Cerebral microhemorrhage and cognition in preclinical Alzheimer’s disease

Abstract

BACKGROUND: Clarifying whether incident cerebral microhemorrhages (CMHs) contribute to early cognitive or functional decline is increasingly important in the context of anti-amyloid therapies. OBJECTIVE: To determine whether incident CMHs are associated with longitudinal changes in cognition and function in cognitively unimpaired individuals with elevated cerebral amyloid. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of individuals enrolled in the A4 study. Participants underwent serial MRI and cognitive assessments. Natural cubic spline models adjusted for baseline amyloid PET burden, age, sex, education, and APOE ε4 status. MEASUREMENTS: Longitudinal change in the Preclinical Alzheimer Cognitive Composite (PACC), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Cognitive Function Index (CFI), and Activities of Daily Living. RESULTS: Participants who developed ≥2 incident CMHs demonstrated greater longitudinal worsening in CDR-SB (estimate = 0.44; 95% CI, 0.09-0.80; P = .009) and CFI (estimate = 1.37; 95% CI, 0.11-2.60; P = .03), but not in PACC or ADCS ADL. CONCLUSIONS: Incident CMH accumulation was associated with greater longitudinal worsening in global clinical status and participant-reported functional change, but not objective cognitive performance, among cognitively unimpaired individuals with elevated cerebral amyloid.