Differential diagnosis of dementing diseases

Abstract

Evaluation of the cognitively impaired patient necessitates documentation of dementia, with the help of standard and robust neuropsychological tests, followed by identification of focal, multifocal, or subcortical neurological signs which help differentiate the most common dementing diseases. The usual diagnostic dilemma is to distinguish Alzheimer’s disease from circulatory dementia. Until recently, Alzheimer’s disease was considered a diagnosis of exclusion, with confirmation only by pathological examination. Invasive tests, such as lumbar puncture for protein markers or skin biopsy for genetic markers, may aid in the antemortem diagnosis of Alzheimer’s. Noninvasively determined information which may provide diagnostic clues includes family history of dementia and fingerprint patterns. Circulatory dementia need not be confined to multi-infarct dementia, but may also include dementia accompanying cerebrovascular or cardiovascular disease. Features associated with circulatory dementia include remote history of urinary and gait disturbances, ear hair growth, and “infarcts” on MRI and CTT. Although the significance of “infarcts” on MRI is unclear, they are associated with high Hachinski ischemic score, hypertension, and cardiac arrhythmias. “Infarcts” on MRI are more sensitive, but less specific, than “infarcts” on CTT, in diagnosing circulatory dementia. Techniques of decision analysis can help determine the diagnostic utility of the Hachinski score and its components, as well as of imaging techniques and other diagnostic aids, in differential diagnosis. In drug trials for Alzheimer’s, where maximum sensitivity in the diagnosis of circulatory dementia is needed to exclude inappropriate subjects, the MRI is the imaging procedure of choice. Conversely, drug trials for circulatory dementia should use the CTT to enhance specificity. In the absence of specific therapeutic intervention, either procedure may be used, as overall diagnostic utility of the CTT and MRI, as determined by the Brier score, is comparable.