ArticleJournal of Alzheimer's disease : JAD2023
Association of Physical Inactivity with MRI Markers of Brain Aging: Assessing Mediation by Cardiometabolic and Epigenetic Factors.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Divergent Multimodal Age-Association Profiles Across the Human Brain.Nature communications · 2026Article
- Cleaning and pre-processing of actigraphy data for physical activity and sleep research: a scoping review.Physiological measurement · 2026Article
- Voluntary Long-Term Exercise by Female Mice Modulates Anxiety-Like Behavior and Motor Function but Minimally Impacts Acute Oxidative Injury in the Central Nervous System.The European journal of neuroscience · 2025Article
- Cardiovascular disease as a mediator in the relationship between lifestyle risk factors and cognitive outcomes: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?International journal of molecular sciences · 2024Review
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Authors and funding
11 authors.
Funding
Abstract
introductionCardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process.
objectiveTo determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology.
methodsWe included dementia and stroke free participants from the Framingham Heart Study Third Generation and Offspring cohorts who had accelerometery and brain MRI data (n = 2,507, 53.9% women, mean age 53.9 years). We examined mediation by the 2017-revised Framingham Stroke Risk Profile (FSRP, using weights for age, cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications, and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of physical inactivity with brain aging, adjusting for age, age-squared, sex, accelerometer wear time, cohort, time from exam-to-MRI, and season. We similarly assessed mediation by an epigenetic age-prediction algorithm, GrimAge, in a smaller sample of participants who had DNA methylation data (n = 1,418).
resultsFSRP and HOMA-IR explained 8.3-20.5% of associations of higher moderate-to-vigorous physical activity (MVPA), higher steps, and lower sedentary time with higher brain volume. Additionally, FSRP and GrimAge explained 10.3-22.0% of associations of physical inactivity with lower white matter diffusivity and FSRP explained 19.7% of the association of MVPA with lower free water accumulation.
conclusionOur results suggest that cardiometabolic risk factors and epigenetic patterns partially mediate the associations of physical inactivity with lower brain volume, higher white matter diffusivity, and aggregation of free water in the extracellular compartments of the brain.
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