Abstract
OBJECTIVE: To investigate the associations between cerebral microhemorrhages (CMH) and cognitive decline across the Alzheimer's dementia continuum. METHODS: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we studied 619 participants, categorized into 221 cognitively normal (CN) participants, 281 patients with mild cognitive impairment (MCI), and 117 patients with Alzheimer's disease (AD). CMH prevalence and distribution were determined using T2-weighted magnetic resonance imaging (MRI), focusing on the frontal, occipital, and parietal subcortical regions of interest (ROIs).Clinical dementia rating scale sum of boxes (CDR-SB) and mini-mental state examination (MMSE) were used for diagnosis and composite cognitive scores regarding visuospatial abilities, language, memory, and executive functions were used as outcome variables. Age, gender, and APOE ε4 positivity status were used as covariates. RESULTS: The AD group displayed significantly elevated tau and P-tau levels compared to MCI and CN groups (p < 0.001). APOE ε4 positivity was 67.5% in the AD group, surpassing the 50.2% in MCI and 29% in CN individuals (p < 0.001). Cognitive assessments revealed that the AD group's CDR-SB score and MMSE both significantly differed from these scores in the MCI and CN groups (p < 0.001). Overall, CMH prevalence was 27.7%, with a predominant distribution in the frontal subcortical ROIs. MCI subjects with CMH showed notably diminished ADNI Visuospatial Composite Scores compared to those without CMH. Age significantly predicted CMH in CN and MCI (p < 0.05). In AD participants, APOE ε4 heterozygotes (p = 0.02) and homozygotes (p = 0.01) hadincreased CMH likelihood. CONCLUSION: CMHs are significantly associated with cognitive decline in patients with MCI. This association is more prominent in regard to the decline in visuospatial abilities.