The neuropathology of older persons with and without dementia from community versus clinic cohorts

Abstract

Community-based cohorts of older persons may differ neuropathologically from clinic-based cohorts. This study investigated age-related pathologies in persons with and without dementia and included autopsied participants from two community-based cohorts, the Rush Religious Orders Study (n=386) and the Memory and Aging Project (n=195), and one clinic-based cohort, the Clinical Core of the Rush Alzheimer's Disease Center (n=392). Final clinical diagnoses included no cognitive impairment (n=202), mild cognitive impairment (MCI) (n=150), probable Alzheimer's disease (AD) (n=474), possible AD (n=88), and other dementias (n=59). Postmortem diagnoses included pathologic AD, cerebral infarcts, and Lewy body disease. Community-based persons with clinical AD had less severe AD pathology (p<0.001) and had more cerebral infarcts (p<0.001) compared to clinic-based persons. Additionally, community-based persons with MCI had more infarcts compared to clinic-based persons. Overall, there was a higher proportion of Lewy bodies and atypical pathologies in the clinic-based compared to the community-based cohorts (p<0.001). Community-based persons with probable AD show less severe AD pathology and more often have infarcts and mixed pathologies; those with MCI more often have infarcts and mixed pathologies. Overall, clinic-based persons have more Lewy bodies and atypical pathologies. The spectrum of pathologies underlying cognitive impairment in clinic-based cohorts differs from community-based cohorts.

Fig. 1

Distribution of neuropathology in persons from community studies (A) compared to clinical cohort (B) with and without dementia. Clinical diagnoses: NCI (no cognitive impairment); MCI (mild cognitive impairment); prob AD (probable Alzheimer’s disease), poss AD (possible Alzheimer’s disease); other dementias (includes non-AD dementias, see text). Pathologic diagnoses: AD (Alzheimer’s disease; black bar = High likelihood NIA-Reagan; diagonal lines = intermediate likelihood NIA-Reagan); Inf (Cerebral infarcts; black bar = macroscopic infarcts; diagonal lines = microscopic infarcts only); LB (Lewy bodies; black bar = neocortical Lewy bodies; diagonal lines = nigral or limbic Lewy bodies only); FTLD (frontotemporal lobar degeneration or other atypical pathologies). See text for further information regarding clinical and neuropathologic diagnoses.