cognitive training (experimental and active control) programs at home, remotely

supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 hour per day, for 13 weeks.

Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury)

through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or

quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized

cognitive training program targeting speed/accuracy of information processing, and the active control was composed of

computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological

assessments, and the primary directly observed functional measure a timed instrumental activities of daily living

assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health.

The treatment group showed an improvement in the composite cognitive measure larger than that of the active control

group at both the post-training [+ 6.9 points, confidence interval (CI) + 1.0 to + 12.7, p = 0.025, d = 0.555] and the follow-

up visit (+ 7.4 points, CI + 0.6 to + 14.3, p = 0.039, d = 0.591). Both large and small cognitive function improvements were

seen twice as frequently in the treatment group than in the active control group. No between-group effects were seen on

other measures, including the directly observed functional and symptom measures. Statistically equivalent improvements

in both groups were seen in depressive and cognitive symptoms. Further investigation is needed before clinical

usefulness of this procedure is proven.

A cohort study by Scharre et al. (2021) was performed to compare longitudinal Self-Administered Gerocognitive

Examination (SAGE) test scores to non-self-administered Mini-Mental State Examination (MMSE) scores in 5 different

diagnostic subgroups. A cohort study evaluating annual rates of change was performed on 665 consecutive patients from

Ohio State University Memory Disorders Clinic. Patients with at least two visits 6 months apart evaluated with SAGE and

MMSE and classified according to standard clinical criteria as subjective cognitive decline (SCD), mild cognitive

impairment (MCI), or AD (AD) dementia were included. The pattern of change in SAGE scores was compared to MMSE.

One way and repeated measures ANOVA and linear regression models were used. Four hundred twenty-four individuals

(40 SCD, 94 MCI non-converters to dementia, 70 MCI converters to dementia (49 to AD dementia and 21 to non-AD

dementia), 220 AD dementia) met inclusion criteria. SAGE and MMSE scores declined respectively at annual rates of

1.91 points/year (p < 0.0001) and 1.68 points/year (p < 0.0001) for MCI converters to AD dementia, and 1.82 points/year

(p < 0.0001) and 2.38 points/year (p < 0.0001) for AD dementia subjects. SAGE and MMSE scores remained stable for

SCD and MCI non-converters. Statistical decline from baseline scores in SAGE occurred at least 6 months earlier than

MMSE for MCI converters to AD dementia (14.4 vs. 20.4 months), MCI converters to non-AD dementia (14.4 vs. 32.9

months), and AD dementia individuals (8.3 vs. 14.4 months). The authors concluded that SAGE detects MCI conversion

to dementia at least 6 months sooner than MMSE. Being self-administered, SAGE also addresses a critical need of

removing some barriers in performing cognitive assessments. Limitations of this study include potential referral and

sampling biases. Repetitively administering SAGE and identifying stability or decline may provide clinicians with an

objective cognitive biomarker impacting evaluation and management choices. Further research with randomized

controlled trials is needed to validate these findings.

Clinical Practice Guidelines

American Academy of Child and Adolescent Psychiatry (AACAP)

Practice parameters from the AACAP (Volkmar et al., 2014) state that neuropsychological correlates of autism spectrum

disorder include impairments in executive functioning (e.g., simultaneously engaging in multiple tasks) (Ozonoff et al.,

1991), weak central coherence (integrating information into meaningful wholes) (Happe and Frith, 2006), and deficits in

theory-of-mind tasks (taking the perspective of another person) (Baron-Cohen et al., 1985).

In their 2007 Practice Parameter on the assessment and treatment of children and adolescents with ADHD, Pliszka et al.

(2007) reported that patients with ADHD have impairments in the executive functioning domains of response inhibition,

vigilance, working memory, and some measures of planning, although not all patients with ADHD show executive function

deficits. Their recommendation states that psychological and neuropsychological tests are not mandatory for the

diagnosis of ADHD but should be performed if the patient’s history suggests low general cognitive ability or low

achievement in language or mathematics relative to the patient’s intellectual ability.

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American Academy of Clinical Neuropsychology (AACN) and National Academy of

Neuropsychology (NAN)

A joint position paper of the AACN and NAN sets forth their position on appropriate standards and conventions for

computerized neuropsychological assessment devices (CNADs). The authors state that CNADs are subject to, and

should meet, the same standards for the development and use of educational, psychological, and neuropsychological

tests (American Psychological Association, 1999) as are applied to examiner-administered tests. The authors also state

that those employing CNADs have the education, training, and experience necessary to interpret their results in a manner

that will best meet the needs of the patients they serve (Bauer et al., 2012).

American Academy of Neurology (AAN)

In an evidence-based guideline update for the evaluation and management of concussion in sports, the AAN states that it

is likely that neuropsychological testing of memory performance, reaction time, and speed of cognitive processing,

regardless of whether administered by paper-and-pencil or computerized method, is useful in identifying the presence of

concussion (sensitivity 71%–88% of athletes with concussion). This is based on evidence from 1 Class II study and

multiple Class III studies. The AAN also states that both types of testing (paper-and-pencil or computerized) generally

require a neuropsychologist for accurate interpretation, although the tests may be administered by a non-

neuropsychologist. According to AAN, there is insufficient evidence to support conclusions about the use of

neuropsychological testing in identifying concussion in preadolescent age groups. The AAN goes on to say that

inexperienced licensed health care providers (LHCPs) should be instructed in the proper administration of standardized

validated sideline assessment tools. This instruction should emphasize that these tools are only an adjunct to the

evaluation of the athlete with suspected concussion and cannot be used alone to diagnose concussion (Level B –

probably effective). The AAN further states that LHCPs caring for athletes might utilize individual baseline scores on

concussion assessment tools, especially in younger athletes, those with prior concussions, or those with preexisting

learning disabilities/attention deficit/hyperactivity disorder, as doing so fosters better interpretation of postinjury scores

(Level C – Possibly effective) (Giza et al., 2013, reaffirmed 2022).

A practice guideline update for disorders of consciousness (DoC) developed by the American Academy of Neurology; the

American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and

Rehabilitation Research indicates that clinicians should use standardized neurobehavioral assessment measures that

have been shown to be valid and reliable to improve diagnostic accuracy for the purpose intended in patients with DoC

(Giacino et al. 2018, reaffirmed 2021).

In a practice guideline update summary for mild cognitive impairment (MCI), the AAN recommends that when performing

a Medicare Annual Wellness Visit, clinicians should not rely on historical report of subjective memory concerns alone

when assessing for cognitive impairment (Level B). Various assessment instruments have acceptable diagnostic accuracy

for detecting MCI, with no instrument being superior to another. The guideline states that because brief cognitive

assessment instruments are usually calibrated to maximize sensitivity rather than specificity, patients who test positive for

MCI should then have further assessment (e.g., more in-depth cognitive testing, such as neuropsychological testing with

interpretation based on appropriate normative data) to formally assess for this diagnosis (Petersen et al., 2018; reaffirmed

2021).

American Academy of Pediatrics (AAP)

A joint statement for learning disabilities, dyslexia, and vision from the AAP, Section on Ophthalmology, Council on

Children with Disabilities; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and

Strabismus; and the American Association of Certified Orthoptists states that children who exhibit signs of learning

disabilities should be referred for educational, psychological, neuropsychological, and/or medical diagnostic assessments

(AAP, 2009; Reaffirmed 2014).

In 2018, the AAP updated the clinical report guidance for sport-related concussion (SRC) in children and adolescents. The

authors of the report indicate that there are numerous studies evaluating the reliability of various computerized

neurocognitive tests (CNTs) platforms; however, studies conducted independently of the developers of the tests have

questioned the overall reliability of testing from year to year. The reliability of pencil and paper testing has also been

questioned. The authors indicate that ideally, neurocognitive testing is performed and interpreted by a neuropsychologist.

However, given the large number of athletes participating in sports and the relative scarcity of and limited access to

neuropsychologists, a widespread CNT program would not be practical or possible. If a non-neuropsychologist is using

CNTs, collaboration with a neuropsychologist to aid in test administration and interpretation may be beneficial. CNTs or

baseline testing is not specifically addressed in the conclusion or recommendation sections of the report (Halstead et al.,

2018).

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American Heart Association (AHA) and American Stroke Association

In a guideline for Healthcare Professionals from the AHA and the American Stroke Association, Winstein et al. (2016)

provided a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. According to the

guideline, a formal neuropsychological examination (including assessment of language, neglect, praxis, memory,

emotional responses, and specific cognitive syndromes) may be helpful after the detection of cognitive impairment with a

screening instrument. Neuropsychological protocols must be sensitive to a wide range of abilities, especially the

assessment of executive and attentional functions. These guidelines state that screening for cognitive deficits is

recommended for all stroke patients before discharge home (class I, level B evidence). The guidelines also indicate that

when screening reveals cognitive deficits, a more detailed neuropsychological evaluation to identify areas of cognitive

strength and weakness may be beneficial (class Iia, level C evidence).

American Medical Society for Sports Medicine (AMSSM)

The AMSSM position statement on concussion in sport states that baseline testing may be useful in some cases but is not

necessary, required or an accepted standard of care for the appropriate management of sport-related concussion

(Harmon et al., 2019).

American Psychological Association (APA)

The APA published a Psychological and Neuropsychological Testing Billing and Coding Guide (American Psychological

Association, 2019). The guide states that neuropsychological testing is considered medically necessary where initial

assessment or assessment over time is needed to:

• Measure cognitive or behavioral deficits related to known or suspected CNS impairment, trauma, or neuropsychiatric

disorders, including when the information will be useful in determining a diagnosis, prognosis, or informing treatment

planning;

• Evaluate primary symptoms of impaired attention and concentration that can occur in many neurological and

psychiatric conditions;

• Determine the potential impact of substances that may cause cognitive impairment (e.g., radiation, chemotherapy,

prescribed or illicit drugs, toxins) or result in measurable improvement in cognitive function, including when this

information is used to determine treatment planning;

• Conduct pre-surgical or treatment-related measurement of cognitive function to determine whether it is safe to

proceed with a medical or surgical procedure that may impact brain function (e.g., deep brain stimulation, resection of

brain tumors or arteriovenous malformations, epilepsy surgery, stem cell or organ transplant) or significantly alter a

patient’s functional status;

• Design, administer, and/or monitor outcomes of cognitive rehabilitation procedures, such as compensatory memory

training for brain-injured patients;

• Measure cognitive or functional deficits in children and adolescents based on an inability to develop expected

knowledge, skills or abilities as required to adapt to cognitive, social, emotional, or physical demands;

• Evaluate primary symptoms of impaired attention and concentration that can occur in many neurological and

psychiatric conditions

The American Psychological Association Guide (2019) also indicates that neuropsychological testing is not considered

reasonable and necessary when:

• Administered for educational or vocational purposes that do not inform medical or health management

• Comprised exclusively of self-administered or self-scored inventories, or as screening tests of cognitive function or

neurological disease (whether paper-and-pencil or computerized, e.g., AIMS, Folstein Mini-Mental Status

Examination)

• The patient is neurologically, cognitively, or psychologically unable to participate in a meaningful way in the testing

process

• Used as a routine screening tool given to the individual or to general populations

• Repeat testing is not required for medical decision-making

• Administered when the patient is currently under the influence or impaired by alcohol, drugs (prescription or illicit), or

other substances

• The patient has been diagnosed previously with brain dysfunction, such as AD, and there is no expectation that the

testing would impact the patient’s medical, functional, or behavioral management

The APA published updated guidelines for the evaluation of dementia and age-related cognitive change. The guidelines

include the following information regarding neuropsychological testing for this condition (American Psychological

Association, 2012; updated 2021):

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• Neuropsychological evaluation and cognitive testing remain among the most effective differential diagnostic methods

in discriminating pathophysiological dementia from age-related cognitive decline, cognitive difficulties that are

depression-related, and other related disorders. Even after reliable biological markers have been discovered,

neuropsychological evaluation and cognitive testing will still be necessary to determine the onset of dementia, the

functional expression of the disease process, the rate of decline, the functional capacities of the individual, and

hopefully, response to therapies.

• Comprehensive neuropsychological evaluations for dementia and cognitive change include tests of multiple cognitive

domains, typically including memory, attention, perceptual and motor skills, language, visuospatial abilities, reasoning,

and executive functions. Measures of mood and personality may be relevant in many cases. Psychologists are

encouraged to refer to current compendia resources and the clinical research literature in selecting assessment

instruments. Psychologists are aware that standardized psychological and neuropsychological tests are important

tools in the assessment of dementia and age-related cognitive change.

• Technology assisted assessments (e.g., computer administered cognitive batteries, tele-health visits) are rapidly

advancing but appropriate psychometric properties and normative data are nascent. These technologies may have

significant advantages for older persons with limited mobility or health-care access but may also disadvantage older

persons with limited experience and expertise interacting with technology.

National Academy of Neuropsychology (NAN)

The NAN developed an education paper to provide information to clinicians, healthcare administrators, and policy

developers about the purpose, strengths, and limitations of computerized cognitive screening tests versus comprehensive

neuropsychological evaluations. Screening tests are generally brief and narrow in scope, they can be administered during

a routine clinical visit, and they can be helpful for identifying individuals in need of more comprehensive assessment.

Some screening tests can also be helpful for monitoring treatment outcomes. Comprehensive neuropsychological

assessments are multidimensional in nature and used for purposes such as identifying primary and secondary diagnoses,

determining the nature and severity of a person’s cognitive difficulties, determining functional limitations, and planning

treatment and rehabilitation. Cognitive screening tests are expected to play an increasingly important role in identifying

individuals with cognitive impairment and in determining which individuals should be referred for further

neuropsychological assessment. However, limitations of existing cognitive screening tests are present and cognitive

screening tests should not be used as a replacement for comprehensive neuropsychological testing (Roebuck-Spencer et

al, 2017).

In a policy for the evaluation of childhood learning disorders, the NAN states that when comprehensive information about

a child’s brain-related strengths and weaknesses is necessary to understand potential sources of the problem and

implications for functioning, a neuropsychological evaluation is most often the best choice (Silver et al., 2006).

In a position paper on the diagnosis and management of sports-related concussion, the NAN states that

neuropsychological evaluation is recommended for the diagnosis, treatment, and management of sports-related

concussion at all levels of play (Moser et al., 2007).

National Institute for Health and Care Excellence (NICE)

In their guideline for the management of Multiple Sclerosis, NICE (2022) advises that the practitioner should be aware that

the symptoms of MS can include cognitive problems, including memory problems. The guideline recommends that

cognition should be assessed as part of the person’s comprehensive review and that the assessment should be tailored to

the person’s needs, which may include a clinic interview or brief formal assessment, or consideration of a referral for a full

neuropsychological assessment if needed.

Dementia assessment, management and support guidelines published by NICE (2018) state that following initial

assessment and diagnosis of suspected dementia, patients are to be referred to a specialist once reversible causes of

cognitive decline have been ruled out. Following standard, validated criteria use and assessment, neuropsychological

testing may be considered if it is unclear:

• Whether the patient has cognitive impairment; or

• Whether their cognitive impairment is caused by dementia; or

• What the correct subtype diagnosis is

US Preventive Services Task Force (USPSTF)

A recommendation statement published by the USPSTF(2020) on screening for cognitive impairment in older adults,

including neuropsychological testing, concludes that the current evidence is insufficient to assess the balance of benefits

and harms of screening for cognitive impairment.

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U.S. Food and Drug Administration (FDA)

This section is to be used for informational purposes only. FDA approval alone is not a basis for coverage.

In March 2021, the FDA cleared the ANAM Test system for Computerized Cognitive Assessment Aid for concussion. The

ANAM system is an assessment aid in the management of concussion. The device consists of a software program that

administers a battery of neurocognitive tests to an individual to assess their cognitive status. The device may be used with

an off-the-shelf computer or a novel device. Refer to the following websites for more information:

• https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?id=3918

• https://www.accessdata.fda.gov/cdrh_docs/pdf20/K201376.pdf. (Accessed May 15, 2024)

In June 2015, the FDA cleared Cognivue through the de novo classification pathway. The de novo pathway is used for

low- to moderate-risk medical devices that are not equivalent to an already legally marketed device. FDA identifies

Cognivue as a “Computerized Cognitive Assessment Aid.” According to the FDA, this test is indicated as an adjunctive

tool for evaluating perceptual and memory function in individuals aged 55 to 95 years old. Refer to the following website

for more information: https://www.accessdata.fda.gov/cdrh_docs/pdf13/DEN130033.pdf

. (Accessed May 15, 2024)

On August 22, 2016, the FDA began to allow the marketing of two computerized neurocognitive tests for assessing

individuals immediately following a suspected brain injury or concussion: ImPACT and ImPACT Pediatric (ImPACT

Applications). Both tests were reviewed via the agency’s de novo classification process, a pathway to market for certain

“first-of-a-kind” and low- to-moderate-risk medical devices. ImPACT and ImPACT Pediatric are computerized cognitive

assessment aids intended for use in conjunction with standard medical evaluation for signs and symptoms of a head

injury. ImPACT is designed to assess people 12 to 59 years of age, while ImPACT Pediatric is designed for children aged

5 to 11 years. The FDA states that these tests should not be used to “rule out a concussion or determine whether an

injured player should return to a game.” Refer to the following websites for more information:

• http://www.accessdata.fda.gov/cdrh_docs/pdf15/DEN150037.pdf

• http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm517526.htm. (Accessed May 15, 2024)

References

Abeare C, Messa I, Whitfield C, et al. Performance validity in collegiate football athletes at baseline neurocognitive testing.

J Head Trauma Rehabil. 2018 Nov 28.

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Policy History/Revision Information

Date

Summary of Changes

09/01/2024

Supporting Information

• Updated Clinical Evidence and References sections to reflect the most current information

• Archived previous policy version 2023T0152AA

Instructions for Use

This Medical Policy provides assistance in interpreting UnitedHealthcare standard benefit plans. When deciding coverage,

the member specific benefit plan document must be referenced as the terms of the member specific benefit plan may

differ from the standard plan. In the event of a conflict, the member specific benefit plan document governs. Before using

this policy, please check the member specific benefit plan document and any applicable federal or state mandates.

UnitedHealthcare reserves the right to modify its Policies and Guidelines as necessary. This Medical Policy is provided for

informational purposes. It does not constitute medical advice.

Neuropsychological Testing Under the Medical Benefit

Page 33 of 33

UnitedHealthcare Commercial and Individual Exchange Medical Policy

Effective 09/01/2024

This Medical Policy may also be applied to Medicare Advantage plans in certain instances. In the absence of a Medicare

National Coverage Determination (NCD), Local Coverage Determination (LCD), or other Medicare coverage guidance,

CMS allows a Medicare Advantage Organization (MAO) to create its own coverage determinations, using objective

evidence-based rationale relying on authoritative evidence (Medicare IOM Pub. No. 100-16, Ch. 4, §90.5

UnitedHealthcare may also use tools developed by third parties, such as the InterQual

criteria, to assist us in

administering health benefits. UnitedHealthcare Medical Policies are intended to be used in connection with the

independent professional medical judgment of a qualified health care provider and do not constitute the practice of

medicine or medical advice.