Impact of Cerebral Microbleeds on Tau-Associated Cognitive and Structural Decline

BACKGROUND AND OBJECTIVES: Cognitive impairment in older adults is influenced by coexisting β-amyloid (Aβ), tau, and cerebral small vessel disease (CSVD). Cerebral microbleeds (CMBs) are associated with Aβ and CSVD, but their role on tau-related neurodegeneration remains unclear. We investigated whether the CMBs modify tau-related disease progression. METHODS: F-MK-6240 PET for tau at baseline. Cognitive tests were performed annually and MRI at 2 years. Cognitive decline was defined by score changes over this period and cortical atrophy as annual cortical thickness change. Linear regression analyses were conducted after stratifying by total or lobar CMB presence. RESULTS: -for-interaction = 0.045) scores. Imaging analysis showed more extensive cortical atrophy in the CMB group, but tau-related cortical atrophy was widespread only in the non-CMB group and minimal in the CMB group. DISCUSSION: In the non-CMB group, tau burden was strongly associated with cognitive decline and cortical atrophy. By contrast, the CMB group exhibited greater CSVD burden and pronounced neurodegeneration not explained by tau, suggesting that additional mechanisms such as CSVD related to cerebral amyloid angiopathy or neuroinflammation may contribute to disease progression in this group.