Better fitness was linked to healthier brain structure, but not better memory

Objective fitness testing, brain imaging, blood biomarkers, and cognitive assessments probe whether physical conditioning helps aging brains resist pathology or remain resilient when it develops.

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In a recent study published in the journal npj Aging, researchers evaluated the associations of objectively measured aerobic and muscular fitness with brain structure, pathology, and cognition in cognitively unimpaired older adults (aged 60-94 years).

The study sample cohort comprised 353 community-dwelling cognitively unimpaired participants whose brain pathology and cognitive performance were measured to examine whether physical conditioning supports brain maintenance (resisting declines in neural resources and age-related neuropathology) or cognitive reserve (coping with pathology while maintaining cognitive function).

Study findings revealed that physical fitness was not directly associated with baseline global cognition or episodic memory. Higher muscular capacity was associated with significantly lower basal ganglia perivascular space (PVS) volume. Enlarged PVS may signal impaired brain homeostasis and is linked to cerebral small vessel disease. The authors identified glymphatic clearance and cerebrovascular integrity as possible mechanisms that warrant further study.

Concurrently, higher aerobic fitness was associated with greater total gray matter (GM) volume and a thicker medial temporal lobe (MTL) cortex. The authors interpreted these cross-sectional associations as consistent with better brain health and brain maintenance, but the study cannot establish that fitness preserved brain structure over time.

Background

Aging is associated with progressive brain tissue atrophy, cerebral small vessel disease, and the accumulation of Alzheimer's disease (AD)-related amyloid-beta (Aβ) plaques and phosphorylated tau (p-tau) tangles.

The rate and extent of cognitive decline vary widely, and some older adults maintain high cognitive performance as they age or with disease progression. To understand why certain individuals preserve cognitive acuity, neuroscientists have previously evaluated ‘brain maintenance’ (resistance to loss of neural resources and neuropathological change) and ‘cognitive reserve’ (an individual’s capacity to function in the presence of pathology).

Research has linked physical activity with measures of brain structure and cognitive performance, but evidence that it contributes to cognitive reserve remains mixed. Many cross-sectional studies also rely on self-reported questionnaires, which are known to be prone to recall errors, particularly in elderly cohorts.

To address limitations in previous research, the researchers combined objective physiological fitness measures with detailed neuropsychological testing, blood biomarkers, and multi-modal brain imaging in a cognitively unimpaired older cohort.

About the study

The present study aimed to address this knowledge gap by objectively measuring muscular capacity and aerobic capacity in older adults (aged 60-94) and estimating their associations with brain structure, pathology, and cognitive performance. The study’s sample cohort comprised 353 cognitively unimpaired older adults (177 females; mean age = 72.77 years; mean education = 14.93 years) from the German Collaborative Research Centre 1436 cohort.

The study first quantified all participants' fitness using a composite muscular capacity score that combined maximal handgrip strength, the Timed Up and Go (TUG) mobility test, and appendicular skeletal muscle mass (ASMM) measured by bioelectrical impedance analysis (BIA).

A subset of 140 participants was evaluated for aerobic capacity, quantified using a symptom-limited cardiopulmonary exercise test (CPET) on a cycle ergometer (expressed as VO2 max).

The study’s neurobiological endpoints were assessed using high-resolution 3-Tesla (3T) magnetic resonance imaging (MRI) to estimate participants’ gray matter volume, MTL thickness, hippocampal volumes, white matter hyperintensities, and basal ganglia and centrum semiovale perivascular spaces, and [18F]PI-2620 positron emission tomography (PET) to evaluate their medial temporal lobe tau deposition. The blood panel included Aβ1-42/Aβ1-40, p-tau217, and glial fibrillary acidic protein (GFAP), as well as the neuroplasticity-related markers BDNF, vascular endothelial growth factor">VEGF, and Cathepsin B.

Finally, the study employed standardized cognitive assessments to measure participants’ delayed verbal recall using the Verbal Learning and Memory Test (VLMT) and global cognition using the Preclinical Alzheimer's Cognitive Composite (PACC5), with CERAD-Plus and the Rey-Osterrieth Complex Figure Test providing further global and visuospatial memory measures.

Study findings

The cognitive regression models, adjusted for age, sex, and education, found no significant associations between muscular or aerobic fitness and global cognition or episodic memory. Analyses of brain pathology, however, provided partial support for brain maintenance.

Results showed that higher muscular capacity was significantly associated with lower basal ganglia perivascular space (PVS) volume, and component analysis indicated that better TUG performance was also associated with lower PVS volume. Aerobic fitness showed a weaker association with lower basal ganglia PVS volume, but this association was not statistically significant after multiple-comparison correction.

No significant associations were found between either fitness measure and the remaining pathology markers, including plasma AD biomarkers, MTL tau burden, or white matter hyperintensities. Participants’ VO2 max was associated with greater total gray matter volume and a thicker medial temporal cortex.

Muscular capacity showed an unexpected association with lower right anterior hippocampal volume, driven mainly by ASMM, while better TUG performance was associated with greater total gray matter volume and MTL thickness. The authors treated these muscle-mass findings cautiously because ASMM may partly reflect body size or composition rather than functional muscular fitness.

Within the VO2 max subgroup, greater MTL tau burden was associated with poorer delayed verbal recall. VO2 max did not moderate the tau-memory association. After accounting for tau burden, it was independently associated with better delayed verbal recall and explained an additional 7.6% of the variance in delayed verbal recall. This offered limited, rather than definitive, evidence for cognitive reserve.

Conclusions

The research used objective fitness testing and multi-modal brain measures to show distinct associations between physical fitness and markers of brain health in cognitively unimpaired older adults. Its findings were more consistent with brain maintenance than with cognitive reserve, while the reserve analyses produced limited evidence rather than a clear effect.

The cross-sectional design prevents causal conclusions. The cohort was also highly educated, community-dwelling, cognitively normal, and restricted to Caucasian German participants without major neurological or systemic disease; the VO2 max subgroup met additional exercise-safety criteria and was even healthier. Several imaging and biomarker measures were available only in smaller subsamples.

Future longitudinal and interventional studies are needed to test whether improvements in aerobic or muscular fitness alter PVS burden, brain structure, or resilience to age-related pathology over time.

Journal reference:

• Schwarck, S., Behrenbruch, N., Schumann-Werner, B., Molloy, E. N., Garcia-Garcia, B., Hochkeppler, A., Fischer, L., Büchel, A. T., Incesoy, E. I., Bernal, J., Coello, R. D., Valdés-Hernández, M. D., Wardlaw, J. M., Vockert, N., Müller, P., Behnisch, G., Morgado, B., Esselmann, H., Seidenbecher, C. I., . . . Maass, A. (2026). Associations of physical fitness with brain structure, pathology and cognition in cognitively normal older adults. Npj Aging, 12(1), 129. DOI: 10.1038/s41514-026-00512-4, https://www.nature.com/articles/s41514-026-00512-4