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Observational Study
. 2025 May;21(5):e70007.
doi: 10.1002/alz.70007.

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

Muge Akinci  1   2   3   4 , Pablo Aguilar-Domínguez  1   3   4   5 , Eleni Palpatzis  1   2   3   4 , Mahnaz Shekari  2   3   6 , Marina García-Prat  2 , Carme Deulofeu  2 , Karine Fauria  2 , Judith García-Aymerich  1   3   4 , Juan Domingo Gispert  2   3   6   7 , Marc Suárez-Calvet  2   6   8   9 , Oriol Grau-Rivera  2   6   8   9 , Gonzalo Sánchez-Benavides  2   6   8 , Eider M Arenaza-Urquijo  1   2   3   4   6   8 ; ALFA study
Affiliations
Observational Study

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

Muge Akinci et al. Alzheimers Dement. 2025 May.

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.

Keywords: Alzheimer's disease; amyloid‐β; cortical thickness; midlife physical activity; physical activity change; prevention.

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Conflict of interest statement

O.G‐R. has given lectures in symposia sponsored by Roche Diagnostics, and receives support for research (to the institution) from F‐ Hoffmann La Roche. MSC has given lectures in symposia sponsored by Roche Diagnostics, S.L.U, Roche Farma, S.A and Amirall. He has served as a consultant and at advisory boards for Roche Diagnostics International Ltd and Grifols S.L. He was granted with a project funded by Roche Diagnostics International Ltd; payments were made to the institution (BBRC). He received in‐kind support for research (to the institution) from Roche Diagnostics International Ltd, Avid Radiopharmaceuticals, Inc., Eli Lilly and Janssen Research & Development. J.G.‐A. reports speaking and lecture fees from Chiesi España and AstraZeneca Pharmaceuticals LP, not related to the topic of this publication. M.A., P.A.‐D., E.P., M.G.‐P., M.S., C.D., K.F., J.D.G., G.S.‐B., and E.M.A.‐U. declare that they have no competing interests. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Flow diagram showing the selection of study participants. ALFA, ALzheimer's and FAmilies; MLTPAQ, Minnesota Leisure Time Physical Activity Questionnaire; MRI, magnetic resonance imaging; PA, physical activity; PET, positron emission tomography.
FIGURE 2
FIGURE 2
Change in physical activity amounts in relation to brain Aβ burden. Scatter plot illustrating brain amyloid‐β burden (Centiloids) as a function of change in physical activity amounts from baseline to follow‐up. Age, sex, years of education, APOE‐ε4 status, and inter‐individual variability in time between the two physical activity assessments were regressed out from the Centiloid values. Aβ, amyloid‐beta; APOE, apolipoprotein E.
See this image and copyright information in PMC

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