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 (VO 2peak ), 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.