INTRODUCTION: Neuronal health as a potential underlying mechanism of the beneficial effects of exercise has been understudied in humans. Furthermore, there has been limited consideration of potential moderators (e.g., cardiovascular health) on the effects of exercise. METHODS: Clinically normal middle-aged and older adults completed a validated questionnaire about exercise engagement over a 10-year period (n = 75; age 63 ± 8 years). A composite estimate of neuronal injury was formulated that included cerebrospinal fluid-based measures of visinin-like protein-1, neurogranin, synaptosomal-associated protein 25, and neurofilament light chain. Cardiovascular risk was estimated using the Framingham Risk Score. RESULTS: Cross-sectional analyses showed that greater exercise engagement was associated with less neuronal injury in the group with lower cardiovascular risk (p = 0.008), but not the group with higher cardiovascular risk (p = 0.209). DISCUSSION: Cardiovascular risk is an important moderator to consider when examining the effects of exercise on cognitive and neural health, and may be relevant to personalized exercise recommendations. Highlights: We examined the association between exercise engagement and neuronal injury. Vascular risk moderated the association between exercise and neuronal injury. Cardiovascular risk may be relevant to personalized exercise recommendations.

Original languageEnglish
Pages (from-to)4454-4462
Number of pages9
JournalAlzheimer's and Dementia
Issue number10
StatePublished - Oct 2023


  • NfL
  • Ng
  • SNAP-25
  • VILIP-1
  • cardiovascular risk


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