The neuropsychological profile of Alzheimer disease

Abstract

Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.

Figure 1.

The neuropsychological profiles of dementia reflect the impact of disease on distinctive neuroanatomic networks associated with complex cognitive domains. For example, prominent amnesia is associated with medial temporal dysfunction, whereas aphasia is a consequence of left perisylvian dysfunction. The relationship between clinical symptoms and underlying neuropathology, however, is less straightforward, as indicated by the multiple neuropathologic diagnoses associated with the various clinical dementia syndromes. The thickness of the lines connecting the clinical and neuropathologic levels represents the strength of associations between them (Mesulam 2000).

Figure 2.

Three graphs, each schematically representing early- and late-stage cognitive/behavioral profiles of three neuropsychologically distinct dementia syndromes. The height of the bars represents the level of impairment: mild, moderate, or severe. In late stages of any dementia syndrome (represented by gray bars) cognitive functions are similarly impaired in an undifferentiated manner and it is difficult to pinpoint one single domain that characterizes the syndrome. However, in early stages, represented by black bars, it is possible to differentiate among domains that are unimpaired or mildly impaired and those that are distinctly abnormal. The most typical early cognitive profile of dementia of the Alzheimer type is one of a prominent amnesia with additional cognitive deficits (“plus”; top graph); in primary progressive aphasia, the early stages are marked by salient language deficits in relative isolation (middle graph); in behavioral variant frontotemporal dementia, the most salient findings in early stages are in the domains of comportment and executive functions (bottom graph).