The goal of this study was to examine the association of cerebrovascular disease with clinical presentation and progression of Lewy body dementia (LBD). Using the National Alzheimer’s Coordinating Center (NACC) cohort, we related neuropathologic markers of cerebrovascular disease with clinical severity of LBD both cross-sectionally and longitudinally.

Effects of cerebrovascular lesions (CVLs) on cognition in LBD remain uncertain. Most studies use white matter hyperintensity (WMH) indices and report associations with decline, often β-amyloid–dependent. Whether WMHs reflect vascular injury or secondary neurodegeneration is unclear. Autopsy-confirmed microinfarcts provide a further opportunity to  examine CVL-related cognitive impairment in LBD.

Autopsy-confirmed LBD cases from the NACC cohort were analyzed. Cross-sectional associations of microinfarcts with neuropsychological test scores, stratified by amyloid co-pathology and adjusted for age and sex, were assessed using logistic regression models. Longitudinal mixed effects models were used to relate the neuropathologic presence of microinfarcts with repeated neuropsychological testing, stratified by amyloid co-pathology and adjusted for age, sex, and baseline neuropsychological test scores.

The presence of microinfarcts in cases of autopsy-confirmed LBD had a paradoxical association with better cognitive performance, both cross-sectionally and longitudinally. When stratified by amyloid co-pathology status, amyloid-positive individuals with microinfarcts had a faster rate of cognitive decline compared to amyloid-negative individuals without microinfarcts.

Paradoxically, we found an inverse association between the presence of microinfarcts and clinical severity of LBD in the NACC cohort, suggesting that microinfarcts do not independently worsen decline and highlighting the need to further explore their potential modifying effect on LBD. Notably, amyloid pathology emerged as the main driver of cognitive decline.