Patterns of cognitive impairment in Alzheimer's disease: assessment and differential diagnosis

In routine clinical practice, the diagnosis of Alzheimer's disease (AD) is commonly made according to NINCDS-ADRDA criteria. As pathological verification is typically not available, such a diagnosis remains probable rather than definite. A diagnosis of probable AD is nevertheless fairly accurate (0.75-0.96), and may serve as a surrogate gold standard in clinical studies. Probable AD is often considered a diagnosis of exclusion, but AD neuropathology characteristically evolves in an ordered topographic sequence, which is mirrored in the pattern of evolution of neuropsychological deficits. Recognition of the resulting temporal profile of cognitive domain involvement allows positive rather than merely exclusionary diagnosis. Certain other dementias may be difficult to distinguish from AD clinically: notably frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and various subtypes of vascular cognitive impairment. The distinction is made more difficult by the existence of variants of AD, presenting with predominant impairment of executive, visuoperceptual, or language domains, as well as by the common occurrence of mixed pathologies. Against this background, the neuropsychological features of AD and its variant presentations, and its distinction from other dementias are reviewed. The properties of commonly-used cognitive assessment tools (MMSE, Mattis DRS, ADAS-Cog, CERAD and CAMDEX-R) are discussed, and the issue of diagnosing incipient AD on clinical grounds before the NINCDS-ADRDA criteria are fulfilled is addressed.