Cardiorespiratory fitness attenuates age-associated aggregation of white matter hyperintensities in an at-risk cohort

Abstract

BackgroundAge is the cardinal risk factor for Alzheimer’s disease (AD), and white matter hyperintensities (WMH), which are more prevalent with increasing age, may contribute to AD. Higher cardiorespiratory fitness (CRF) has been shown to be associated with cognitive health and decreased burden of AD-related brain alterations in older adults. Accordingly, the aim of this study was to determine whether CRF attenuates age-related accumulation of WMH in middle-aged adults at risk for AD.MethodsOne hundred and seven cognitively unimpaired, late-middle-aged adults from the Wisconsin Registry for Alzheimer’s Prevention underwent 3 T magnetic resonance imaging and performed graded maximal treadmill exercise testing from which we calculated the oxygen uptake efficiency slope (OUES) as our measure of CRF. Total WMH were quantified using the Lesion Segmentation Tool and scaled to intracranial volume. Linear regression adjusted for APOE4 carriage, family history, body mass index, systolic blood pressure, and sex was used to examine relationships between age, WMH, and CRF.ResultsAs expected, there was a significant association between age and WMH (p < .001). Importantly, there was a significant interaction between age and OUES on WMH (p = .015). Simple main effects analyses revealed that the effect of age on WMH remained significant in the Low OUES group (p < .001) but not in the High OUES group (p = .540), indicating that higher CRF attenuates the deleterious age association with WMH.ConclusionsHigher CRF tempers the adverse effect of age on WMH. This suggests a potential pathway through which increased aerobic fitness facilitates healthy brain aging, especially among individuals at risk for AD.

Causal structure discovery identifies risk factors and early brain markers related to evolution of white matter hyperintensities

“…Consistent with previous findings ( Gray et al, 2020 , Fleischman et al, 2015 ), we found smoking is associated with WMH which were confirmed by both the regression and CSD analyses. These associations between cigarette exposure and WMH were also well established in two large samples from the UK Biobank ( Maillard et al, 2015 , Vesperman et al, 2018 ). Our findings further provide evidence for an association between smoking effects and poorer WM integrity.…”

Cardiorespiratory fitness diminishes the effects of age on white matter hyperintensity volume

“…Lower cerebral blood flow is associated with higher WMH volume [38,55]. Further, older middle-age adults who are enriched for Alzheimer's disease risk factors, but who have high CRF, show lower WMH volume than peers with lower CRF [56]. Collectively, exercise-induced improvements in vascular health likely augment cerebrovascular function by improving cerebral circulation.…”

Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson's disease

“…Although cerebral WM changes are common in aging populations, the degree to which they are associated with cognitive and motor symptoms varies between individuals, and may be mediated by protective factors that influence cerebral reserve such as education (Blume et al, 2017) and cardiorespiratory fitness (Johnson et al, 2012; Vesperman et al, 2018). Parkinson's disease, which causes underlying dysfunction of frontal-striatal circuits, represents a preexisting strike against cognitive reserve.…”