Associations Between Cardiorespiratory Fitness, Adiposity, and White Matter Integrity

White matter (WM) is essential for transmitting neural signal between brain regions, and supporting healthy brain aging and cognitive function. Risk for WM deterioration is heightened in overweight and obesity, whereas increasing cardiorespiratory fitness may promote WM integrity. However, there is a lack of research comparing adiposity and cardiorespiratory fitness with WM. Further, it is not clear whether increasing cardiorespiratory fitness may outweigh the influence of excess adiposity on WM integrity in middle adulthood. In a sample of adults with overweight and obesity, we examined whether cardiorespiratory fitness and adiposity associate with WM integrity, both independently and jointly. We assessed WM pathways sensitive to cardiorespiratory fitness, adiposity, or both, and tested potential interactions. Baseline data from 125 middle-aged participants (Mage = 44.33 ± 8.60), with overweight or obesity (MBMI = 32.45 ± 4.19), were included in the study. Fitness was assessed via a submaximal graded exercise test. To quantify adiposity, whole body estimates of body fat % were calculated using dual-energy X-ray absorptiometry. Diffusion weighted images were acquired during an MRI protocol. We conducted whole-brain voxelwise analyses using the FMRIB’s Software Library randomise function to examine main effects of adiposity and fitness, as well as the interaction term, on WM integrity. After controlling for age, gender, and years of education, there were no significant main effects of adiposity or cardiorespiratory fitness on FA (all p > .05). There was a significant interaction (p = .03) such that with higher fitness levels, greater adiposity was associated with higher WM integrity, whereas with lower fitness levels greater adiposity was negatively associated with WM integrity. This pattern of findings was unexpected, and may be a function of the unique nature of the sample or related to the confounding effects of WM lesions or local inflammation. Future work may focus on accounting for the influence of WM lesions, and extending the analysis to older adults and patient populations

Interactive Effects of Physical Activity and APOE-ε4 On White Matter Tract Diffusivity in Healthy Elders

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer\u27s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts

Comparing aging and fitness effects on brain anatomy

Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors

Neuroprotective Effects of Cardiorespiratory Fitness on White Matter Integrity and Cognition Across the Adult Lifespan

Objective: Cardiorespiratory fitness (CRF) is associated with decreased risk for cognitive decline. Accumulating evidence has linked CRF to more conserved white matter (WM) integrity and better cognitive performance in older adults. Additional research is needed to determine: (1) which WM tracts are most strongly related to CRF, (2) whether CRF-related benefits on WM translate to enhanced executive functioning (EF), and (3) if the neuroprotective effects of CRF are age-dependent. This study aimed to evaluate CRF as an intervention for modulating decreased WM integrity and EF in aging. Method: Participants were community-dwelling adults (N = 499; ages 20-85) from the open-access Nathan Kline Institute – Rockland Sample (NKIRS) with CRF (bike test), self-report of physical activity, diffusion tensor imaging (DTI), and EF data. Mixed-effect modeling tested the interaction between CRF and age on WM integrity (global and local microstructure). Significant WM tracts were retained for structural equation modeling to determine whether enhanced microstructure mediated a positive relationship between CRF and EF. Results: Among older participants (age 60), CRF was significantly related to stronger whole-brain (z-score slope = 0.11) and local WM integrity within five tracts (z-score slope range = 0.14 – 0.20). In support of the age-dependent hypothesis, the CRF–WM relationship was comparably weaker (z-score slopes 0.11) and more limited (one WM tract) in younger adults. CRF was more consistently related to WM than self-report of physical activity. Although CRF was linked to enhanced WM integrity, its potential benefits on EF were not directly observed. Conclusion: The findings highlight the importance of positive lifestyle factors, such as physical activity, in maintaining brain health in senescence. CRF may selectively preserve a collection of anterior and posterior WM connections related to visuomotor function

Cardiorespiratory Fitness Diminishes the Effects of Age on White Matter Hyperintensity Volume

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults

Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

Citation: Wong, C. N., Chaddock-Heyman, L., Voss, M. W., Burzynska, A. Z., Basak, C., Erickson, K. I., . . . Kramer, A. F. (2015). Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults. Frontiers in Aging Neuroscience, 7, 10. doi:10.3389/fnagi.2015.00154Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59-80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function

The neuroprotective effects of endurance training on the aging brain

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested the hypothesis that changes in autonomic outflow across the adult age-span are related to cerebral cortex atrophy and function, and are sensitive to the effects of physical fitness. Study 1 demonstrated that advancing age impairs the heart rate (HR) response and modifies the cortical patterns associated with cardiovascular control during isometric handgrip (IHG), and is further exacerbated with coronary artery disease. The utility of aerobic exercise to prevent these age-related changes is not known. Study 2 revealed that lifelong, sustained aerobic training builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span, but did not alter the rate of age-related cortical or subcortical decline. Study 3 demonstrated that cardiorespiratory fitness correlated strongly with whole-brain cortical thickness, while markers of autonomic outflow were specifically associated with cortical mass at the MPFC. Importantly, the strength of the relationship between autonomic variables and cortical thickness was determined by age, and was not altered following adjustments for cardiorespiratory fitness. Study 4 revealed a positive effect of high fitness on MPFC activation, yet did not affect absolute HR responses to IHG in this age range. Therefore, this series of studies implicates cortical atrophy in the frontal lobe as a contributor to the dysregulation of autonomic outflow associated with advancing age, and suggests that high cardiorespiratory fitness delays the age-related decline in cortical circuitry associated with cardiovascular control

Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function

Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

Citation: Wong, C. N., Chaddock-Heyman, L., Voss, M. W., Burzynska, A. Z., Basak, C., Erickson, K. I., . . . Kramer, A. F. (2015). Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults. Frontiers in Aging Neuroscience, 7, 10. doi:10.3389/fnagi.2015.00154Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59-80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function

Higher physical fitness levels are associated with less language decline in healthy ageing

Healthy ageing is associated with decline in cognitive abilities such as language. Aerobic fitness has been shown to ameliorate decline in some cognitive domains, but the potential benefits for language have not been examined. In a cross-sectional sample, we investigated the relationship between aerobic fitness and tip-of-the-tongue states. These are among the most frequent cognitive failures in healthy older adults and occur when a speaker knows a word but is unable to produce it. We found that healthy older adults indeed experience more tip-of-the-tongue states than young adults. Importantly, higher aerobic fitness levels decrease the probability of experiencing tip-of-the-tongue states in healthy older adults. Fitness-related differences in word finding abilities are observed over and above effects of age. This is the first demonstration of a link between aerobic fitness and language functioning in healthy older adults