Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study

Abstract

This report summarizes findings from 443 autopsies on Japanese-American men followed as active participants in the Honolulu-Asia Aging Study from 1991 through 2003. Five distinct neuropathological lesion types were found to have strong, partially, or completely independent associations with cognitive impairment and/or dementia in the final years of life. They were: Alzheimer lesions (neocortical neurofibrillary tangles and neuritic plaques), microvascular infarcts (microinfarcts and lacunar infarcts), neocortical Lewy bodies, hippocampal sclerosis, and generalized brain atrophy. Atrophy was strongly associated with both Alzheimer lesions and microvascular infarcts, but was also observed in decedents with negligible levels of these and the other lesions. About half of the hippocampal sclerosis cases appeared to be linked to Alzheimer lesions. A weak association of hippocampal sclerosis with microvascular infarcts was also noted. Comparable 3-level indices were defined for each of the five lesion types to facilitate comparisons of associations with cognitive impairment and dementia. Multiple combinations of the five lesion types were observed. The development of dementia in the final years of life was more closely correlated with their combined numbers and severities than with specific lesion types. In this autopsy panel, microvascular infarcts were identified as the sole or dominant lesion in 33.8% of the demented or definitely impaired decedents, compared with Alzheimer lesions in 18.6% and co-dominant lesions (most often Alzheimer and microvascular) in 14.2%. These or one or more of the other lesion types were observed in 87.9% of the demented or definitely impaired decedents.