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Living with Dementia

Cognition and Cognitive Testing

  • - Normal Aging & Dementia
  • Jun 25, 2011
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Tags: | alzheimer type | american academy of neurology | cognition | cognitive dysfunction |

As noted above, the diagnoses of mild cognitive impairment and dementia of the Alzheimer type both require the presence of memory impairment. To distinguish between MCI and DAT, it is important to determine the degree and course of memory impairment, the presence or absence of additional domains of cognitive dysfunction, and the impact of cognitive problems on the individual’s daily functioning (Petersen et al. 1997, 1999; Collie and Maruff 2000; Petersen 2000).

The report of the Quality Standards Subcommittee of the American Academy of Neurology (Knopman et al. 2001) describes methods of assessing cognition for the evaluation of dementia. The subcommittee recommended the use of both screening instruments and neuropsychological evaluations in the diagnostic process. In general, brief screening tests, such as the Mini-Mental State Examination (MMSE; Folstein, Folstein, and McHugh 1975) or the Dementia Rating Scale (Mattis 1988), which assess multiple cognitive domains, have reasonable sensitivity and specificity for the early stages of DAT (Butters, Salmon, and Butters 1994). Some screening tests have a relatively wide range of item difficulty levels and can therefore also be used to track cognitive changes over the years (Butters, Salmon, and Butters 1994). However, very brief measures such as the MMSE have limited sensitivity and range, especially for individuals with a high baseline level of functioning.

Neuropsychological evaluations are highly accurate at discriminating dementia of the Alzheimer type from normal aging (Becker et al. 1994). A comprehensive neuropsychological evaluation of a person with dementia or suspected dementia includes a clinical interview and history of the presenting cognitive problem and related background medical and demographic information. Interview of a reliable informant is an important part of the comprehensive evaluation. A number of cognitive domains are assessed as a standard part of a neuropsychological assessment; those most frequently found to be impaired in persons with DAT are described briefly below. As noted above, in both DAT and MCI, the core deficit is memory impairment out of proportion to that seen in healthy older adults. To distinguish between MCI and mild DAT, examination of other cognitive domains and functional status is crucial.

Memory Impairment

The initial presenting symptom of dementia of the Alzheimer type is usually insidiously progressive memory impairment (Morris 1996; Troster 1998). The memory impairment exhibited in DAT has been the focus of substantial research, as it is the most distinguishing feature of the disease. Specific components of memory (see definitions below) are differentially affected as a function of the stage of DAT.  Episodic and semantic memory were originally distinguished by Tulving and Donaldson (1972),  and both are impaired early in DAT, with episodic memory perhaps showing the earliest changes. In contrast, other components such as procedural memory may remain relatively unaffected until later in the disease (e.g.,  Kaszniak 1986;  Poon et al.  1986;  Shimamura 1989, 1990; Birren and Schaie 1990; Carlesimo and Oscar-Berman 1992).

Episodic Memory
Episodic memory refers to the ability to learn and remember new contextual information. In MCI and DAT, episodic memory is often affected, and can be characterized by failure of consolidation and rapid forgetting. This can be assessed using measures of new verbal and nonverbal learning, for example, learning a list of words (California Verbal Learning Test; Delis et al. 1987) or recalling short stories or geometric designs (Wechsler Memory Scale; Wechsler 1987). Measures of delayed recall and forgetting are highly discriminative for persons with DAT and normal controls, but less discriminative for mild DAT and moderate DAT (Welsh et al. 1991, 1992; Becker, Lopez, and Butters 1996; Gray and Della Sala 1996; Gabrieli 1998).

Semantic Memory and Language
Semantic memory is defined as long-term memory for culturally shared general knowledge about words, concepts and symbols, their associations, and rules for their manipulation (Butters et al. 1987; Farah et al. 1997). It is increasingly apparent that persons with DAT also show deficits in semantic memory. Semantic memory is affected early in the disease course in the majority of cases (Hodges and Patterson 1995).  This feature was listed by Alois Alzheimer in 1907 as part of the core cluster of symptoms of DAT. Relevant contemporary studies indicate naming deficits or semantic errors such as word substitutions on picture naming tasks in persons with DAT (Hodges, Salmon, and Butters 1991). Measures of word generation can also be used to assess semantic memory. Persons with DAT perform more poorly when asked to generate words belonging to a particular category than when asked to generate words beginning with a particular letter (Butters et al. 1987; Salmon, Heindel, and Lange 1999); while this is not a pure language measure (e.g., it also assesses the ability to initiate and to retrieve words, which can be considered executive functions), the distinction between poorer ability to generate categorical knowledge versus general word knowledge also supports the notion of a breakdown of, or inability to access, the network of semantic knowledge and meaningful associations (Chertkow and Bubb 1990).  Johnson and Hermann (1995)  and Saykin et al. (1999) reported deficits in persons with early DAT on category exemplar decision-making tasks such as recognizing that “vehicle-bus” match while “vehiclecarrot” do not.

Attention and Working Memory
Basic attentional capacity is generally spared in dementia of the Alzheimer type until later stages. More complex forms of attention, such as the ability to sustain or direct attention, are impaired earlier in DAT. Recently, impairment of working memory has also been identified as an early problem in DAT (Lange et al. 1995; Belleville, Peretz, and Malenfant 1996; Collette et al. 1997). Working memory refers to the ability to hold information in mind, or “on-line,” while retrieving or processing other relevant information (Baddeley 1986; Baddeley and Hitch 1994). Impairment in this domain may also contribute to the deficits found in a variety of other cognitive functions, such as speed of information processing and semantic and episodic memory,  since attention and working memory are important for encoding,  consolidation,  and retrieval (Craik and Kester 2000).

Executive Ability

Executive ability refers broadly to a set of behaviors that enable people to engage in goal-directed activities.  They include organization and sequencing, planning, mental flexibility, judgment, and abstract reasoning. Many neuropsychological tests of executive abilities tap more than one of these skills. Some of these measures, such as the Wisconsin Card Sorting Test (Heaton et al. 1993), are more complex and are appropriate for assessing subtle changes in MCI or mild DAT. Others assess more basic executive functions and are suitable for the middle stage of the disease. For example, basic measures of judgment such as that included in the Neurobehavioral Cognitive Status Examination (Schwamm et al. 1987) examine the ability to solve everyday problems.

Visuospatial/Constructional and Visuoperceptual Abilities

Visuoperceptual and spatial abilities affect important practical functions, such as recognizing faces or finding one’s way around a store or neighborhood.

Constructional deficits are evident in drawing,  copying,  and reproduction of simple figures or designs.  Neuropsychological tests of these abilities are frequently timed. Because of the documented slowing of speed of processing with age (Spirduso and MacRae 1990), older participants often perform more poorly than younger subjects on such measures. In individuals with DAT, there are changes in the actual understanding of spatial relations and three-dimensional perception. As the disease progresses, even simple two-dimensional copying or figure matching can become impaired (Moss and Albert 1988).

Praxis

Praxis refers to the ability to carry out skilled intentional movements and can affect everyday functions such as dressing. Apraxia can be tested through observation of single and sequential movements of the mouth, hand, and body.

Apraxia typically manifests in middle to later stages of DAT, when the memory and other higher-level cognitive deficits are already apparent.

Other

Tests of instrumental activities of daily living skills are often helpful in differential diagnosis, and deficits have been related to brain structure and function (Souder, Saykin, and Alavi 1995). Further, measures of depression (e.g., Geriatric Depression Scale or Beck Depression Inventory)  and vascular involvement (Hachinski 1990) are likely to help with differential diagnosis.

In summary, as noted above, many screening instruments are available for the initial assessment of cognitive impairment associated with mild cognitive impairment and early dementia of the Alzheimer type that clinicians can use in their office. Among the most commonly used are the Mental Status Questionnaire (Kahn et al.  1960),  the Memory-Information-Concentration Test (Blessed, Tomlinson, and Roth 1968), the Short Portable Mental Status Questionnaire (Fillenbaum, Landerman, and Simonsick 1998; Pfeiffer 1975), and the MMSE (Folstein, Folstein, and McHugh 1975). Even when individuals perform normally on these tests, comprehensive neuropsychological evaluation may be indicated to rule out more subtle cognitive changes, especially in those persons with subjective and informant-endorsed complaints,  and in those individuals with presumed very high premorbid (or baseline) intelligence.

Neuroanatomy

The mean brain weight of normal young adult males varies from approximately 1300 to 1380 grams (Duckett 1991). With normal aging, the average brain weighs 7 - 8% less than the average brain of a middle-aged adult (Tomlinson 1977; Lauter 1985); however, there is considerable variability among individuals that may be due to the fact that “normal” study populations are not always rigorously screened for medical conditions that might also impact on the brain. Normal aging is associated with subtle changes in brain structure, including generally mild cortical atrophy and ventricular enlargement. Regionspecific studies show greater neuronal decreases in some areas, including the superior frontal and temporal gyrus, precentral gyrus, visual cortex, locus ceruleus, substantia nigra, basal nucleus of Meynert, and cerebellar Purkinje cells (Lauter 1985).

In primary degenerative dementia, the decrease in brain weight is as much as 10% more than that seen in normal aging (Terry and Davies 1983). As in normal aging, atrophy and eventual cell loss is region-specific in DAT. Brains from persons with DAT demonstrate greater neuronal loss in frontal and temporal regions (Mountjoy et al.  1983).  Subcortical nuclei including the locus ceruleus and basal nucleus of Meynert also show greater cell loss in DAT, but this may be more typical in those with a younger age of onset (Iversen 1987).

The dominant theory of DAT has been related to loss of cholinergic cells, but recent findings of upregulation of choline acetyltransferase activity in MCI and mild DAT may extend this model to include compensatory changes (DeKosky et al.  2002).  The pathology of DAT includes neurofibrillary tangles,  senile plaques,  and synaptic loss,  as well as more pronounced cortical atrophy ap
pearing as sulcal and ventricular enlargement disproportionate to age. Structural brain changes have been reported not only early in the disease, but also in persons with MCI. Medial temporal structures, including the hippocampus and entorhinal cortex, are particularly vulnerable in the earliest stages of DAT.

###

Laura A. Flashman, Ph.D.,
Heather A. Wishart, Ph.D.,
Thomas E. Oxman, M.D.,
and Andrew J. Saykin, Psy.D.

###

REFERENCES

  1. Kral, V.A. 1958. Neuro-psychiatric observations in an old peoples home. Journal of Gerontology 13:169-76.
  2. Kral, V.A. 1962. Senescent forgetfulness: Benign and malignant. Canadian Medical Association Journal 86:257-60.
  3. Krasuski, J.S., G.E. Alexander, B. Horwitz, et al. 1998. Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biological Psychiatry 43 (1):60-68.
  4. Kuhl, D.E., R.A. Koeppe, S. Minoshima, et al. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 52:691-99.
  5. Laakso, M.P., H. Soininen, K. Partanen, et al. 1995. Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions. Journal of Neural Transmission, Parkinson Disease and Dementia Section 9 (1):73-86.
  6. Lange, K.W., B.J. Sahakian, N.P. Quinn, et al. 1995. Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia. Journal of Neurology, Neurosurgery, and Psychiatry 58 (5):598-606.
  7. Lauter, H. 1985. What do we know about Alzheimer's disease today? Danish Medical Bulletin 32 (Suppl. 1):S1-21.

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