Physical activity, aerobic fitness, and AD blood biomarkers: The IGNITE study

Introduction: Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with reduced risk of cognitive decline and dementia, yet their relationships with dementia-related pathophysiology remain unclear. In a community-dwelling older adult cohort, we examined associations between objectively measured PA, CRF, biomarkers of Alzheimer's disease (AD)-related pathology, and cognition. Methods: Participants (n = 648, 71% female, age 69.88 ± 3.75) completed a comprehensive cognitive evaluation, objective assessments of moderate-to-vigorous PA (MVPA) and CRF (VO2peak), and AD-related brain (positron emission tomography [PET] amyloid beta [Aβ]) and blood biomarkers (Aβ1-42/1-40, phosphorylated tau [p-tau]217, p-tau181, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]). Results: Greater MVPA (β = -0.107; p = 0.013) and CRF (β = -0.114; p = 0.027) were associated with lower NfL, but not Aβ PET, p-tau217, Aβ1-42/1-40, or GFAP. Aβ positivity moderated the CRF-NfL relationship, with higher CRF linked to lower NfL specifically among Aβ-positive individuals. NfL mediated relationships between MVPA, CRF, and cognitive performance in select domains. Discussion: Neuroprotective benefits of PA may be conferred through mechanisms influencing neurodegeneration, particularly among those with emerging AD pathology.