Müller S, et al. - This investigation was planned to assess the cross-sectional associations of physical activity (PA) with cognitive performance, functional status, cognitive decline, and Alzheimer's disease (AD) biomarkers in cerebrospinal fluid by analyzing data of 372 people partaking at the Dominantly Inherited Alzheimer Network study. Compared to people with low PA, mutation carriers with high PA (ie, exercise duration ≥ 150 min/week) exhibited significantly better cognitive and functional performance and significantly less AD-like pathology in cerebrospinal fluid. Compared with low exercisers, mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later. Even in individuals with genetically driven autosomal dominant AD, these outcomes supported a positive impact of PA on cognition and AD pathology.