Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults

Abstract

Objective:Physical activity has been associated with a decreased risk for dementia, but the mechanisms underlying this association remain to be determined. Our objective was to assess whether cardiovascular risk factors mediate the association between physical activity and brain integrity markers in older adults.Methods:Participants from the Age-Well study underwent, at baseline, a physical activity questionnaire, cardiovascular risk factors collection (systolic blood pressure, body mass index [BMI], current smoker status, HDL-cholesterol, total-cholesterol, insulin) and multimodal neuroimaging (structural-MRI, diffusion-MRI, FDG-PET, Florbetapir-PET). Multiple regressions were conducted to assess the association between physical activity, cardiovascular risk factors, and neuroimaging. Mediation analyses were performed to test whether cardiovascular risk factors mediated the associations between physical activity and neuroimaging.Results:134 cognitively unimpaired older adults (≥65 years) were included. Higher physical activity was associated with higher grey matter (GM) volume (ß=0.174, p=0.030) and cerebral glucose metabolism (ß=0.247, p=0.019), but not with amyloid deposition or white matter integrity. Higher physical activity was associated with lower insulin and BMI, but not with the other cardiovascular risk factors. Lower insulin and BMI were related to higher GM volume, but not to cerebral glucose metabolism. When controlling for insulin and BMI, the association between physical activity and cerebral glucose metabolism remained unchanged, while the association with GM volume was lost. When insulin and BMI were entered in the same model, only BMI remained a significant predictor of GM volume. Mediation analyses confirmed that insulin and BMI mediated the association between physical activity and GM volume. Analyses were replicated within Alzheimer’s disease-sensitive regions, and results remained overall similar.Conclusions:The association between physical activity and GM volume is mediated by changes in insulin and BMI. In contrast, the association with cerebral glucose metabolism seems to be independent from cardiovascular risk factors. Older adults practicing physical activity have cardiovascular benefits, through the maintenance of a lower BMI and insulin, resulting in greater structural brain integrity. This study has strong implications as understanding how physical activity affects brain health may help developing strategies to prevent or delay age-related decline.Trial Registration Information:EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

Exercise and Brain Health

“…The findings from Felisatti et al 3 add to a growing literature relating physical activity with gray matter volumes. 4,5 Physical exercise may be hypothesized to influence brain structural integrity through multiple pathways, including directly through a neuroprotective effect (e.g., neuronal plasticity, synaptic function, neurotrophic environment) or indirectly via effects on cerebrovascular health.…”

“…Specific targeting of these mechanisms underlying the lifestyle–brain health relationship could represent an avenue toward optimizing cognitive function with aging. In this issue of Neurology® , Felisatti et al 3 use clinical, demographic, and retrospective cross-sectional imaging data to hone in on one of these mechanisms. Examining 134 cognitively unimpaired adults aged 65 years and older, the authors report that higher physical activity (assessed by patient surveys) was associated with higher brain gray matter volume (as an indicator of brain structural health), and that lower blood insulin levels and lower body mass index (BMI) statistically mediated this association.…”

Light intensity physical activity is beneficially associated with brain volume in older adults with high cardiovascular risk

“…Regular physical activity is considered to regulate the cellular redox state of the brain, and this antioxidative effect may support neuroprotection ( 39 ). In addition, physical activity also helps reduce proinflammatory conditions such as obesity and insulin disturbances ( 21 ). These anti-inflammatory effects may counteract neurodegeneration.…”

“…As described above, physical activity directly induces the release of neurotrophic factors, and activates neurogenesis and synaptic plasticity that independently protect the brain. On the other hand, physical activity also reduces inflammation induced by cardiovascular risk factors, which in turn indirectly improves growth factor signaling and mitigates their adverse effects on the brain ( 21 ). Taking these into account, the high cardiovascular risk group in this study may be in a relatively elevated inflammatory state and may be more likely to benefit from the anti-inflammatory effects of physical activity.…”

“…Moreover, a previous study suggests that LPA as well as MVPA were favorably associated with both cardiovascular risk factors and absolute cardiovascular risk level in older females without cardiovascular diseases ( 20 ), and these cardiovascular risk factors are known to be associated with brain health ( 2 , 3 ). Additionally, Felisatti et al ( 21 ) performed mediation analysis and showed that the relationship between physical activity and brain volume may be mediated by cardiovascular risk factors in cognitively unimpaired older adults. Therefore, we hypothesized that LPA, as well as MVPA, would be beneficially associated with brain volume via better control of cardiovascular risk, even in populations at high cardiovascular risk level.…”