DEMENTIA WITH LEWY BODIES VERSUS PURE ALZHEIMER-DISEASE - DIFFERENCESIN COGNITION, NEUROPATHOLOGY, CHOLINERGIC DYSFUNCTION, AND SYNAPSE DENSITY

Dementia with Lewy bodies (DLB) is the second leading cause of cogniti ve impairment among the elderly. While it is usually accompanied by th e neocortical neuritic plaques (NP) and entorhinal neurofibrillary tan gles (NFT) characteristic of Alzheimer disease (AD), and so can be con strued as a Lewy body variant of AD (LBV), it also occurs in pure form as diffuse Lewy body disease (DLBD). We assessed cognitive status in 17 DLB patients (12 with LBV and 5 with DLBD) and compared the results with 12 AD subjects and 5 controls. We then sought to determine which neuropathologic abnormalities correlated with cognitive impairment. A mong DLB cases, neocortical Lewy body (LB) counts, modified Braak stag es of NFT burden in the entorhinal cortex, neocortical NP counts, and loss of choline acetyltransferase (ChAT) activity all correlated with dementia severity. Unlike AD, neocortical NFT and anti-synaptophysin r eactivity were uncorrelated with DLB dementia. Despite comparable LB c ounts and ChAT losses, the DLBD were significantly less demented than the LBV patients. We conclude that neocortical LB and ChAT depletion c ontribute to cognitive impairment in DLB and that concomitant AD patho logy in LBV, represented by higher Braak stages and NP, promotes incre ased dementia severity compared with that encountered in DLBD.