Paper ID: 2410.12809

Cerebral microbleeds: Association with cognitive decline and pathology build-up

Saima Rathore, Jatin Chaudhary, Boning Tong, Selen Bozkurt

Cerebral microbleeds, markers of brain damage from vascular and amyloid pathologies, are linked to cognitive decline in aging, but their role in Alzheimer's disease (AD) onset and progression remains unclear. This study aimed to explore whether the presence and location of lobar microbleeds are associated with amyloid-$\beta$ (A$\beta$)-PET, tau tangle formation (tau-PET), and longitudinal cognitive decline. We analyzed 1,573 ADNI participants with MR imaging data and information on the number and location of microbleeds. Associations between lobar microbleeds and pathology, cerebrospinal fluid (CSF), genetics, and cognition were examined, focusing on regional microbleeds and domain-specific cognitive decline using ordinary least-squares regression while adjusting for covariates. Cognitive decline was assessed with ADAS-Cog11 and its domain-specific sub-scores. Participants underwent neuropsychological testing at least twice, with a minimum two-year interval between assessments. Among the 1,573 participants (692 women, mean age 71.23 years), 373 participants had microbleeds. The presence of microbleeds was linked to cognitive decline, particularly in the semantic, language, and praxis domains for those with temporal lobe microbleeds. Microbleeds in the overall cortex were associated with language decline. Pathologically, temporal lobe microbleeds were associated with increased tau in the overall cortex, while cortical microbleeds were linked to elevated A$\beta$ in the temporal, parietal, and frontal regions. In this mixed population, microbleeds were connected to longitudinal cognitive decline, especially in semantic and language domains, and were associated with higher baseline A$\beta$ and tau pathology. These findings suggest that lobar microbleeds should be included in AD diagnostic and prognostic evaluations.

Submitted: Sep 30, 2024