Dementia with Lewy bodies (DLB) is the second leading cause of cognitive impairment among the elderly. While it is usually accompanied by the neocortical neuritic plaques (NP) and entorhinal neurofibrillary tangles (NFT) characteristic of Alzheimer disease (AD), and so can be construed 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. Among DLB cases, neocortical Lewy body (LB) counts, modified Braak stages 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 reactivity were uncorrelated with DLB dementia. Despite comparable LB counts and ChAT losses, the DLBD were significantly less demented than the LBV patients. We conclude that neocortical LB and ChAT depletion contribute to cognitive impairment in DLB and that concomitant AD pathology in LBV, represented by higher Braak stages and NP, promotes increased dementia severity compared with that encountered in DLBD.

Author notes

Sources of support: This research was supported by a Physician Scientist award to WS from the National Institutes of Health (NIH) grant AG000353 and by a Special Fellowship in Neurosciences and Traumatic Brain Injury from the VA Central Office. Additional support was provided by NIH grants AG 12963, AG08201, AG08205, AG05131, and AG 10689, and by a contract from the State of California Alzheimer's Disease Diagnostic and Treatment Centers.