Chapter 6. Neuropsychological Assessment of Late-Life Cognitive Disorders
© American Psychiatric Publishing
Alzheimer’s disease (AD) is by far the most common neurocognitive disorder of aging. Affecting nearly 10% of the population over age 65 years, AD is estimated to have a prevalence of 25%–40% in individuals who are age 85 years or older (Hebert et al. 2013). Because of its slow and insidious onset, the early stages of AD can be confused with relatively benign memory impairments associated with normal aging.
Advances in disease biomarkers for AD have led to changes that bolster diagnostic confidence over the course of the disease (Albert et al. 2011; McKhann et al. 2011; Sperling et al. 2011). At present, AD biomarkers in an asymptomatic individual are confined to research use because these indicators do not currently provide reliable information at the individual levels as to whether symptoms will develop and over what time frame. In this new diagnostic context, neuropsychological assessment continues to play a central role in the diagnosis of neurocognitive disorders, in the detection of mild neurocognitive disorders likely to transition to a more fully expressed syndrome (Gomar et al. 2011), and in the differentiation among the plethora of cognitive disorders that can interfere with functional ability and quality of life (Knopman et al. 2001; Weintraub et al. 2012). The neuropsychological assessment offers a sensitive, reliable, and noninvasive approach to early symptom verification as well as a potentially cost-effective means for managing patients with memory disorders (Welsh-Bohmer et al. 2003).
Our goals in this chapter are 1) to describe in detail the instances in which neuropsychological assessment can be most useful in geriatric settings, 2) to discuss the neuropsychological examination process and common instruments applied in this context, and 3) to summarize the neurobehavioral presentations of common disorders in geriatric practices, specifically the profiles of normal aging, various common neurocognitive disorders of later life, and depression.
Neuropsychological Assessment in Geriatric Settings
Memory complaints in later life are common, often reflecting the effects of normal aging of the nervous system. An acute public awareness of AD heightens the fear that relatively benign changes in speed of processing and word retrieval are a harbinger of an imminent major neurocognitive disorder. Drawing the line between healthy aging and early brain disease is difficult. The inclusion of fluid and imaging AD biomarkers in the diagnosis of the disease may provide more clarity in a variety of situations where there is diagnostic ambiguity. Diagnosis of major or mild neurocognitive disorder due to AD begins with the identification of the clinical phenotype and the exclusion of reasonable medical explanations. Consideration of cerebrospinal fluid biomarkers of the two proteins implicated in AD, amyloid-β peptide and tau, along with structural and functional neuroimaging studies, secures the diagnosis of either early- or later-stage AD (Albert et al. 2011; McKhann et al. 2011; Sperling et al. 2011).
Despite the advances in useful disease biomarkers, a diagnosis of AD continues to rest heavily on clinical assessment of the presenting syndrome. With early symptomatic disease and the presence of significant disease comorbidities, each of which can interfere with cognition and function, neuropsychological assessment may be needed. In geriatric practices, patients are referred for neuropsychological evaluation for four common reasons, which are not mutually exclusive. The first and by far most frequent reason for referral is to assist in the diagnosis of a cognitive disorder. Specifically, the examination is used to verify the presence or absence of a cognitive syndrome (e.g., major or mild neurocognitive disorder) and to determine the likely differential diagnostic possibilities based on the behavioral profile (e.g., AD vs. vascular neurocognitive impairment). The second reason for neuropsychological testing is to establish an objective baseline for purposes of tracking changes in mentation over time; this baseline is useful in clarifying diagnostic assignments due to neurodegenerative diseases such as AD in which the establishment of progression is essential. The neuropsychological examination in this context can also be used to monitor treatment response. A third common referral reason for testing is to guide clinical care decisions, including the determination of functional capacities and competency (see Koltai and Welsh-Bohmer 2000). Issues typically confronted by a geriatric evaluation include medication management and a patient’s ability to live independently, manage finances, and drive safely. Finally, the neuropsychological evaluation can be used to guide appropriate therapeutic interventions. Based on the results of testing, identified cognitive strengths and weaknesses can be used for designing appropriate rehabilitation approaches, such as those involving compensatory strategies or psychotherapy (for full discussion, see Attix and Welsh-Bohmer 2006).
The actual neuropsychological evaluation process can vary in form across clinical practices, depending in part on the populations typically served (e.g., a Spanish-speaking population vs. native English speakers) and in part on the training emphasis of the neuropsychologist administering the examination. The approach can use a fixed battery or may use more flexible methods tailored to the referral issue. Regardless, there are standard features that are applied uniformly across neuropsychological settings to ensure that all testable areas of cognition are assessed (Lezak et al. 2012). The evaluation typically begins with a diagnostic interview to identify the major referral issues and obvious symptoms. In this interview, a patient’s orientation to situation, language, behavioral organization, memory, mood, and affect are observed within a naturalistic context. With patient consent, family members generally are also interviewed separately to determine changes in functional ability and to clarify historical and medical information. In the formal testing session, 10 central domains of cognition and behavior are generally assessed: orientation, intelligence, language expression and comprehension, episodic learning and memory, attention and concentration, higher executive functions, visuoperception, constructional, and spatial abilities, sensorimotor integration, personality and behavior, and mood and anxiety. Neuropsychological tests that are commonly used to assess these various functional domains are listed in Table 6–1. From the battery of tests, a profile of performance can be constructed, examined in reference to normative standards, and then interpreted relative to the established behavioral profiles of known neurobehavioral syndromes.
Neuropsychological Assessment in Geriatric Settings Common neuropsychological tests used in geriatric assessment
Domain | Tests commonly used | References |
|---|---|---|
Orientation/global mental status
|
Mini-Mental State Examination
| |
Montreal Cognitive Assessment
|
Nasreddine 2010
| |
Alzheimer’s Disease Assessment Scale—Cognitive
| ||
Intellect
|
Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV)
|
Wechsler 2009a
|
Language
|
Category/semantic fluency (e.g., animal fluency)
|
Strauss et al. 2006
|
Lexical fluency (e.g., FAS test or Controlled Oral Word—CFL test)
| ||
Boston Naming Test
| ||
Multilingual Naming Test
| ||
Memory
|
Wechsler Memory Scale, 4th Edition (WMS-IV)
| |
California Verbal Learning Test, 2nd Edition
| ||
Hopkins Verbal Learning Test—Revised
| ||
Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Test
|
Welsh-Bohmer and Mohs 1997
| |
Rey Auditory Verbal Learning Test
| ||
Brief Visuospatial Memory Test—Revised
| ||
Buschke Selective Reminding Test
|
Strauss et al. 2006
| |
Attention/concentration
|
Subtests from the WMS-IV and WAIS-IV
|
Lezak et al. 2012
|
Executive function
|
Trail Making Test
| |
Color Trail Making Test
| ||
Stroop Color and Word Test
| ||
Symbol Digit Modalities Test
| ||
Short Category Test
| ||
Wisconsin Card Sorting Test
| ||
Visuoperception
|
Benton Facial Recognition Test
| |
Judgment of Line Orientation Test
| ||
Tests of Constructional Praxis
|
Lezak et al. 2012
| |
Sensorimotor abilities
|
Grooved Pegboard
|
Strauss et al. 2006
|
Finger Oscillation
| ||
Personality and behavior
|
Minnesota Multiphasic Personality Inventory—2
| |
Frontal Assessment Battery
| ||
Mood and anxiety
|
Geriatric Depression Scale
| |
Beck Depression Inventory–II
| ||
Beck Anxiety Inventory
|
Simplifying the geriatric assessment are several neuropsychological batteries designed for use with elderly patients and the availability of appropriate normative information (for a review, see Strauss et al. 2006). Among these are the Mattis Dementia Rating Scale (Mattis et al. 2002) and the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer’s Disease (Morris et al. 1989). Both assessments are relatively brief and sensitive to early stages of AD neurocognitive disorder. Additionally, they both offer presentation formats, such as the use of large print and an oral format, to minimize the influences of sensory confounding (see Welsh-Bohmer and Mohs 1997). The Neuropsychological Assessment Battery is another measure that provides a broad assessment of key domains with normative information for individuals ages 18–97 years (Stern and White 2003). Although not specifically designed for the geriatric population, this instrument has the advantage of co-normed subtests, simplifying interpretation of performance across tests.
It must be emphasized that the neuropsychological examination is not simply a process of actuarial comparisons to normative tables. The neuropsychological evaluation, as with other forms of clinical diagnosis, rests on an inferential process. The neuropsychological diagnosis is an iterative process that incorporates multiple sources of information to arrive at diagnostic impressions (see Potter and Attix 2006). In assessing a geriatric patient, the psychologist must first determine the patient’s likely premorbid ability to determine whether any observed changes are newly acquired for that individual or reflect long-standing weaknesses. Once this has been established, the presence of cognitive impairment is determined in reference to appropriate normative values from similarly aged individuals with comparable education level or intellectual function (Steinberg and Bieliauskas 2005). Consideration is given to any potential confounding influences to test performance, including subject motivation factors, extratest factors (e.g., interruptions), and other test behaviors that might interfere with optimal function (e.g., anxiety). The interpretation of the likely medical and psychological contributions to the cognitive profile requires a good appreciation of brain-behavior organization. The neuropsychologist must consider whether the results obtained make sense from a functional anatomical perspective and then analyze the profile to determine its conformity to known neurobehavioral syndromes, such as normal aging, mild neurocognitive disorder, AD, and depression. Before final diagnostic determination, consideration is given to other attendant data, such as medical history, ancillary studies (including imaging data), and informant report of functional change. The combined information is more useful in differentiating normal aging from early neurocognitive disorder and improves diagnostic accuracy (Tschanz et al. 2000). The next sections of this chapter summarize the neuropsychology of normal aging and the differentiation of various common forms of late-life neurocognitive disorder. Separately from this, we also consider in some detail the neuropsychology of geriatric mood disorders and the contribution of depressive disorders to the presentation of neurocognitive disorders.
Neuropsychology of Normal Aging
Cognitive complaints are both more frequent and more worrisome in later adulthood, given the high age-associated prevalence of neurodegenerative conditions. However, comparisons of cognitive performance across the adult age span (20–80 years) illustrate incremental declines with advancing age across many cognitive domains (Drachman 2006; Finch 2009; Salthouse 2009). Compared with young adults, older individuals show selective losses in functions related to speed and efficiency of information processing. Particularly vulnerable are memory retrieval abilities, attentional capacity, executive skills, and divergent thinking such as working memory and multitasking (Samson and Barnes 2013; Salthouse 1996; van Hooren et al. 2007). On formal neuropsychological testing, memory measures involving delayed free recall are typically affected (Craik and Rose 2012), although not to the pronounced extent found in AD (Welsh et al. 1991). Unlike individuals with neurocognitive disorder due to AD, older adults without neurocognitive disorders typically demonstrate intact memory ability on tests such as cued recall and delayed recognition. This profile of performance suggests different mechanisms underlying the memory loss of normal aging and AD. In AD, the problem appears to involve the consolidation or storage of new information into long-term memory stores. In normal aging, the principal problem appears to be primarily in the efficient accessing of recently stored information. Therefore, procedures providing structural support for recall (e.g., recognition) facilitate the retrieval process. In addition to having a decline in memory, normal older individuals also show some decrements compared with younger cohorts on tests of visuoperceptual, visuospatial, and constructional functions (Eslinger et al. 1985; Howieson et al. 1993; Park and Schwarz 1999). These modest declines are seen on tests involving visual analysis and integration, such as the Block Design subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV; Wechsler 2009a), and similar integrative tests involving visual processing. Performance on measures of executive control (e.g., Trail Making Test; Reitan and Wolfson 2004), language retrieval (e.g., verbal fluency), and divided attention (e.g., Digit Span subtest from WAIS-IV) also tends to be lower in older groups compared with their younger counterparts (Salthouse 2010).
A number of explanations for age-related cognitive change have been suggested, none of which are mutually exclusive. All basically support a premise of a broad explanatory mechanism for age-related cognitive change rather than unique and specific changes in restricted cognitive domains. Speed of central processing has been one popular unifying notion, given that the majority of tasks affected in aging involve motor responses or reaction times (Salthouse 2005). Empirical studies support slowed central processing as a leading explanation for cognitive change with aging (Finkel et al. 2007). Another explanation posits that the profile of cognitive change in normal aging is the result of a loss in fluid abilities—that is, skills that require novel problem solving and flexible thought (Botwinick 1977; Horn 1982); by contrast, well-rehearsed verbal abilities—so-called crystallized skills—are less susceptible to age-associated change. Refinements of this hypothesis have conceptualized normal aging as a selective vulnerability in frontal, dysexecutive processes (Daigneault and Braun 1993). This notion is consistent with the behavioral difficulties observed, suggesting subtle impairments in integrative and retrieval functions, and is also supported by neuroimaging (Coffey et al. 1992; Gur et al. 1987; Langley and Madden 2000; Tisserand 2003) and histopathological findings (Haug et al. 1983) within the frontal-subcortical brain connections. Although this hypothesis is conceptually appealing and capable of explaining much of the observed change with aging, some work suggests that the deficits may not be localizable in their entirety to a single brain system. Rather, cognitive decline is conceptualized as a process occurring across the lifespan, involving failures in distributed brain networks (Finkel et al. 2007; Reuter-Lorenz and Park 2010; Salthouse 2010). A significant problem in the interpretation of the earlier studies is that many did not routinely screen for nervous system disorders or operationalize their criteria for normal aging. Work continues to identify the nature of the mechanisms that underlie age-related cognitive change and the association of these mechanisms with brain diseases common to aging, specifically AD (Reuter-Lorenz and Park 2010; Samson and Barnes 2013).
Differentiating Common Forms of Neurocognitive Disorder in Late Life
AD is the leading cause of late-life neurocognitive disorder, accounting for 50%–75% of all cases identified within community-based cohort and population-based series (Breitner 2006; Ebly et al. 1994; Gascón-Bayarri et al. 2007). Vascular neurocognitive disorder occurs either alone or in combination with AD in 12%–30% of the cases (Lobo et al. 2000; Román 2003), whereas neurocognitive disorder with Lewy bodies accounts for 3%–26% of the cases (Lippa et al. 2007; McKeith et al. 2005; Zaccai et al. 2005). Rare disorders of late life, such as frontotemporal lobar degeneration, account for an additional 3%–5% of the reported cases of neurocognitive disorders (Cairns et al. 2007; Johnson et al. 2005). Illnesses such as hydrocephalus, metabolic disorders, and infectious diseases are etiologically tied to the remaining cases (Holman et al. 1995; Savolainen et al. 1999). The cognitive profiles of the various neurocognitive disorder subtypes are to some extent overlapping, but there are unique features to many of them that can be of diagnostic utility. These characteristics are summarized in Table 6–2.
Differentiating Common Forms of Neurocognitive Disorder in Late Life Clinical neurocognitive syndromes and associated neuropsychological profiles
Neurocognitive syndrome and characteristics | Neuropsychological profile | Examples of tests fit for purposea |
|---|---|---|
Normal aging | ||
Subjective memory complaints
Annoying but not disabling problems
Frequent problems with name retrieval
Minor difficulties in recalling detailed events
|
Impaired fluid abilities (novel problem solving)
Deficiencies in memory retrieval
Decreased general speed of processing
Lowered performance on executive tasks and visuospatial skills/visuomotor speed
|
WAIS-IV Performance IQ tests
Lexical fluency, immediate recall of word lists
Speeded tests from WAIS-IV
WAIS-IV Digit Span Backward, Trail Making Test
Symbol substitution tasks
|
Mild cognitive impairment—amnesic form | ||
Subjective memory complaints
Noticeable change in memory as noted by informants
Clinical Dementia Rating score of 0.5 (mild, questionable dementia) (Hughes et al. 1982)
Problem not disabling
|
Memory performance 1.5 SD below age-matched peers
Otherwise intact neurocognitive function or only minimal losses (< 1.5 SD)
Functional disorder limited to mild interference from the memory difficulty
|
Wechsler Memory Scale, 4th Edition
CVLT-II
Rey Auditory Verbal Learning Test
Hopkins Verbal Learning Test—Revised
Buschke Selective Reminding Test
|
Alzheimer’s disease | ||
Insidious onset
Progressive impairment
Prominent memory impairment
Possible disorders: aphasia, apraxia, agnosia
|
Impaired memory consolidation with rapid forgetting
Diminished executive skills
Impaired semantic fluency and naming
Impaired visuospatial analysis and praxis
|
Particularly episodic memory tests (e.g., CVLT-II, Brief Visuospatial Memory Test—Revised) and tests of novel problem solving and abstraction (WAIS-IV), Trail Making Test, WAIS-IV Digit Span, constructional praxis (copying of figures)
|
Frontotemporal neurocognitive disorder | ||
Prominent personality/behavioral change
Disinhibition or apathy
Impaired judgment/insight
Normal mental status initially
|
Pronounced executive impairments
Cognitive inflexibility
Impaired sequencing
Perseverative, imitative, utilization behaviors
Poor use of feedback
Prone to interference
Less obvious memory impairments
|
Wisconsin Card Sorting Test
Short Category Test
Stroop Color Word Test
Frontal Assessment Battery
|
Lewy body neurocognitive disorder
| ||
Fluctuations in alertness/acute confusional state
Visual hallucinations
Memory impairment
Parkinsonian signs
Neuroleptic sensitivity
Falls resulting from orthostatic hypotension
|
Memory impairment of Alzheimer’s disease but with some partial saving
Pronounced apraxia, visuospatial difficulties
Rapidly increasing quantifiable deficits in many cases
|
Particularly important are tests of visuospatial organization, such as constructional praxis tests (e.g., clock drawing, WAIS-IV Performance subtests, copy of the Rey-Osterrieth figure [Osterrieth 1944])
|
Vascular neurocognitive disorder
| ||
Variation of symptoms with subtype
Focality on examination
Abrupt onset
In multi-infarct neurocognitive disorder, stepwise progression
|
Language/memory retrieval difficulties common
Benefit from structural support/cueing
Asymmetric motor speed/dexterity
Executive inefficiencies
|
Particular attention to discrepancies on memory test (CVLT-II) between intact recognition and cued recall but impaired free recall
Trail Making Test, WAIS-IV Digit Span Backward
|
Parkinson’s disease neurocognitive disorder
| ||
Extrapyramidal motor disturbance
Gait dysfunction and frequent falls
Bradykinesia
Bradyphrenia
|
Slowed performance
Retrieval memory deficit
Executive deficiencies (slowed sequencing, impaired lexical fluency)
Impaired fine motor speed (asymmetry common)
Constructional deficits
|
Wisconsin Card Sorting Test
Trail Making Test, WAIS-IV Digit Span Backward, and animal and other verbal fluency tests
Benton Visual Retention Test or similar copy test; Judgment of Line Orientation Test
|
Huntington’s disease | ||
Early age at onset (midlife)
Choreiform movements
Neurocognitive disorder
Bradyphrenia
|
Slowed performance
Memory difficulty in retrieval
Benefit from retrieval supports (recognition OK)
Executive compromises
Poor verbal fluency/preserved naming
|
CVLT-II
Wisconsin Card Sorting Test, Trail Making Test, WAIS-IV Digit Span Backward, and animal and other verbal fluency tests
Motor testing; Finger Oscillation, Grooved Pegboard
|
Progressive supranuclear palsy | ||
Extrapyramidal syndrome but no tremor
Ophthalmic abnormalities (limited downgaze)
Axial rigidity
Pseudobulbar palsy
Frequent falls
|
Mild dysexecutive symptoms: impaired sequencing, fluency, flexibility
Motor slowing
Memory weakness characterized as inefficiencies in storage and retrieval
|
Wisconsin Card Sorting Test, Trail Making Test, WAIS-IV Digit Span Backward, and animal and other verbal fluency tests
Benton Visual Retention Test or similar copy test; Judgment of Line Orientation Test
|
Normal-pressure hydrocephalus | ||
Memory impairment
Gait disturbance
Incontinence
|
Slowed information processing
Memory retrieval problems
Benefit from retrieval supports
|
Special attention to CVLT-II (recall vs. recognition)
Naming and verbal fluency
|
Creutzfeldt-Jakob disease | ||
Typically, rapid onset and course
Neurocognitive disorder with pyramidal and extrapyramidal signs
Transient spikes on electroencephalogram
|
Rapidly evolving neurocognitive disorder
Subtypes with a profile akin to Alzheimer’s disease or a pronounced complex visuospatial disorder (Balint’s syndrome)
|
WAIS-IV processing speed and perceptual organization tasks
Judgment of Line Orientation Test
Constructional tasks
|
Neurocognitive disorder associated with geriatric depression | ||
Affective disorder
Psychomotor slowing
Memory complaints
Cognitive complaints linked temporally to the depressive disorder
|
Impaired performance on effortful processing tasks
Impaired attention, concentration, sequencing, cognitive flexibility, and executive control
Retrieval memory difficulty
Memory improvement with cueing/recognition
Behavioral tendencies to abandon tasks, poor motivation
|
Special attention to
CVLT-II (recall vs. recognition)
Naming and verbal fluency
Effort across all tests
|
Note. CVLT-II = California Verbal Learning Test, 2nd Edition; SD = standard deviation; WAIS-IV = Wechsler Adult Intelligence Scale, 4th Edition.
aAuthor citations are included in this table only for tests not listed in Table 6–1.
| ||
Alzheimer’s Disease
The presentation of AD neurocognitive disorder is dominated by a pronounced impairment in recent memory processing, which remains the most affected area of mentation in the majority of cases. This difficulty is now understood to arise from the selective involvement of the medial temporal lobe early in the illness (Braak and Braak 1991; Hyman et al. 1984), giving rise to impaired consolidation of newly learned information into more permanent memory stores located across interconnected neocortical structures. On formal neuropsychological testing, the memory problem of AD is manifest as a rapid forgetting of new information after very brief delays of 5 minutes or more (Welsh et al. 1991). Patients in the mild prodrome of the illness often show the characteristic memory disorder of more fully expressed disease and may show other mild deficits in executive function, language expression, visuoperception, and attention (Bäckman et al. 2005; Hayden et al. 2005; Twamley et al. 2006). At this early symptomatic stage, a diagnosis of mild cognitive impairment due to AD can be made (Albert et al. 2011). A diagnosis of mild cognitive impairment due to AD is synonymous with prodromal AD, a diagnostic label used in Europe (Dubois et al. 2010), and with DSM-5 mild neurocognitive disorder due to AD (American Psychiatric Association 2013).
As AD progresses, other areas of cognition become progressively more involved, reflecting the specific spread of neuropathological involvement to the lateral temporal areas, parietal cortex, and frontal neocortical areas (Small et al. 2000; Storandt et al. 2006; Welsh et al. 1992). With the advancement of symptomatic disease and as decline in independent function becomes apparent, a diagnosis of major neurocognitive disorder due to AD can be made (McKhann et al. 2011). At this stage, the prototypical changes appear in expressive language, visuospatial function, higher executive control, and semantic knowledge (Weintraub et al. 2012). At later stages of the illness, anomia with impaired semantic fluency (e.g., generation of names of animals) is generally seen on examination. Word search and circumlocution tendencies are common in conversational speech, whereas speech comprehension itself is better preserved, as are all other fundamental elements of communication (Weintraub et al. 2012). Visuospatial problems become more prominent in later stages of illness, resulting in dressing apraxia, difficulty in recognizing objects or people, and problems in performing familiar motor acts (Cronin-Golomb and Amick 2001). Subtle problems in spatial processing and visual motion detection can occur early and may be detectable only on formal examination (Mapstone et al. 2003). Visuospatial problems can be illuminated by tests of spatial judgment and visual organization (Rizzo et al. 2000). In everyday settings, visuospatial problems may manifest as intermittent topographical dis-orientation, leading to difficulties in finding familiar routes while driving (Rizzo et al. 1997). Figure 6–1 compares the memory loss characterizing AD and mild cognitive impairment with that characterizing normal aging.
Profiles of neuropsychological test performance by patients with mild cognitive impairment (MCI) and by patients with moderate Alzheimer’s disease (AD).
Bars indicate the performance of patients with MCI (n = 153) and moderately impaired AD patients (n = 277) on the subtests of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD; Tariot 1996) neuropsychological battery, compared with the performance of nonimpaired elderly control subjects (n = 158) of similar age, sex, and education. The overall neuropsychological test performance of the AD sample is well below that of both patients with MCI and subjects experiencing normal aging. Patients with MCI performed at normal levels on naming and praxis. Learning and verbal fluency were mildly affected in this group, falling at 71% of normal. Memory was particularly affected in both AD and MCI. Verbal recall on the CERAD Word List Memory test was 45% of normal in the MCI sample and only 28% for the AD patients. Visual memory was 51% of normal in MCI and 23% in AD.
Source. Data derived from the Cache County Study of Memory sample (K. A. Welsh-Bohmer, unpublished).
Cerebrovascular Disease
The neuropsychological profile of vascular dementia differs in many respects from that of AD, the largest difference being the absence of the profound memory impairment that is a hallmark of AD (Tierney et al. 2001). The presentation of vascular neurocognitive disorders will vary according to the type and extent of the vascular compromise—multiple infarctions, a single strategic stroke, microvascular disease, cerebral hypoperfusion, hemorrhage, or combinations of these etiologies (Cohen et al. 2002). Multi-infarct dementia, arising from multiple large- and small-vessel strokes, will demonstrate a pattern of multifocal impairments on testing that respect the cerebral territories involved by the infarctions (Chui et al. 1992; Román et al. 1993). In disorders attributed to diffuse small-vessel disease (e.g., Binswanger’s disease), the pattern shown on testing reflects the disruption in the dorsolateral prefrontal and subcortical circuitry (Kramer et al. 2002). Memory is involved, but the deficits are often patchy in nature. Patients may show impaired recollection of some recent event but show a surprising memory of some other occurrence transpiring within the same time frame. On formal neuropsychological testing, the pattern on memory testing is one of inefficient acquisition of new information leading to a flattened learning curve over repeating trials (Looi and Sachdev 1999; Padovani et al. 1995). Recall performance can be quite low, similar to that seen in AD and mild cognitive impairment, but rapid forgetting is not a typical feature (Hayden et al. 2005; Matsuda et al. 1998). The information acquired, albeit limited, is generally retained, so that savings scores between a final learning trial and a later delayed recall trial generally are high. Finally, recognition improves dramatically with a recognition format, suggesting a primary difficulty in retrieval rather than in storage or consolidation of new information (Hayden et al. 2005). Beyond memory, dysexecutive functions are typically involved, leading to slowed sequencing, cognitive inflexibility, and decreased verbal fluency (Mathias and Burke 2009). Asymmetries on sensory motor function or deficits in coordination also are frequently demonstrated.
Frontotemporal Lobar Degeneration
Frontotemporal lobar degeneration (FTLD) refers to a heterogeneous group of neurodegenerative conditions that are genetically, clinically, and neuropathologically diverse and represent collectively a major non-AD neurocognitive disorder. The onset of disease is typically in the presenium, distinguishing it from AD, in which the typical age at onset appears to occur later (i.e., after age 65). The exact prevalence of FTLD in late old age has not been conclusively established, but several studies suggest that it accounts for approximately 10%–20% of the early-onset major neurocognitive disorders (for a review, see Seltman and Matthews 2012). The neuropathological features of FTLD are heterogeneous, but uniformly the histological changes and atrophy are confined to the frontal and anterior temporal cortices.
Clinically, from the outset, the neuropsychological profile of FTLD is distinct from that of AD or any other form of major neurocognitive disorder (Weintraub et al. 2012). There are typically prominent early changes in behavior, personality, or language as opposed to impairments in memory and other aspects of cognition. As a consequence of impaired judgment and social inappropriateness, patients with FTLD may have tremendous difficulties in their everyday lives, but on formal psychometric screening they may score entirely within normal limits. A number of investigations have delineated the cognitive profile of these disorders (Pachana et al. 1996) and indicate double dissociations between FTLD and AD. Specifically, in AD, there is classic rapid forgetting; in FTLD, there is impairment in executive function. The dysexecutive syndrome of FTLD is characterized by slowed information processing, cognitive rigidity, diminished abstract reasoning, poor response inhibition, and impaired planning. At the neurobehavioral level, there are major changes in personality and general social decorum. Disinhibition or its converse, behavioral apathy and inertia, frequently occurs. Insight into impairment and into personality change is also affected, and this capacity commonly is disturbed early in the course of FTLD (Rankin et al. 2005). This behavior pattern contrasts with that of AD, in which insight is generally lost later in the neurodegenerative process (Salmon et al. 2008). In fact, appreciation of memory impairment and other symptoms may be quite acute early in the disease and be a harbinger of the progressive disorder (Geerlings et al. 1999). In instances of FTLD aphasia, the profile may be distinguished from similar vascular disorders with aphasia based on a history of insidious onset and indolent change. Imaging is often necessary to rule out stroke and to visualize focal brain atrophy.
There is considerable clinical variability in the presentation of FTLD, and at least three different subtypes of FTLD are now described based on common clinical and neuropsychological features (Seltman and Matthews 2012; Warren et al. 2013): 1) a so-called behavioral variant, 2) semantic dementia, and 3) progressive nonfluent aphasia. FTLD can also be segregated into two subtypes based on regional brain involvement of predominantly the frontal or temporal neocortices (e.g., Seeley et al. 2005). Otherwise, the neuropathological features of FTLD appear heterogeneous (Brun et al. 1994; Cairns et al. 2007; Jackson and Lowe 1996). Microvacuolation, neuronal loss, cortical thinning, and gliosis are often observed on gross and histological examination. Three major pathogenic proteins are implicated in FTLD: phosphorylated tau, transactive response DNA-binding protein 43 (TDP-43), and fused in sarcoma protein (FUS). With immunohistochemistry, some cases show the spherical Pick bodies with tau-positive inclusions. However, the majority of cases stain positive for ubiquitin (TDP-43), not tau, and invariably are without these Pick bodies. Clinicopathological studies that are beginning to emerge suggest that the clinical expression of some forms of FTLD may be related to the molecular pathology. Some forms of progressive aphasia have demonstrated a relationship to the tauopathies (Cairns et al. 2007), semantic dementia to TDP-43–associated pathology, and some behavioral variants of FTLD to FUS-associated pathology (Warren et al. 2013). Work continues in this area, having implications for efforts to identify biomarkers that would help distinguish the early clinical expression of FTLD from primary psychiatric and other neurological disorders.
It should be underscored that the subtypes do not always present distinctly and that there can be a combination of symptoms. Additionally, there are other types of frontal lobe disorders, which can include early-onset neurocognitive disorder associated with motor neuron disease, such as amyotrophic lateral sclerosis with dementia. There are also various degenerative conditions with secondary frontal lobe effects. Vascular conditions such as subcortical ischemic vascular dementia or Binswanger’s disease (see the earlier “Cerebrovascular Disease” section) often present with frontal lobe impairments, which are likely secondary to the disruption of subcortical white matter pathways.
Parkinson’s Disease and Lewy Body Disease
Patients with Parkinson’s disease commonly have cognitive complaints, and many go on to develop a major neurocognitive disorder. Although the cumulative prevalence estimates of Parkinson’s disease dementia (PDD) remain unclear, some estimates suggest that 10%–30% of patients newly diagnosed with Parkinson’s disease develop functional impairment within 3 years (Reid et al. 1996; Williams-Gray et al. 2007). Related to PDD is dementia with Lewy bodies (DLB), a progressive neurological condition that is heralded by cognitive, behavioral, and functional impairments, as opposed to extrapyramidal motor symptoms, and is associated with a disorder of α-synuclein metabolism. The disorder has been referred to by a variety of names—diffuse Lewy body dementia, senile dementia of the Lewy body type, and the Lewy body variant of AD—depending in large measure on what the regional distribution of the neuropathology is and whether amyloid plaques co-occur (McKeith et al. 2005; Zaccai et al. 2005). The recognition that DLB and PDD share a common biology has led to their being grouped together and referred to collectively as Lewy body dementias (LBDs) (Lippa et al. 2007).
Clinically, PDD and DLB present differently, but they share a core symptom complex that allows their recognition and distinction from AD (Geser et al. 2005). In PDD, the prevailing features are parkinsonism, akinetic rigidity, and generalized slowing in motor movement/initiation and thought processes (bradykinesia and bradyphrenia, respectively). DLB, in contrast, is characterized by early fluctuations in cognition and attention, recurrent and persistent visual hallucinations, and extrapyramidal motor symptoms. Diagnosing the conditions rests on the relative occurrence of dementia with respect to the extrapyramidal motor symptoms. In PDD the symptoms of dementia emerge in the context of a previously established diagnosis of Parkinson’s disease, whereas in DLB the symptoms of cognitive and functional impairments either predate or follow the onset of parkinsonian symptoms within a 1-year time interval.
On neuropsychological evaluation, the cognitive impairments of PDD and DLB are similar, but the profiles can be differentiated from those typically observed in AD (Tröster 2008; Welsh-Bohmer and Warren 2006). Both PDD and DLB are characterized by a pattern of memory retrieval problems and mild dysexecutive disturbances, which early in the course are less dramatic and globally impairing than the cognitive deficits of AD (Hamilton et al. 2004). Visuospatial disturbances are commonly observed early in the course of the LBDs (Ballard et al. 1999; Hanson et al. 1990; Salmon et al. 1996), but expressive language such as naming tends to be better preserved than in AD (Ballard et al. 1999; Heyman et al. 1999). Despite these differences on neuropsychological testing, making a solid differential diagnosis based solely on the cognitive profile alone will be difficult (Monza et al. 1998; Soliveri et al. 2000; Testa et al. 2001), particularly in the very early stages. The integration of the clinical examination findings (which includes history and review of systems, motor examination, cognitive findings, behavioral ratings, psychiatric interview, and supportive laboratory studies such as neuroimaging) is necessary to clarify these disorders from one another and to make an accurate diagnosis early in the process (Litvan et al. 2012). In this context, particular attention to the history of symptoms (e.g., fluctuations in ability throughout the day) and to the presence or absence of defined behavioral impairments is crucial to the diagnosis (Geser et al. 2005; Pillon et al. 1991). Cognitively impaired patients with Parkinson’s disease can be differentiated from patients with AD by the comparatively increased apathy observed in the former group and memory impairment within the latter (Cahn-Weiner et al. 2002), whereas presence of visual hallucinations not associated with treatment can help distinguish LBD from PDD (Aarsland et al. 2001). Visual hallucinations can occur in AD but are uncommon in the earliest stages; hence, their presence in a neurocognitive process signals another etiological cause such as LBD.
Geriatric Depression and Neurocognitive Disorders
Two of the most common uses of neuropsychological assessment for elderly patients are evaluating memory disorders and determining the role of depression. By itself, serious depression in elderly people can result in disabling cognitive impairment, or what has been called dementia of depression or pseudodementia (see Breitner and Welsh 1995). The problem of geriatric depression is fairly common, with some epidemiologically based studies suggesting that nearly one-third (28%) of elderly individuals older than 65 years exhibit prominent affective syndromes (Lyketsos et al. 2001). Depression also frequently co-occurs in the context of a range of medical disorders, including AD, stroke and cerebrovascular conditions, and Parkinson’s disease, complicating the diagnosis of these disorders and exacerbating functional loss associated with each (Diniz et al. 2013; Krishnan 2000; Migliorelli et al. 1995; Reichman and Coyne 1995). Distinguishing between depression and other conditions in elderly people can be challenging but is assisted by a thorough screening of both depressive symptoms and cognitive status.
When screening fails to give a clear picture of the contribution of depression to the cognitive picture, neuropsychological examination can assist. It must be noted that depression in late life is clinically heterogeneous, with variable concordance between severity of depressive symptoms and level of cognitive impairment (Alexopoulos et al. 2002; Butters et al. 2008). Despite the heterogeneity, there are some distinctive neurocognitive and behavioral changes that appear ascribable to the condition of late-life depression and that are characteristic of a rather large subgroup of patients who present without neurological disease (Beats et al. 1996; Lockwood et al. 2002). The neurocognitive profile tends to be one of a dysexecutive syndrome with impairments in planning, organization, initiation, sequencing, working memory, and behavioral shifting in response to feedback. Short-term memory and visuospatial skills are also disturbed, in part because of the attentional and organizational compromises. Behaviorally, these patients show apathy and psychomotor retardation as opposed to prominent mood dysphoria of younger counterparts.
On formal neuropsychological testing, these patients show impairments on tests sensitive to frontal lobe function. Difficulties can be readily seen on tests of selective and sustained attention, verbal fluency, inhibitory control, and set shifting (Boone et al. 1994, 1995; Lockwood et al. 2002). Memory is impaired on both acquisition and recall, leading to a profile characterized by a flattened learning curve and impaired free recall of previously learned information after brief delays (Hart et al. 1987). Recognition memory is better preserved but can be characterized by false-negative tendencies (not recognizing previous target material). The memory disturbance of depression is distinguished from AD by the impaired acquisition and recognition elements. In AD, acquisition is relatively better preserved, whereas recognition is characterized by false-positive tendencies (recognizing foils incorrectly as previously presented targets). The profile of impairment in depression leads to the impression of generalized cognitive inefficiency and suppression of performance. Other qualitative differences also may be seen in the performance of these two groups; in depressed patients there is often a heightened tendency to abandon effortful tests.
Importantly, even with treatment, not all of the cognitive impairments associated with geriatric depression remit (Butters et al. 2000). In the older patient, this may be due to the co-occurrence of another disease process, such as AD or cerebrovascular disease (Butters et al. 2008). Although far from conclusive, a number of studies report that depression in elderly people exerts a discernible additional effect on cognition and functional independence and may be a risk factor for later cognitive decline (Steffens et al. 2006). Neuropsychological evaluation of elderly patients can provide clinically useful information regarding the nature of the cognitive failures, differential diagnostic information, and a baseline for future comparisons. The information is useful in diagnosis and management, regardless of whether all of the cognitive change detected is reversible.
Conclusion
The neuropsychological evaluation provides a useful and cost-effective management approach for diagnosis and management of the growing geriatric population with memory complaints. A neuropsychological evaluation is not needed in most major neurocognitive disorders in which symptoms are obvious and the diagnosis is secure. It can be enormously useful, however, in more complex, less straightforward diagnostic situations, such as in early AD detection or in geriatric depression. By its objective nature, the neuropsychological examination has strong applications in medical management, providing information regarding patient capacities and deficits that is important for choosing intervention approaches and for guiding future decision making with respect to competency and safety.
Key Points
- The neuropsychological presentation of Alzheimer’s disease is characterized by a pronounced deficit in the consolidation of new information from short-term, immediate memory to a more permanent store. Thus, the deficit early in the disorder is a problem of rapid forgetting of newly learned information.
- The profile of normal cognitive aging is characterized by modest declines on executive function tests, in large measure because of inefficiencies in multitask processing and declines in perceptual motor speed.
- Frontotemporal lobar degeneration is characterized by profound functional and behavioral changes. The neurocognitive deficits associated with the disorder, particularly in the early stages, may be difficult to discern with mental status instruments. Neuropsychological testing targeting executive functions can tease out the impairments in behavioral regulation, disinhibition, perseveration, judgment, and abstraction.
- The neuropsychological deficits associated with neurocognitive disorder due to Parkinson’s disease are clinically very similar to those of a closely aligned condition, neurocognitive disorder with Lewy bodies. However, the neuropsychological profiles of these conditions can be distinguished from that of neurocognitive disorder due to Alzheimer’s disease. Visuospatial deficits are common early in neurocognitive disorder due Parkinson’s disease and neurocognitive disorder with Lewy bodies, and the memory disorders are less severe than those of Alzheimer’s disease.
- Geriatric depression can cause significant impairments in the efficiency of cognitive processing, leading to selective problems in sustained attention, concentration, and memory. It is a risk factor for cognitive decline to dementia. When co-occurring with progressive neurological disorders, such as Alzheimer’s disease or vascular neurocognitive disorder, depression can lead to excess disability and an overall reduction in the quality of life that might otherwise be achieved.
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