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Basic Science and Pathogenesis.
Lauren Oberlin1,2, Audrey M Collins3, Eric D Vidoni4
1AdventHealth Neuroscience Institute, Orlando, FL, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Regular physical activity (PA) and higher cardiorespiratory fitness (CRF) are linked to better cognitive function and brain health in older adults. Maintaining fitness may help offset neurodegenerative changes, particularly in those with preclinical Alzheimer's Disease (AD) pathology.
Area of Science:
- Neuroscience
- Gerontology
- Preventive Medicine
Background:
- Physical activity (PA) is a potential strategy for preserving cognitive function and reducing dementia risk.
- Critical questions remain regarding the effectiveness, dosing, and mechanisms of PA's impact on cognition.
- Understanding these factors is crucial for developing precise preventive approaches and behavioral interventions.
Purpose of the Study:
- To investigate the clinical impact and biological pathways of aerobic exercise on cognition and brain health in older adults.
- To present preliminary cross-sectional and longitudinal findings from a phase 3 clinical trial (IGNITE study).
- To examine dose-response relationships and influencing factors on exercise effects.
Main Methods:
- The IGNITE study is a 12-month randomized trial involving 648 older adults.
- Participants were assigned to 150 min/week moderate aerobic exercise, 225 min/week moderate aerobic exercise, or 150 min/week light-intensity stretching/toning (control).
- Data collected included cognitive assessments, brain MRI, PET amyloid scans, AD-related blood biomarkers, accelerometry, and cardiorespiratory fitness (CRF) at baseline and 12 months.
Main Results:
- Higher baseline fitness (CRF) correlated with greater hippocampal volume, preserved white matter integrity, and better cognitive performance (executive function, processing speed, memory).
- Greater baseline moderate-to-vigorous PA (MVPA) was associated with better multi-domain cognitive performance and slower brain aging.
- Higher fitness and MVPA related to lower NfL levels, especially in Aβ-positive individuals, suggesting a protective effect against neurodegeneration.
Conclusions:
- Preliminary findings highlight the association between fitness, PA, cognition, brain morphology, and AD biomarkers in cognitively unimpaired older adults.
- The study identified multiple moderators influencing these relationships.
- These findings can inform individualized exercise prescriptions for optimizing cognitive and brain health in aging individuals.
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