Neuropsychological Evaluation in Clinical Practice: Overview and Approach

Transcription

1 neurology Board Review Manual Statement of Editorial Purpose The Hospital Physician Neurology Board Review Manual is a peer-reviewed study guide for residents and practicing physicians preparing for board examinations in neurology. Each manual reviews a topic essential to the current practice of neurology. PUBLISHING STAFF PRESIDENT, Group PUBLISHER Bruce M. White Senior EDITOR Robert Litchkofski assistant EDITOR Farrawh Charles executive vice president Barbara T. White executive director of operations Jean M. Gaul Neuropsychological Evaluation in Clinical Practice: Overview and Approach Editors: Alireza Atri, MD, PhD Instructor in Neurology, Harvard Medical School; Assistant in Neurology, Memory Disorders Unit, Massachusetts General Hospital, Boston, MA Tracey A. Milligan, MD Instructor in Neurology, Harvard Medical School; Associate Neurologist, Brigham and Women s and Faulkner Hospitals, Boston, MA Contributors: Lynn W. Shaughnessy, MA Student, Massachusetts School of Professional Psychology, West Roxbury, MA Maureen K. O Connor, PsyD, ABCN Instructor, Department of Neurology, Boston University School of Medicine, Boston, MA; Director of Neuropsychology, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA Janet C. Sherman, PhD Assistant Professor, Department of Neurology, Harvard Medical School; Clinical Director, Psychology Assessment Center, Massachusetts General Hospital, Boston, MA PRODUCTION Director Suzanne S. Banish PRODUCTION assistant Nadja V. Frist sales & marketing manager Deborah D. Chavis NOTE FROM THE PUBLISHER: This publication has been developed without involvement of or review by the American Board of Psychiatry and Neurology. Table of Contents Introduction Goals of Neuropsychological Evaluation Clinical Method Dimensions of Behavior and Domains of Functioning Evaluated Summary References Cover Illustration by Nadja V. Frist Copyright 2009, Turner White Communications, Inc., Strafford Avenue, Suite 220, Wayne, PA ,. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications. The preparation and distribution of this publication are supported by sponsorship control over the design and production of all published materials, including selection of topics and preparation of editorial content. The authors are solely responsible for substantive content. Statements expressed reflect the views of the authors and not necessarily the opinions or policies of Turner White Communications. Turner White Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inaccuracies. Information contained within this publication should not be used as a substitute for clinical judgment. Neurology Volume 13, Part 3

2 Neurology Board Review Manual Neuropsychological Evaluation in Clinical Practice: Overview and Approach Lynn W. Shaughnessy, MA, Maureen K. O Connor, PsyD, ABCN, and Janet C. Sherman, PhD Introduction Neuropsychology is a science dedicated to understanding the intricate relationship between human behavior and the brain. Neuropsychologists and neurologists often work hand in hand, as neuropsychology can be used to enhance, expand, or support neurologic diagnoses in both clinical and research contexts. This manual, the first of a 2-part review of neuropsychology, provides an overview of the practice of neuropsychology, focusing on the goals of a neuropsychological evaluation, its methods, the cognitive domains assessed, and the interpretation of test results in an adult population. The second manual will demonstrate the application of fundamental concepts of neuropsychology in clinical practice by presenting the evaluation, counseling, and treatment recommendations for cases covering a broad spectrum of disorders, including an example of a neuropsychological evaluation of a child. Goals of Neuropsychological Evaluation Historically, the goal of a neuropsychological evaluation has been localization of lesions in patients who experience changes in cognition and/or behavior. 1 In the 1960s, Alexander Luria provided an outline for the clinical application of neuropsychology, describing its fundamental task as the qualitative analysis and evaluation of symptoms for local diagnosis of brain damage. 2 The lesion method can be traced back to the mid 1800s and publication of early case reports documenting the effects of brain damage on behavior. A well-known early case is that of Phineas Gage, a railroad worker who developed marked changes in personality and behavior after sustaining a significant frontal lobe injury. More recently, this method has been applied in in-depth experimental studies of patients such as HM, who underwent bilateral removal of a portion of the medial temporal lobes for intractable epilepsy, resulting Hospital Physician Board Review Manual in a dense anterograde amnesia. 3 To accomplish this goal of associating behavioral or cognitive impairment with the location of a lesion, early formalized methods of neuropsychological assessment related patterns of test scores obtained on a set battery of tests to specific brain regions (eg, Halstead-Reitan Battery 4 ). Less emphasis has been placed on this goal since the advent of sophisticated neuroimaging techniques, including magnetic resonance imaging (MRI), functional MRI, positron emission tomography, computed tomography, and magnetoencephalography. 5 Instead, neuropsychologists use the results of neuroimaging in conjunction with findings from the neuropsychological evaluation to better understand the patient s cognitive profile and the underlying neurologic basis of the patient s behavior. 6 In current practice, there are 4 major goals of neuropsychology: 1. Assessment of a patient s cognitive status across a range of domains to determine cognitive strengths and weaknesses. In many cases, the underlying etiology for a change in cognitive functioning is known, such as a neurologic injury (eg, a cerebrovascular accident, traumatic brain injury [TBI]) or neurologic disease (eg, epilepsy or Parkinson s disease). Within this context, the neuropsychological evaluation can provide information regarding the extent and nature of the patient s cognitive deficits and identify areas of functioning that have been preserved. This information can be used to guide patient care and treatment planning. Cognitive domains that are typically assessed within a neuropsychological evaluation include intellectual functioning, attention, frontal/ executive functioning, memory, language, visual perception, sensorimotor functions, and emotional functioning. 2. Assistance in addressing questions pertaining to differential diagnosis. Patients may be referred for neuropsychological testing to investigate an underlying etiology for changes in cognitive functioning that have been noticed by the patient, a family member, or a physician. In these cases, the patient s performance across a range of measures and cognitive

3 domains (ie, areas of cognitive strength and weakness) can help discriminate among different neurologic conditions as well as between psychiatric and neurologic conditions that may be causing a change in behavior and/or cognition (eg, dementia versus depression; normal aging versus a neurodegenerative process). On the most basic level, information obtained from a neuropsychological evaluation can be used to determine whether the patient is functioning within normal limits. Additionally, the neuropsychologist can examine whether there has been a change in functioning relative to the patient s premorbid status. 3. Monitoring of a patient s cognitive status over time with the use of repeat neuropsychological evaluations. While results from an initial evaluation can detect subtle cognitive deficits, the significance of these deficits is often better understood when compared with later results. This information is critical in determining whether there has been progression of cognitive difficulties, as would be expected in a neurodegenerative process, or whether there has been improvement over time. The latter determination is particularly important in assessing the extent to which a patient has benefited from a medical or psychotherapeutic intervention. 4. Providing recommendations regarding possible treatments and/or interventions that can help patients and their families. Based on the extent of a patient s deficits, a neuropsychologist can determine whether he or she may benefit from various types of interventions, what types of interventions would be most useful, in what ways the patient might use areas of strength to compensate for areas of weakness, and what specific treatment programs may be selected. 7 Neuropsychological evaluations also provide recommendations based on prognostic information to help patients and their families make functionally relevant decisions; these recommendations may focus on a patient s ability to independently manage aspects of daily living (eg, ability to manage finances, manage medications, maintain hygiene), return to work, comprehend and follow medical instructions, and comprehend legal documents. Clinical Method The request for a neuropsychological evaluation is typically made by a patient s primary care physician, treating neurologist, and/or treating psychiatrist or psychologist. Patients are often referred when they present to their physician with cognitive complaints, or when the physician detects difficulties in the office or on a brief mental status examination, such as the Mini Mental State Examination (MMSE). 8 The goals of the evaluation are guided by the information provided by the patient and the patient s family, the referral source, and the referral question itself (eg, Does this patient have depression or dementia?). Prior to conducting the evaluation, the neuropsychologist reviews all relevant available medical information, including the previous medical history and results of any diagnostic testing that has been conducted (eg, electroencephalogram, neuroimaging, blood laboratory tests). During the evaluation, the neuropsychologist conducts an in-depth interview to learn about the onset (insidious? abrupt?), course (Have the difficulties gotten better or worse over time or stayed the same?), and precise nature of the patient s cognitive difficulties; whether there have also been changes in mood and/or behavior; and how these difficulties impact functional ability. The neuropsychologist typically requests the presence of a collateral informant, often the patient s spouse or a family member, friend, or other individual who knows the patient well. The collateral informant is an integral part of the neuropsychological interview since many patients are unable to provide a detailed history and description of difficulties. During the interview, the neuropsychologist also obtains information about how a patient was functioning prior to the onset of difficulties. This information includes the patient s educational and occupational history and any previous history of psychiatric disorder, learning disability, attention deficit/hyperactivity disorder (ADHD), or previous neurologic difficulties that could impact performance on the neuropsychological measures. The major methodology used to investigate a patient s cognitive functioning within a neuropsychological evaluation is the administration of standardized tests for which there are normative data, or data about how a normal, nonimpaired similar individual would be expected to perform. To compare a patient s performance with normative data, neuropsychological tests must be administered and scored in a standardized manner, that is, in the same way as they were administered and scored for the normative sample. Given that the neuropsychological examination focuses on determining whether a patient is functioning normally relative to peers, neuropsychological measures compare patient functioning with available normative data for individuals who are the patient s same age and with some normative data stratified by gender and educational level. Test results are most valid when the patient closely matches the demographics of Neurology Volume 13, Part 3

4 Population under portions of normal curve, % Standard deviations 4σ 3σ 2σ 1σ 0σ +1σ +2σ +3σ +4σ Z-scores Standard scores/iq T-scores Scaled scores Percentiles Figure 1. A normative curve exhibiting the distribution of scores around the mean. The figure shows the relationships between different normative scores, with each having a different mean and standard deviation. (Reprinted from Sherman JC, Leveroni C, Pollak LN. Neuropsychological assessment. In: Stern TA, Rosenbaum JF, Fava M, et al, editors. Massachusetts General Hospital comprehensive clinical psychology. Philadelphia (PA): Mosby, Inc.; 2008:104. Copyright 2008, with permission from Elsevier.) the normative sample. Differences between the patient s demographics and those of the normative sample (eg, cultural or linguistic differences) are taken into account when the neuropsychologist interprets the test findings. Reliance on normative data is essential to understanding a patient s cognitive functioning, as not all individuals possess the same level of cognitive ability (Figure 1). Instead, there is a normal distribution of abilities for many cognitive functions. Neuropsychological test scores are expressed as standard scores in which the test score is described relative to the normative mean. For example, a standard score of 100 falls in the middle of the normative distribution (50th percentile), with half of the normative population achieving higher scores and half lower scores. A standard score of 85 falls 1 standard deviation below the mean, or at the 16th percentile (with only 16% of the population achieving lower scores). Scores that fall 2 or more standard deviations below the mean are considered to fall in the impaired range (Figure 2). The patient s test performance is also compared with an estimate of their premorbid level of functioning, which allows the neuropsychologist to address the question of whether there has been a change in his or her cognitive status (eg, as the result of a neurologic insult). Only by comparing a patient s test performance to a normative sample and to an estimate of premorbid functioning can the neuropsychologist address whether cognitive impairment is present, and if present, whether the impairment is likely the result of an underlying neurologic dysfunction. In addition to using precise quantitative data, the neuropsychologist also relies on examination of qualitative data in understanding a patient s cognitive impairments. Examples of qualitative information gathered during a neuropsychological evaluation include observations of the patient s interactions with the neuropsychologist, the level and consistency of effort the patient exerts during the evaluation, and the manner in which the patient approaches and carries out each task (eg, Is the approach organized or haphazard? Does the patient spontaneously self-correct errors or correct errors only when they are pointed out?). Also, although the tests themselves are administered in a standardized fashion, the instruments selected often vary from patient to patient (ie, a flexible rather than a fixed battery approach 9 ), with the neuropsychologist basing the selection of tests on the referral question, history, and performance on tests during the evaluation. Data collected from the record review, interview, patient observations, and cognitive testing are examined together to provide a detailed summary of the patient s cognitive profile, etiologic considerations, differential diagnosis, and recommendations. This summary is then provided to the referring physician in a detailed report and is also often reviewed by the neuropsychologist with the patient and his/her family in a subsequent feedback session. In the feedback session, the neuropsychologist helps the patient and his/her family understand the nature of any cognitive impairments, the implication that impairments have for possible diagnosis, the impact Hospital Physician Board Review Manual

5 Very Superior Superior High Average Average Low Average Borderline Impaired IQ SS %tile IQ SS %tile IQ SS %tile IQ SS %tile IQ SS %tile IQ SS %tile IQ SS %tile IQ SS %tile > > > > > > < < < < < < Figure 2. Standard score (SS) conversion to percentile, IQ score, and normalized classification. that impairments might have on patient functioning, and, importantly, how the patient can best address any areas of deficit. The neuropsychologist often provides recommendations about further evaluations that may be necessary, including neurologic evaluation, psychiatric consultation, psychotherapy, cognitive rehabilitation, and/or vocational guidance. Dimensions of Behavior and Domains of Functioning Evaluated A comprehensive neuropsychological evaluation typically examines several domains of cognitive functioning, with emphasis on domains that are most relevant to addressing the referral question and the patient s presenting symptoms. In the following sections, we briefly describe the domains that are typically assessed within a neuropsychological evaluation. Intellectual Functioning Intelligence can be thought of as an umbrella term that encompasses several different abilities, many of which are difficult to assess in a clinical setting. However, a neuropsychologist may attempt to obtain the best possible estimate of intelligence by integrating test results, demographic information, and historical information. Psychologist David Wechsler, author of the initial Wechsler Intelligence Scales (1939), 10 defined intelligence as the aggregate or global capacity of the individual to act purposefully, to think rationally, and to deal effectively with their environment. 11 Based upon this broad definition, Wechsler developed some of the most widely used intelligence tests for adults (the Wechsler Adult Intelligence Scale [WAIS] 12 ) and children (the Wechsler Intelligence Scale for Children [WISC] 13 ). These scales are composed of a variety of subtests measuring a number of multiply determined functions rather than a single ability, with performance on subtests combined to provide an intelligence quotient, or IQ. Although a patient s IQ score can be reduced secondary to neurologic insult (eg, TBI, stroke, neurodegenerative disease) relative to premorbid estimates, neuropsychologists are more interested in examining the various subtests independently to address more specific questions about functioning in particular domains of interest than they are in determining the patient s global IQ score. For example, the subtests on the fourth edition of the WAIS 12 assess a patient s functioning within 4 broad cognitive domains, including Verbal Comprehension, Perceptual Organization, Working Memory, and Processing Speed. The patient s performance within each of these domains provides insight into a patient s specific cognitive strengths or weaknesses and in turn helps guide the assessment process. As discussed, the neuropsychologist also estimates the patient s premorbid level of functioning when assessing intellectual functioning. Precise estimates of premorbid intelligence are important in preventing over- or underestimation of a patient s level of cognitive decline. 14 For example, an average range score on an executive functioning measure is interpreted differently for a patient with a premorbid IQ in the superior range as compared with a patient with a low average range Neurology Volume 13, Part 3

6 Table 1. Common Measures for the Assessment of Attention Component Assessed Attentional capacity/ attention span Working memory Selective attention Sustained attention/ vigilance Visual search and attention Processing speed premorbid IQ. These estimates typically rely on current performance on tests thought to be resistant to neurologic injury, demographic variables that generally correlate with intellectual functioning, or both. In general, a clinician chooses between or combines 4 standard methods of estimating premorbid intellectual functioning. The first employs actuarial formulas that utilize demographic information (eg, age, education, occupation, geographic region), such as the Barona Index. 15 A second method relies on performance on word reading tasks that tend to correlate highly with overall intellectual functioning (eg, North American Adult Reading Test, 16 Wechsler Test of Adult Reading 17 ). A third utilizes hold tests, which examine subtests from the WAIS that are considered relatively resistant to the effects of neurologic insult, 7 such as measures of vocabulary knowledge (WAIS-IV Vocabulary subtest 12 ) and measures of general fund of factual knowledge (WAIS-IV Information subtest 12 ). The fourth approach is the best performance method. In this method, the patient s highest level of functioning becomes the standard with which current performance is compared. 7 Although these 4 methods have somewhat limited sensitivity, studies indicate that informal estimates made by clinicians tend to be less accurate. 18,19 Attention Common Measures Used Digit Span Forward (WAIS-IV 12 ),Spatial Span Forward (WMS-III 26 ) Digit Span Backward (WAIS-IV), Digit Sequencing (WAIS-IV), Letter-Number Sequencing (WAIS-IV), Spatial Span Backward (WMS-III) Stroop Color and Word Test (Interference Condition), Brief Test of Attention 27 Conners Continuous Performance Test-II (CPT-II) 28 Trail Making Test Part A, 29 Letter and Symbol Cancellation Tasks, Visual Search and Attention Test (VSAT), 30 Line Bisection, Symbol Search (WAIS-IV) Digit Symbol (Coding) (WAIS-IV), Trail Making Test Part A, Trail Making Test Motor Speed, Condition 5 (D-KEFS 31 ), Stroop Color and Word Test 32 (Color and Word Reading) D-KEFS = Delis-Kaplan Executive Function System; WAIS = Wechsler Adult Intelligence Scale; WMS = Wechsler Memory Scale. Attention is a term that encompasses many different processes and can be broken down into subsystems that perform distinct but related functions, including the ability to orient to a stimulus, detect stimuli for focal or conscious processing, and maintain an alert or vigilant state. 20 Although clinical and research models use different terms for these processes, for the purpose of neuropsychological evaluation attention is commonly divided into component processes of arousal, attention span and working memory, selective attention, and sustained attention/vigilance. 18 Neuropsychologists also are often interested in evaluating aspects of spatial attention. Because the domain of attention is complex in nature and ultimately underlies many other cognitive domains, most tests of attention are multifactorial and often tap other domains. Specifically, many tests of attention are a combination of attention and executive functioning measures with lesser or greater need for switching, inhibition, and working memory. As a result, classifying tests as attention tests and executive tests can be difficult. 18,21 Mental processing speed can also be considered to have both an attentional and an executive component. Disorders Associated with Attentional Deficits Attention cannot be localized to a specific brain area, but rather a network of multiple brain systems interacts to control the many aspects of attention. 22 This network includes the inferior parietal cortex, dorsolateral prefrontal cortex, orbital frontal region, limbic system structures, subcortical systems, and midbrain systems Given the many different circuits underlying attention, it is easy to understand why attentional deficits are commonly seen across a wide range of neurologic conditions. Disorders of attention are quite common secondary to damage to a variety of subcortical or cortical brain structures or to psychiatric illness. 25 Some of the more common disorders in which attention is significantly affected include ADHD, TBI, stroke, dementing conditions (eg, Lewy body dementia), and hydrocephalus. 25 Diminished attentional abilities are also a common secondary feature of most psychiatric conditions and are considered the most common cognitive deficit associated with major affective disorders. 25 Measures of Attention Common attentional measures are listed in Table 1. 12,26 32 The evaluation of attention begins with behavioral observations of the patient designed to assess the most basic levels of attention, including arousal (eg, Is the patient conscious? Can the patient be awakened if sleeping?). Arousal is defined as a state of general alertness and is necessary for examination of higher cortical functions. When meeting a patient, the Hospital Physician Board Review Manual

7 neuropsychologist notes whether the patient looks at the examiner on entering the room and/or scans the new environment. The examiner also notes whether the patient can be engaged in conversation or is able to orient to tasks when directed. A frequently used measure to assess basic visual attention and tracking is the Trail Making Test, Part A. 29 On this measure, the individual is presented with randomly arrayed numbers on a page that they are asked to rapidly connect in sequential order by drawing a line between them (ie, in dot-to-dot fashion). This task can also be considered an executive measure as it taps sequencing abilities. Performance is based on time to complete the task, with sequencing errors also noted. Neuropsychologists assess attention span, or attentional capacity, in both verbal and visual domains. This aspect of attention refers to the amount of unrelated information an individual is able to process and hold for a brief interval until a response is required. In normal individuals, it has long been appreciated that normal span of attention is 7 plus or minus 2 pieces of information, referred to as the magic number. 33 In the verbal modality, attention span is typically measured by asking a patient to repeat increasingly longer sequences of random digits read aloud (WAIS-IV Digit Span Forward). 12 In the visual modality, attention span is often measured by the ability to repeat increasingly longer patterns of tapping sequences on a board of randomly arrayed blocks (Wechsler Memory Scale [WMS]-III Spatial Span Forward). 19 Working memory, the ability to hold information in mind while performing a mental operation on it (also considered an aspect of executive functioning), is frequently assessed by asking the individual to rearrange information immediately after it is presented. For example, the second part of the Digit Span subtest presents increasingly longer sequences of digits that the patient is asked to recite back to the examiner in reverse order of presentation, and the most recent version of the WAIS(IV) 12 includes a task in which the patient is asked to reorder randomly ordered numbers into a consecutive sequence. Another frequently used measure of verbal working memory requires patients to mentally rearrange a series of randomly presented numbers and letters into numerical and alphabetical order (WAIS-IV Letter-Number Sequencing). 12 Visual working memory is similarly assessed, with the patient required to tap out a presented sequence in reverse order of presentation. Selective attention is the ability to attend to a specific stimuli in the face of distractions. The Stroop Color and Word Test assesses selective attention by asking the patient to selectively attend and respond to 1 type of stimuli (colors) and ignore and inhibit responses to another type of stimuli (printed words). Another measure of selective attention is the Brief Test of Attention. 27 In this test, the patient hears a series of numbers and letters and is asked to track the amount of 1 stimulus type (numbers or letters) while ignoring competing stimuli. Sustained attention, or vigilance, is considered the ability to maintain active attention to stimuli over time. Measures used to assess sustained attention generally employ a target detection paradigm within a continuous performance measure. These tasks require the patient to monitor a continuous presentation of stimuli over an extended time period and to rapidly respond to prespecified target stimuli but not to nontarget, distracter stimuli. Performance is measured in terms of accuracy and reaction time. In regards to accuracy, a high rate of omission errors is suggestive of inattention, while a high rate of commission errors (incorrectly responding to the distracter) is suggestive of impulsivity. Response time is measured for overall rate as well as consistency, with variable and slowing response rates across the test generally suggestive of inattention. Spatial attention refers to the ability to allocate visual attention to space. Individuals with lateralized lesions, particularly in the parietal or temporal cortices, may exhibit a type of spatial inattention called hemineglect whereby perceptual information that is presented on the side of the body contralateral to the lesion is ignored. 34 Hemineglect is more common in individuals with right- than left-sided lesions and can be visual, auditory, or tactile. 35 It also can be dramatic or more subtle in nature depending on the neurologic insult and/or time passed since the injury. Cancellation tasks are commonly used to assess spatial hemineglect. These tasks require the patient to detect and cancel (ie, cross out) target stimuli among an array of visually similar stimuli. Other tests of visual neglect include line bisection tasks, drawing and copying tests (eg, a clock face with numbers or a daisy), and reading tests (particularly useful when the elicitation of a motor response is not possible, for example, due to hemiparesis). 5 FRONTAL/EXECUTIVE FUNCTIONING The frontal lobes are responsible for higher order, complex cognitive abilities, including executive functioning, social intelligence (comportment, empathy, insight, judgment), and motivation. 36 The frontal lobes are the largest region of the brain, comprising one third of the human cortex, and are divided into 3 circuits: the dorsolateral circuit, the orbital prefrontal circuit, and the anterior cingulate circuit. Executive functioning is thought to be largely governed by the dorsolateral prefrontal circuit Neurology Volume 13, Part 3

8 Table 2. Common Measures for the Assessment of Frontal/ Executive Functions Component Assessed Initiation and set maintenance Cognitive flexibility Organization and planning Reasoning/abstract reasoning Behavioral inhibition Apathy, disinhibition, executive functioning (rating scales: patient, informant) Common Measures Used Controlled Oral Word Association Test (COWAT), 40 Animal Fluency, Verbal Fluency, Design Fluency (D-KEFS 31 ) Trail Making Test Part B, 29 Trail Making Test Letter-Number Sequencing, Condition 4 (D-KEFS), Wisconsin Card Sorting Test (WCST) 41 Rey-Osterrieth Complex Figure, 42 Tower of London Test, 43 Tower Test (D-KEFS), California Verbal Learning Test-II (CVLT-II) 44 Similarities (WAIS-IV 12 ), Matrix Reasoning (WAIS-IV), Proverb Test (D-KEFS) Stroop Color and Word Test 32 (Interference Conditions), Go/No-Go tasks Frontal Systems Behavior (FrSBe) scale, 45 Behavior Rating Inventory of Executive Function (BRIEF) 46 D-KEFS = Delis-Kaplan Executive Function System; WAIS = Wechsler Adult Intelligence Scale. and is characterized by the ability to formulate goals with regard to long-term consequences. It includes the ability to generate multiple response alternatives, select and initiate goal-directed behaviors, self-monitor responses and behavior, modify behavior and shift set quickly in response to change, and persist with tasks despite distraction. 37 The orbital prefrontal circuit is crucial for inhibitory processes that guide social behavior and enable behavioral comportment, and the anterior cingulate circuit is important for initiation and motivation. 37 Disorders Associated with Frontal Impairment Frontal functions are carefully assessed in a neuropsychological evaluation as they are often impaired in neurologic and psychiatric patients. Frontal cortex is susceptible to the effects of aging and is vulnerable to many causes of brain damage. 7 The frontal lobes are comprised of networks that lead to subcortical structures such as the striatum, globus pallidus, substantia nigra, and thalamus. 5,38,39 Neurologic disorders that affect these structures can present with cognitive and behavioral impairments similar to those seen with lesions of the frontal cortex. 37 Types of neurologic dysfunction that typically result in some deficit of frontal/executive abilities include ADHD, TBI (in which the frontal lobes are particularly susceptible to injury), stroke, Huntington s disease, and certain dementing illnesses (eg, frontotemporal dementia, Lewy body dementia, Parkinson s disease dementia, vascular dementia). Frontal impairment is often characterized by behavioral disinhibition, impulsivity, apathy, and/or lack of insight. Measures of Executive Functions Most neuropsychological measures examining frontal functions are designed to assess the dorsolateral prefrontal circuit, which governs executive abilities (Table 2). 12,29,31,32,40 46 Executive functions are often assessed on tasks that are complex and somewhat unstructured in nature, requiring that the patient employ skills such as initiating, sustaining, shifting, planning, and organizing behavior in order to successfully complete the task presented. Abstract reasoning can also be considered an executive, higher order function that involves understanding theoretical concepts or using logic to solve a problem or task. The WAIS-IV Similarities subtest 12 is one measure designed to evaluate abstract reasoning. In this task, the patient is asked to determine how 2 seemingly dissimilar items are alike. The ability to initiate and sustain behavior is an important aspect of executive functioning. It is typically assessed through fluency tests where the patient is asked to rapidly generate responses to a particular cue. For example, in the letter fluency task patients are given 1 minute to rapidly generate as many words as they can that begin with a particular letter. Patients with frontal dysfunction can have difficulty with this task due to problems with initiation of responses, task persistence, the ability to generate different answers, and/or getting stuck on a particular response (also known as perseverative responses). Difficulties on this task can also arise due to a more primary language disorder. Cognitive flexibility refers to the ability to shift to an entirely separate task or to alternate between different stimuli. Commonly used measures of cognitive flexibility are Part B of the Trail Making Test 29 and condition 4 of the Delis-Kaplan Executive Function System (D-KEFS) 31 Trail Making Test. These tasks require the ability to rapidly alternate between 2 sequences, such as numbers and letters. Performance on this measure is compared with performance on straightforward sequencing measures that do not have the additional shifting component (eg, Trail Making Test, Part A, 29 which only requires rapid sequencing of numbers in consecutive order). A considerable performance difference between these 2 conditions (ie, slower response rate or failures to shift set on Part B) suggests impaired cognitive flexibility. Problem-solving measures, such as the Wisconsin Card Sorting Test, 41 can also be used to evaluate cognitive flexibility. On this task, the patient is asked to sort cards that include symbols that vary in color, shape, and number. The individual is not told Hospital Physician Board Review Manual

9 how to sort the cards but rather must deduce the sorting categories based on limited and changing corrective feedback. Difficulty in shifting set on this measure is evidenced by failure to change the sorting criteria in response to corrective feedback; instead, the patient repeatedly provides the once correct response despite the change in task demands (perseveration). Planning and organization are assessed by evaluating a patient s ability to develop an efficient approach to completing a relatively open-ended task. Tower tasks (Tower of London Test, 43 D-KEFS Tower Test 31 ) examine spatial planning and rule-learning skills by asking a patient to complete the task in the least amount of steps. Information regarding the patient s organizational and strategic ability can also be gathered from memory tasks, such as list-learning measures (California Verbal Learning Test- II) 44 in which words from several different semantic categories (eg, furniture, animals) are presented in random order. The patient with good organizational strategies detects and uses this semantic categorization to their advantage, using semantic clustering to assist with learning and recall rather than relying on less strategic serial clustering strategies. In evaluating the patient s performance, the neuropsychologist considers not only how many words are learned and remembered, but also what strategies the patient employs. Similarly, within the visual modality, patients are asked to copy a complex figure, such as the Rey-Osterrieth Complex Figure, 42 with both the accuracy of the rendered figure and the individual s planning and organizational approach evaluated. On both of these tasks, individuals with impaired executive functioning typically fail to employ an organized strategic approach, which can impact later memory for the information. The orbital prefrontal circuit is important for inhibitory processes that guide social behavior. Inhibition may be assessed through measures such as the Stroop Color and Word Test 32 or Go/No-Go tasks, which are measures of cognitive control that assess the ease with which a person can maintain a goal in mind and suppress a habitual response in favor of a less familiar one. 18,47 Go/ No-Go tasks, for example, require a patient to respond to a go signal and withhold or inhibit the response to the no-go signal. Additionally, social inhibition can be examined through measures that assess behavioral problems, specifically disinhibited behavior. The anterior cingulate circuit, important for initiation and motivation, can be assessed through fluency tasks (which have an initiation component), careful observation of behavior during the evaluation, patient and family report, and behavioral rating scales. Self and family reports are obtained through clinical interview and additionally through responses on behavioral inventories. The Frontal Systems Behavior (FrSBe) scale 45 is a commonly utilized behavioral inventory that samples behaviors associated with different prefrontal (dorsolateral, orbital, and anterior cingulate) circuits and provides scores reflecting endorsements in 3 associated behavioral domains (executive dysfunction, disinhibition, and apathy). Other behavioral inventories include the Behavior Rating Inventory of Executive Function (BRIEF) 46 and the Behavioral and Psychological Assessment of Dementia (BPAD). 48 On these measures, the patient (on selfrating scales) and/or family member/collateral informant (on the informant scales) answer questions about a range of typical frontal-executive type behaviors. Often, as on the FrSBe scale, family members/collateral informants are asked to rate the patient s behavior both before and after onset of difficulties to help provide an indication of behavior change relative to premorbid presentation. For example, it is important to differentiate between the patient who always had a fiery temper from the patient who had been easy going and only now curses and is quick to anger. Rating scales such as these provide important information regarding a patient s behaviors in their daily life that can be difficult to obtain during the clinical interview or through testing. These scales also provide a means of quantifying and monitoring behavioral symptomatology. Family as well as self-rating inventories are particularly helpful as patients with frontal impairment often exhibit diminished insight into their deficits. 49 MEMORY A formal memory assessment divides memory into component parts, including encoding (or acquisition), consolidation (or storage), and retrieval, as difficulties with these different parts of memory performance are associated with specific neural networks and underlying etiologies. There are also differing types of memory, each presumed to be mediated by different neural systems. In general, episodic memory (autobiographical memory for personally experienced events) is thought to involve the medial temporal lobes, semantic memory (the general store of conceptual or factual knowledge, such as the color of a specific animal or the first president of the United States) is thought to involve the inferolateral temporal lobes, and procedural memory (automatic behavioral and cognitive skills, such as riding a bicycle) is thought to involve the basal ganglia and other structures. 50 In neuropsychological evaluations, the focus is typically on a patient s difficulty remembering newly learned episodic information. Impaired memory for episodic information learned after an injury is called anterograde amnesia and is seen in conditions that primarily disrupt the medial temporal lobe system, which includes the Neurology Volume 13, Part 3

10 Table 3. Common Measures for the Assessment of Memory Component Assessed Verbal memory Visual memory Enhanced encoding and retrieval Remote/long-term memory Common Measures Used California Verbal Learning Test (CVLT-II), 44 Consortium to Establish a Registry for Alzheimer s Disease (CERAD) 55 word list, Hopkins Verbal Learning Test Revised (HVLT-R), 56 Verbal Paired Associate Learning (WMS-IV 57 ), Logical Memory (WMS-IV), Rey Auditory Verbal Learning Test 58 Visual Reproduction (WMS-IV), Brief Visual Memory Test Revised (BVMT-R), 59 Rey-Osterrieth Complex Figure Test, 42 Figure Recall (RBANS 60 ), Face Recognition (WMS-III 26 ) Free and Cued Recall Test 61 Information (WAIS-IV 12 ), Famous Faces Test, 62 Information and Orientation (WMS-III), Autobiographical Memory Interview 63 RBANS = Repeatable Battery for the Assessment of Neuropsychological Status; WAIS = Wechsler Adult Intelligence Scale; WMS = Wechsler Memory Scale. hippocampus and related structures (eg, parahippocampal gyrus, entorhinal cortex, fornix, amygdala) as well as other brain structures with which it has rich interconnections (eg, thalamus, basal forebrain). 51 Dense amnesia is typically indicative of bitemporal brain damage. Implicit memory functions, such as priming, skill learning, and conditioned responses, are typically intact in anterograde amnesia and are usually not assessed within a neuropsychological evaluation. Retrograde amnesia refers to loss of information learned before an injury. It is extremely rare in the absence of anterograde amnesia and is somewhat more difficult to evaluate within a neuropsychological assessment. However, it can be ascertained by asking patients about general semantic knowledge, public events, or their own personal history. Disorders Associated with Memory Impairment It is important to characterize memory difficulties, as they can be caused by difficulties in areas outside of the memory domain. For example, an individual may have trouble remembering information because new learning is impacted by concentration or attentional difficulties, whereas another patient may exhibit a first order memory impairment, characterized by difficulty storing new information. Individuals with Alzheimer s disease commonly display impairment across the memory spectrum and have specific deficits in delayed memory that are not aided by cueing or recognition because the information was presumably never consolidated. Disruption of medial temporal functioning impairs the ability to consolidate new information into memory, while dysfunction of the frontalstriatal brain systems can cause impaired strategic memory. 5 The frontal lobes aid in the registration or encoding of information, the retrieval of information without cues, and the recollection of the source of the information. Thus, patients with frontal dysfunction often have difficulty with strategic aspects of memory, including impaired ability to attend to or organize information or to retrieve information that has been adequately stored. In fact, retrieval-based memory deficits are the hallmark of memory disturbance associated with subcortical dementias that affect executive functioning (eg, Parkinson s disease dementia, dementia related to Huntington s disease, multiple sclerosis). 5,52,53 Memory problems can also be observed in other neurologic conditions in which the limbic system is impacted, including Wernicke-Korsakoff syndrome, anoxic brain damage, TBI, infarctions in the posterior cerebral artery, and limbic encephalitis. 54 A common referral question posed to neuropsychologists is whether a patient s memory impairment is due to depression or a dementing illness. Although all domains must be carefully examined in order to make a diagnostic interpretation, some patients with depression have attentionally based memory problems affecting the amount of information they are able to encode as well as their ability to conduct a strategic search of memory. Depression is not, however, associated with consolidation deficits. Measures of Memory The evaluation of memory includes administration of measures that provide information about each of the components of memory, with different patterns of intact and impaired components suggesting different etiologies. Common measures used to evaluate memory are illustrated in Table 3. 12,26,42,44,55 63 Typically, these measures present the patient with novel information and then test the encoding, consolidation, and retrieval of the information in the form of immediate recall, delayed recall, and recognition tasks. The WMS, currently in its fourth edition (WMS-IV), 57 includes measures in which information is presented verbally through wordpair associates or narrative stories and visually through designs. Additional measures such as the Free and Cued Selective Reminding Test 61 and the California Verbal Learning Test-II 44 examine free recall of verbal material compared to recall with cues. This information is used to determine whether memory difficulties are more frontally mediated (cueing aids in retrieval) or stem from a hippocampal disturbance (where cueing would not be 10 Hospital Physician Board Review Manual

11 expected to significantly aid retrieval). Narrative stories, (eg, Logical Memory [WMS-IV]) 57 are also beneficial in making this distinction as they provide added structure, which is often helpful to patients with frontally mediated memory trouble but is less helpful for individuals with frank anterograde amnesia. As in other domains, the neuropsychologist also typically includes assessment within verbal and visual modalities, as individuals with unilateral medial temporal lobe dysfunction can exhibit material-specific memory impairment (ie, with rightsided lesions resulting in greater impairment of visual than verbal information and the opposite patterns seen in individuals with left-sided lesions). 64 Retrograde amnesia is typically temporally graded (ie, Ribot s Law), with remote memories more resistant than recently acquired memories. 50,54 Measures that assess remote memory for personal or public information ask questions about well-known events that occurred during different decades as well as questions about more recent personal experiences (ie, from childhood through adulthood). Of course, there are challenges to assessing remote memory. First, the neuropsychologist has no information regarding the individual s personal experiences and has to rely on corroboration from collateral informants. Assessing a patient s remote information concerning public events is also complicated, as it is difficult to know what information the individual initially registered about the event. Remote memory measures try to manage this by including events that were prominent in the news as well as those that were less well known. Evaluating the patient s performance across both well-known and less well-known events, evaluating whether there is a temporal gradient in their loss of memory, and utilizing information about premorbid status (ie, educational history) together can help determine the extent of a patient s remote memory loss. Although focal retrograde amnesia can accompany damage to the anterior temporal lobes, basal frontal lobe, and brainstem, remote memory deficits can also have a psychiatric etiology (ie, dissociative amnesia). LANGUAGE Knowledge and the ability to use language underlie the ability to communicate, specifically the ability to understand and convey information, whether about ideas, feelings, or needs. Although language is a highly complex, rule-governed system that includes the analysis of sounds, words, morphology, syntactic structures, and discourse, most individuals are able to use this system with a high degree of facility, with differences mainly in the size of one s vocabulary knowledge rather than in the basic ability to comprehend and express oneself through language. Its importance to human cognitive capacity is perhaps reflected in the fact that the left hemisphere, in which language is lateralized for the majority of individuals (98% of right-handed individuals and 60% 65% of left-handers), is referred to as the dominant hemisphere because of its language specialization. 65 Within a neuropsychological evaluation, the centrality of language is evident in the fact that the patient s ability to engage in the evaluation relies heavily on language competence, even when the measures themselves do not directly assess language abilities. Test instructions and questions are usually presented verbally, and patients often provide responses verbally. Thus, even when a neuropsychologist is not administering a specific language test, information can be gathered about a patient s ability to comprehend information and to produce appropriate responses. Determining which aspects of language knowledge and use are preserved for a patient is important for functional reasons and for diagnostic purposes. This information is used to guide therapeutic interventions and recommendations regarding functional communication skills. This information also can be applied for diagnosis since the breakdown of language is often highly specific for lesion sites as reflected by the association of different clinical aphasia syndromes (eg, Broca s aphasia, Wernicke s aphasia) with specific lesion sites. Although such aphasia syndromes continue to be referred to and are helpful in providing a general picture of impaired and spared language functions, recent research points to a more variable pattern of the association between lesion sites and language impairments. 66 Measures Used to Assess Language When language is not a specific area of deficit, language measures mainly focus on language at the singleword level. Evaluations at this level include measures of vocabulary comprehension (eg, word-picture matching tasks, such as the Peabody Picture Vocabulary Test-4, 67 and word definition tasks, such as the WAIS-IV Vocabulary subtest 12 ), measures of expressive single-word abilities (eg, confrontation naming such as the Boston Naming Test), 68 and a measure of single-word reading. Table 4 lists common measures used to assess areas of language competence. 12,67 70 Measures that assess reading can be used to estimate premorbid intelligence (eg, North American Adult Reading Test 16 ). These measures often include words that are irregularly spelled (eg, ballet, gauche), with patients ability to correctly pronounce these words reflecting their level of familiarity with a range of written vocabulary rather than phonologic decoding abilities. Also, as described above, vocabulary Neurology Volume 13, Part 3 11