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.
Highlights
Age 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
Peak oxygen consumption (VO2 peak) is traditionally regarded as the gold standard measure for cardiorespiratory fitness (CRF) [2], older adults as a whole are known to struggle with meeting the criteria for peak effort during maximal graded exercise testing (GXT)
We hypothesized that older age would be associated with more WMH, but that higher CRF would attenuate this deleterious effect of aging on WMH
Summary
Age 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. Cardiorespiratory fitness (CRF), an index of habitual physical activity, has been associated with preserved cognitive function and brain structure in older adults [10, 20, 21, 25, 27, 38]. It has been associated with a lower risk of dementia in the elderly [14, 18, 46]. We hypothesized that older age would be associated with more WMH, but that higher CRF would attenuate this deleterious effect of aging on WMH
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