Physical activity changes during midlife link to brain integrity and amyloid burden

Akinci, Muge; Aguilar Dominguez, Pablo; Palpatzis, Eleni; Shekari, Mahnaz; Garcia Prat, Marina; Deulofeu, Carme; Fauria, Karine; García Aymerich, Judith; Gispert, Juan Domingo; Suárez-Calvet, Marc; Grau, Oriol (Grau Rivera); Sánchez Benavides, Gonzalo; Arenaza Urquijo, Eider M.; ALFA Study

doi:http://dx.doi.org/10.1002/alz.70007

Physical activity changes during midlife link to brain integrity and amyloid burden

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Akinci M, Aguilar-Domínguez P, Palpatzis E, Shekari M, García-Prat M, Deulofeu C, et al. Physical activity changes during midlife link to brain integrity and amyloid burden. Alzheimers Dement. 2025 May;21(5):e70007. DOI: 10.1002/alz.70007

Abstract

Introduction: Evidence suggests that midlife physical activity may reduce Alzheimer's disease (AD) risk. In at-risk individuals, we investigated midlife physical activity changes in relation to AD-related pathologies. Methods: We included 337 cognitively unimpaired adults with baseline and follow-up physical activity evaluations within 4.07 ± 0.84 years. We performed multiple regressions considering follow-up amyloid-PET burden and MRI-based medial temporal lobe cortical thickness as outcomes. Independent variables encompassed changes in adherence to World Health Organization (WHO)-recommended physical activity levels, activity amounts, and sedentary behavior (no activity reported). Results: Remaining sedentary was associated with lower cortical thickness compared to doing limited physical activity, maintaining adherence, or becoming adherent to WHO recommendations. Becoming adherent to recommendations was linked to lower amyloid burden compared to becoming non-adherent. Increased activity amounts showed a dose-dependent association with lower amyloid burden. Discussion: Increasing physical activity and new adherence to WHO recommendations could be key objectives for preventive strategies during midlife. Clinical trial registration information: Registered at Clinicaltrials.gov (identifier: NCT02485730). Highlights: Boosting physical activity in midlife may have beneficial effects in preclinical AD. Physical activity increases relate to lower Aβ burden in a dose-dependent manner. Remaining sedentary links to lower cortical thickness in AD-vulnerable structures. New adherence to WHO-recommended physical activity levels may enhance brain health.