The prevalence of Lewy body pathology across nine international community-based cohorts

Achoimre

Abstract Reported prevalence estimates of Lewy body pathology (LBP) vary widely, often without considering brain regional distributions or demographic influences. Large, population-representative autopsy cohorts are needed to provide estimates and clarify the distribution and clinical implications of LBP. Neuropathological, genetic and clinical data were pooled from nine community- or population-based brain autopsy cohorts in the USA (n = 6), Brazil, Austria and Finland (n = 7309 total; 59% women; mean age of death 84.2 years). Cognitive status was available for 6166 participants: dementia (38.5%), mild cognitive impairment (14.8%) and cognitively unimpaired (47.0%). Frequency of LBP was examined by anatomical distribution (neocortical, limbic, brainstem, amygdala, olfactory) and stratified by covariates. Prevalence was calculated in meta-analysis, and mixed-effect logistic regression examined associations with sex, cognitive status, Alzheimer’s disease neuropathological change (ADNC) and limbic-predominant age-related transactive response DNA-binding protein (TDP)-43 encephalopathy neuropathologic change (LATE-NC) co-pathology. Overall, 27.3% of participants had LBP: neocortical 8.4%, limbic 6.8%, brainstem 4.8%, amygdala 3.7% and olfactory 3.6%. Neocortical LBP was associated with dementia [present in 15%; odds ratio (OR) = 4.06 (95% confidience interval (CI) 3.24–5.10)] and with increased odds of ADNC [OR = 2.30 (95% CI 1.88–2.81)] and LATE-NC [OR = 2.03 (95% CI 1.69–2.44)]. Sex differences were not observed in the frequencies of neocortical or limbic LBP. However, amygdala-predominant LBP was more frequent in women [OR = 1.53 (95% CI 1.06–2.21)] whereas brainstem-predominant LBP was more common in men [OR = 0.64 (95% CI 0.49–0.84)]. Additionally, amygdala-predominant LBP was associated with increased odds of comorbid ADNC [OR = 12.7 (95% CI 5.30–30.6)] while brainstem-predominant LBP was not associated with greater odds of ADNC co-pathology [OR = 0.88 (95% CI 0.67–1.16)]. Pooling data from large, international community-based autopsy cohorts allows for more robust estimates of region-specific LBP prevalence and their associations with cognitive status. The observed sex- and co-pathology-specific differences in brainstem and amygdala-predominant LBP highlight potential biological heterogeneity and suggest that distinct disease pathways may underlie these patterns.