Journal Article

DZNE-2026-00985

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Associations of physical fitness with brain structure, pathology and cognition in cognitively normal older adults.

Schwarck, S. (First author)DZNE* ; Behrenbruch, N.DZNE* ; Schumann-Werner, B.DZNE* ; Molloy, E. N.DZNE* ; Garcia-Garcia, B.DZNE* ; Hochkeppler, A.DZNE* ; Fischer, L.DZNE* ; Büchel, A.-T.DZNE* ; Incesoy, E. I.DZNE* ; Bernal, J.DZNE* ; Coello, R. D. ; Valdés-Hernández, M. D. C. ; Wardlaw, J. M. ; Vockert, N.DZNE* ; Müller, P.DZNE* ; Behnisch, G. ; Marcos Morgado, B.Extern* ; Esselmann, H. ; Seidenbecher, C. I. ; Schott, B. H.DZNE* ; Barthel, H. ; Sabri, O.Extern* ; Wiltfang, J.DZNE* ; Kreissl, M. C.DZNE* ; Düzel, E.DZNE* ; Maass, A. (Last author)DZNE*

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41514-026-00512-4

Abstract: The role of physical fitness in cognitive reserve and brain maintenance remains unclear. We investigated the associations of muscular and aerobic fitness (VO2max) with markers of brain health and cognition in 353 cognitively unimpaired older adults (mean age = 72.77 ± 7.95 years; 177 females). Muscular fitness comprised handgrip strength, appendicular skeletal muscle mass, and Timed-Up-and-Go performance. Blood biomarkers of Alzheimer's pathology (Aβ1-42/Aβ1-40, p-tau217, GFAP) and neuroplasticity (BDNF, VEGF, Cathepsin-B), gray matter (GM) volume and thickness, medial temporal lobe (MTL) tau burden ([¹⁸F]PI-2620 PET), white matter hyperintensities, and perivascular spaces (PVS) were assessed. Higher muscular capacity was associated with lower basal ganglia PVS volume, whereas aerobic fitness was related to greater MTL thickness and GM volume. Although fitness did not moderate pathology-cognition associations, VO₂max explained additional variance in verbal memory beyond tau. These findings indicate distinct associations of fitness with brain health, while providing limited support for cognitive reserve. Trial Registration: The study was registered in the German Clinical Trials Register (DRKS00032449; date of registration: 2025-05-07; recruiting ongoing).

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Contributing Institute(s):

1. Multimodal Neuroimaging (AG Maaß)
2. Clinical Neurophysiology and Memory (AG Düzel)
3. Neuroprotection (AG Müller)
4. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
5. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
6. Core MR PET (Core MR PET)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
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