Exercise and Protection from Age-Related Cognitive Decline.

In this chapter, we review the cross-sectional evidence in healthy human subjects for physical activity and cardiorespiratory fitness to offer neuroprotection and moderate cognitive decline in older age. The role of exercise training on cognition in healthy older adults and those diagnosed with mild cognitive impairment (MCI) is also discussed, including the evidence from neuroimaging studies that document changes to brain structure and function after a period of exercise training and improved fitness. Finally, in reference to animal models, the potential neurophysiological mechanisms for physical activity and exercise to impact human brain health are highlighted.

Sleep and physical activity measures are associated with resting-state network segregation in non-demented older adults.

Greater physical activity and better sleep are associated with reduced risk of cognitive decline and dementia among older adults, but little is known about their combined associations with measures of brain function and neuropathology. This study investigated potential independent and interactive cross-sectional relationships between actigraphy-estimated total volume of physical activity (TVPA) and sleep patterns [i.e., total sleep time (TST), sleep efficiency (SE)] with resting-state functional magnetic resonance imaging (rs-fMRI) measures of large scale network connectivity and positron emission tomography (PET) measures of amyloid-ß. Participants were 135 non-demented older adults from the BIOCARD study (116 cognitively normal and 19 with mild cognitive impairment; mean age = 70.0 years). Using multiple linear regression analyses, we assessed the association between TVPA, TST, and SE with connectivity within the default-mode, salience, and fronto-parietal control networks, and with network modularity, a measure of network segregation. Higher TVPA and SE were independently associated with greater network modularity, although the positive relationship of SE with modularity was only present in amyloid-negative individuals. Additionally, higher TVPA was associated with greater connectivity within the default-mode network, while greater SE was related to greater connectivity within the salience network. In contrast, longer TST was associated with lower network modularity, particularly among amyloid-positive individuals, suggesting a relationship between longer sleep duration and greater network disorganization. Physical activity and sleep measures were not associated with amyloid positivity. These data suggest that greater physical activity levels and more efficient sleep may promote more segregated and potentially resilient functional networks and increase functional connectivity within specific large-scale networks and that the relationship between sleep and functional networks connectivity may depend on amyloid status.

Acute Exercise Improves Large-Scale Brain Network Segregation in Healthy Older Adults.

Introduction: Age-related cognitive decline and mental health problems are accompanied by changes in resting-state functional connectivity (rsFC) indices, such as reduced brain network segregation. Meanwhile, exercise can improve cognition, mood, and neural network function in older adults. Studies on effects of exercise on rsFC outcomes in older adults have chiefly focused on changes after exercise training and suggest improved network segregation through enhanced within-network connectivity. However, effects of acute exercise on rsFC measures of neural network integrity in older adults, which presumably underlie changes observed after exercise training, have received less attention. In this study, we hypothesized that acute exercise in older adults would improve functional segregation of major cognition and affect-related brain networks. Methods: To test this, we analyzed rsFC data from 37 healthy and physically active older adults after they completed 30 min of moderate-to-vigorous intensity cycling and after they completed a seated rest control condition. Conditions were performed in a counterbalanced order across separate days in a within-subject crossover design. We considered large-scale brain networks associated with cognition and affect, including the frontoparietal network (FPN), salience network (SAL), default mode network (DMN), and affect-reward network (ARN). Results: We observed that after acute exercise, there was greater segregation between SAL and DMN, as well as greater segregation between SAL and ARN. Conclusion: These findings indicate that acute exercise in active older adults alters rsFC measures in key cognition and affect-related networks in a manner that opposes age-related dedifferentiation of neural networks that may be detrimental to cognition and mental health.

Sleep Quality Moderates the Associations between Cardiorespiratory Fitness and Hippocampal and Entorhinal Volume in Middle-Aged and Older Adults.

INTRODUCTION/PURPOSE: As individuals age, the entorhinal cortex (ERC) and hippocampus-crucial structures for memory-tend to atrophy, with related cognitive decline. Simultaneously, lifestyle factors that can be modified, such as exercise and sleep, have been separately linked to slowing of brain atrophy and functional decline. However, the synergistic impact of fitness and sleep on susceptible brain structures in aging adults remains uncertain. METHODS: We examined both independent and interactive associations of fitness and subjective sleep quality with regard to ERC thickness and hippocampal volume in 598 middle-aged and older adults from the Human Connectome Lifespan Aging Project. Cardiorespiratory fitness was assessed using the 2-min walk test, whereas subjective sleep quality was measured with the continuous Pittsburgh Sleep Quality Index global score. High-resolution structural magnetic resonance imaging was used to examine mean ERC thickness and bilateral hippocampal volume. Through multiple linear regression analyses, we investigated the moderating effects of subjective sleep quality on the association between fitness and brain structure, accounting for age, sex, education, body mass index, gait speed, and subjective physical activity. RESULTS: We found that greater cardiorespiratory fitness, but not subjective sleep quality, was positively associated with bilateral hippocampal volume and ERC thickness. Notably, significant interaction effects suggest that poor subjective sleep quality was associated with a weaker association between fitness and both hippocampal volume and ERC thickness. CONCLUSIONS: Findings suggest the potential importance of both cardiorespiratory fitness and subjective sleep quality in preserving critical, age-vulnerable brain structures. Interventions targeting brain health should consider potential combined effects of sleep and fitness on brain health.

Actigraphy Estimated Sleep Moderates the Relationship between Physical Activity and Cognition in Older Adults.

Background and Aims: Physical inactivity and poor sleep are common in older adults and may interact to contribute to age- and disease-related cognitive decline. However, prior work regarding the associations among physical activity, and cognition in older adults is primarily limited to subjective questionnaires that are susceptible to inaccuracies and recall bias. Therefore, this study examined whether objectively measured physical activity and sleep characteristics, each estimated using actigraphy, are independently or interactively associated with cognitive performance. Methods: The study included 157 older adults free of dementia (136 cognitively unimpaired; 21 MCI; M age = 71.7) from the BIOCARD cohort. Results: Using multiple linear regression, cognition was regressed on estimated total volume of physical activity (TVPA), sleep efficiency (SE), wake after sleep onset (WASO), and total sleep time (TST) (adjusted for age, sex, education, diagnosis, vascular risk factors, and Apolipoprotein E (APOE)-e4 genetic status). Models were also run for domain-specific cognitive composite scores. TVPA and SE each were positively associated with a global cognitive composite score. TVPA was positively associated with executive function and language composites, and SE was positively related to executive function, visuospatial, and language composites. Importantly, a TVPA by SE interaction (p = 0.015) suggested that adults with the poorest SE experienced the greatest benefit from physical activity in relation to global cognition. The other sleep metrics were unrelated to cognitive performance. Conclusion: These results suggest that TVPA and SE may synergistically benefit cognition in older adults.

Hippocampal functional connectivity mediates the association between cardiorespiratory fitness and cognitive function in healthy young adults.

OBJECTIVE: Higher cardiorespiratory fitness (CRF) induces neuroprotective effects in the hippocampus, a key brain region for memory and learning. We investigated the association between CRF and functional connectivity (FC) of the hippocampus in healthy young adults. We also examined the association between hippocampal FC and neurocognitive function. Lastly, we tested whether hippocampal FC mediates the association between 2-Min Walk Test (2MWT) and neurocognitive function. METHODS: 913 young adults (28.7 ± 3.7 years) from the Human Connectome Project were included in the analyses. The 2MWT performance result was used as a proxy for cardiovascular endurance. Fluid and crystalized composite neurocognitive scores were used to assess cognition. Resting-state functional MRI data were processed to measure hippocampal FC. Linear regression was used to examine the association between 2MWT, hippocampal FC, and neurocognitive outcomes after controlling for age, sex, years of education, body mass index, systolic blood pressure, and gait speed. RESULTS: Better 2MWT performance was associated with greater FC between the anterior hippocampus and right posterior cingulate and left middle temporal gyrus. No associations between 2MWT and posterior hippocampal FC, whole hippocampal FC, and caudate FC (control region) were observed. Greater anterior hippocampal FC was associated with better crystalized cognition scores. Lastly, greater FC between the anterior hippocampus and right posterior cingulate mediated the association between better 2MWT scores and higher crystalized cognition scores. CONCLUSIONS: Anterior hippocampal FC may be one underlying neurophysiological mechanism that promotes the association between 2MWT performance and crystalized composite cognitive function in healthy young adults.

Acute cycling exercise and hippocampal subfield function and microstructure in healthy older adults.

Aging is associated with deterioration in dentate gyrus (DG) and CA3, both crucial hippocampal subfields for age susceptible memory processes such as mnemonic discrimination (MD). Meanwhile, a single aerobic exercise session alters DG/CA3 function and neural activity in both rats and younger adults and can elicit short-term microstructural alterations in the hippocampus of older adults. However, our understanding of the effects of acute exercise on hippocampal subfield integrity via function and microstructure in older adults is limited. Thus, a within subject-design was employed to determine if 20-min of moderate to vigorous aerobic exercise alters bilateral hippocampal subfield function and microstructure using high-resolution functional magnetic resonance imaging (fMRI) during an MD task (n = 35) and high angular resolution multi-shell diffusion imaging (n = 31), in healthy older adults, compared to seated rest. Following the exercise condition, participants exhibited poorer MD performance, particularly when their perception of effort was higher. Exercise was also related to lower MD-related activity within the DG/CA3 but not CA1 subfield. Finally, after controlling for whole brain gray matter diffusion, exercise was associated with lower neurite density index (NDI) within the DG/CA3. However, exercise-related differences in DG/CA3 activity and NDI were not associated with differences in MD performance. Our results suggest moderate to vigorous aerobic exercise may temporarily inhibit MD performance, and suppress DG/CA3 MD-related activity and NDI, potentially through neuroinflammatory/glial processes. However, additional studies are needed to confirm whether these short-term changes in behavior and hippocampal subfield neurophysiology are beneficial and how they might relate to long-term exercise habits.

Emotional processing and positive affect after acute exercise in healthy older adults.

The well-elucidated improvement of mood immediately after exercise in older adults presumably involves adaptations in emotion-processing brain networks. However, little is known about effects of acute exercise on appetitive and aversive emotion-related network recruitment in older adults. The purpose of this study was to determine the effect of acute exercise, compared to a seated rest control condition, on pleasant and unpleasant emotion-related regional activation in healthy older adults. Functional MRI data were acquired from 32 active older adults during blocked presentations of pleasant, neutral and unpleasant images from the International Affective Pictures System. fMRI data were collected after participants completed 30 min of moderate to vigorous intensity cycling or seated rest, performed in a counterbalanced order across separate days in a within-subject design. The findings suggest three ways that emotional processing in the brain may be different immediately after exercise (relative to immediately after rest): First, reduced demands on emotional regulation during pleasant emotional processing as indicated by lower precuneus activation for pleasant stimuli; second, reduced processing of negative emotional stimuli in visual association areas as indicated by lower activation for unpleasant stimuli in the bilateral fusiform and ITG; third, an increased recruitment in activation associated with regulating/inhibiting unpleasant emotional processing in the bilateral medial superior frontal gyrus (dorsomedial prefrontal cortex), angular gyri, supramarginal gyri, left cerebellar crus I/II and a portion of right dorsolateral prefrontal cortex. Overall, these findings support that acute exercise in active older adults alters activation in key emotional processing and regulating brain regions.

Physical fitness, cognition, and structural network efficiency of brain connections across the lifespan.

Inadequate levels of exercise is one of the most potent modifiable risk factors for preventing cognitive decline and dementia as we age. Meanwhile, network science-based measures of structural brain network global and local efficiency show promise as robust biomarkers of aging, cognitive decline, and pathological disease progression. Despite this, little to no work has established how maintaining physical activity (PA) and physical fitness might relate to cognition and network efficiency measures across the lifespan. Therefore the purpose of this study was to determine the relationship between (1) PA and fitness and cognition, (2) fitness and network efficiency, and (3) how network efficiency measures relate to cognition. To accomplish this, we analyzed a large cross-sectional data set (n = 720; 36-100 years) from the aging human connectome project, which included the Trail Making Task (TMT) A and B, a measure of fitness (2-min walk test), physical activity (International Physical Activity Questionnaire), and high-resolution diffusion imaging data. Our analysis consisted of employing multiple linear regression while controlling for age, sex, and education. Age was associated with lower global and local brain network efficiency and poorer Trail A & B performance. Meanwhile, fitness, but not physical activity, was related to better Trail A and B performance and fitness, and was positively associated with local and global brain efficiency. Finally, local efficiency was related to better TMT B performance and partially mediated the relationship between fitness and TMT B performance. These results indicate aging may be associated with a shift towards less efficient local and global neural networks and that maintaining physical fitness might protect against age-related cognitive performance deterioration by bolstering structural network efficiency.

Effects of acute aerobic exercise on mnemonic discrimination performance in older adults.

OBJECTIVES: Ample evidence suggests exercise is beneficial for hippocampal function. Furthermore, a single session of aerobic exercise provides immediate benefits to mnemonic discrimination performance, a highly hippocampal-specific memory process, in healthy younger adults. However, it is unknown if a single session of aerobic exercise alters mnemonic discrimination in older adults, who generally exhibit greater hippocampal deterioration and deficits in mnemonic discrimination performance. METHODS: We conducted a within subject acute exercise study in 30 cognitively healthy and physically active older adults who underwent baseline testing and then completed two experimental visits in which they performed a mnemonic discrimination task before and after either 30 min of cycling exercise or 30 min of seated rest. Linear mixed-effects analyses were conducted in which condition order and age were controlled, time (pre vs. post) and condition (exercise vs. rest) were modeled as fixed effects, and subject as a random effect. RESULTS: No significant time by condition interaction effect was found for object recognition (p = .254, η2=.01), while a significant reduction in interference was found for mnemonic discrimination performance following the exercise condition (p = .012, η2=.07). A post-intervention only analysis indicated that there was no difference between condition for object recognition (p = .186, η2=.06), but that participants had better mnemonic discrimination performance (p < .001, η2=.22) following the exercise. CONCLUSIONS: Our results suggest a single session of moderate-intensity aerobic exercise may reduce interference and elicit better mnemonic discrimination performance in healthy older adults, suggesting benefits for hippocampal-specific memory function.

Mean arterial pressure, fitness, and executive function in middle age and older adults.

Previous literature suggests that higher fitness is related to better executive function in older adulthood, but the mechanisms underlying this association are poorly understood. While many studies have focused on these associations in older adulthood, recent evidence suggests the importance of cardiorespiratory fitness (CRF) and long-term blood pressure control on cognitive functioning. The purpose of the current study was to examine whether mean arterial pressure (MAP) mediated the association between CRF and executive function in middle age and older adults. Participants were adults (age 40+) without any self-reported psychiatric and neurological disorders or cognitive impairment from the Nathan Kline Institute Rockland Sample (N = 224, M age = 56). CRF was defined by V̇O2max estimated via a bike test, neuropsychological testing was used to examine executive functioning, and MAP was calculated from systolic and diastolic blood pressure recordings. Mediation models were analyzed controlling for age, sex, and education. Results indicated that higher CRF was associated with better inhibition (B = -0.0048, t = -2.16, p = 0.03) and there was a significant indirect effect of greater CRF on better inhibition through lower MAP (B = -0.0011; CI [-0.0026, -0.0002]). There were additional significant indirect effects of greater CRF and better fluency (B = 0.0028; CI [.0009, 0.0053]) and planning (B = 0.0037; CI [.0014, 0.0074]) through lower MAP. This suggests that MAP may be an underlaying physiological mechanism by which CRF influences executive function in mid- and older adulthood.

Associations between cardiorespiratory fitness, monocyte polarization, and exercise-related changes in mnemonic discrimination performance in older adults.

Biological aging is accompanied by a chronic pro-inflammatory state that may facilitate losses in hippocampal-dependent mnemonic discrimination. Aerobic exercise training promotes adaptations that include improved immune competency, higher cardiorespiratory fitness, and maintenance of hippocampal function. However, it is poorly understood whether, in active older adults, baseline immune cell profiles and cardiorespiratory fitness are possible mechanisms that facilitate the long-term benefits to hippocampal dependent mnemonic discrimination performance. This within-subjects study with counterbalanced conditions aimed to investigate whether baseline monocyte polarization and cardiorespiratory fitness influenced performance in the mnemonic similarity task (MST) and related Lure Discrimination Index (LDI) score after an acute bout of exercise. Twenty-one active older adults (M = 68 ± 5 yrs) underwent baseline testing in which blood samples were collected and cardiorespiratory fitness measured. Participants then returned and completed a seated rest or moderate intensity aerobic exercise condition in which the MST was proctored prior to and 5 min after each condition. A linear mixed effects model was used in which Participant ID was a random effect and Condition (rest v. exercise), Time (pre- v post-), and order were fixed main effects. Simple linear regression models were used to determine the variance accounted for by monocyte phenotypes and cardiorespiratory fitness for LDI scores post-condition. Post-rest LDI scores were significantly lower than post-exercise LDI scores (t(20) = -2.65, p < 0.02, d = -0.57). Intermediate monocytes were significant predictors of the change in pre- to post-exercise LDI scores (F(1, 19) = 6.03, p = 0.024, R2 = 0.24) and cardiorespiratory fitness was a significant predictor of the difference between post-condition LDI scores (F(1, 19) = 6.71, p = 0.018, R2 = 0.26). Our results suggest baseline cardiorespiratory fitness and intermediate monocytes may relate to the integrity of hippocampal-dependent mnemonic discrimination performance, and possibly the degree of responsiveness to aerobic exercise interventions.

Neurite dispersion and density mediates the relationship between cardiorespiratory fitness and cognition in healthy younger adults.

Growing evidence suggests physical activity and cardiorespiratory fitness are associated with better cognition across the lifespan. However, the neurobiological underpinnings relating fitness and cognition remain unclear, particularly in healthy younger adults. Using a well-established and popular multi-compartment diffusion modeling approach, called Neurite Orientation and Dispersion and Density Imaging (NODDI), we investigated the relationship between physical fitness (measured via a 2-min walk test), cognition (fluid and crystallized), and gray and white matter microstructure, in a large sample (n = 816) of healthy younger adults (ages 22-35 years) from the human connectome project (HCP). Concurrent with previous literature, we found that fitness was positively associated with both fluid and crystallized cognition. Furthermore, we found that physical fitness was negatively associated with white matter orientation dispersion index (ODIWM) around the cerebellar peduncle and was negatively associated with widespread cortical and subcortical gray matter neurite density index (NDIGM). Lower ODIWM of the cerebral peduncle was associated with better fluid cognitive performance, while lower NDIGM was associated with better crystallized cognition. Finally, we found that while ODIWM partially mediated the relationship between fitness and fluid cognition, NDIGM partially mediated the relationship between fitness and crystallized cognition. This study is the first to explore the relationship between physical fitness and white and gray matter microstructure measures using NODDI. Our findings suggest that in addition to improved cognitive performance, higher physical fitness may be associated with lower white matter tract dispersion and lower neurite density in the cortical and subcortical gray matter of healthy younger adults.

Differential associations of regional cerebellar volume with gait speed and working memory.

The relationship between gait speed and working memory is well-understood in older adults. However, it remains to be determined whether this relationship also exists in younger adults; and there is little known regarding the possible neural mechanism underlying the association between gait speed and working memory. The aims of this study are to determine if there is: (1) an association between gait speed and working memory performance; and (2) a mediating role of cerebellar subregion volume in the correlation between gait speed and working memory in healthy younger adults. 1054 younger adults (28.7 ± 3.6 years) from the Human Connectome Project were included in the analyses. A four-meter gait test was used to assess gait speed. The 2-back task was used to measure working memory performance [accuracy and response time (RT)]. T1-weighted structural MRI data (obtained using Siemens 3 T MRI scanner) was used to assess cerebellar subregion volumes. Linear regression and mediation analysis were used to examine the relationships between the variables after controlling for age, sex, and education. There was no association between gait speed and 2-back working memory performance in younger adults. Greater Crus I and whole cerebellar volumes were associated with better 2-back working memory accuracy. Greater VIIIa volume was associated with faster gait speed. Greater Crus 1 and VIIIa volumes were also associated with higher fluid cognition. The present study suggests that specific subregions of the cerebellar volumes are distinctively associated with gait speed and working memory performance in healthy younger adults.

Forward-focused coping predicts better mental health outcomes in mid- to late-life during the COVID-19 pandemic.

Objectives: Psychosocial stressors associated with the COVID-19 pandemic may increase the risk of depression and anxiety in the general population. Individuals approaching or within older adulthood may be especially vulnerable to these psychosocial stressors and their impact on mental health outcomes. Consequently, there is an urgent need to identify protective factors for older adults. The purpose of the present study was to determine the relative contribution of coping flexibility (CF) and two distinct coping strategies, forward-focused and trauma-focused, on negative affect in persons 50 years of age and older during the COVID-19 pandemic. Method: Data were collected using an online survey, including questions about demographic information, coping, depression, and anxiety. Participants aged 50 and over were included in our analyses of depression (N = 800) and anxiety (N = 638). Results: Both higher CF and higher forward-focused coping predicted lower depression and lower anxiety. In contrast, higher trauma-focused coping predicted slightly higher depressive symptoms but was not a significant predictor of anxiety. Conclusion: Our findings suggest that higher forward-focused coping may serve as a protective factor in older adults during the pandemic and, therefore, may be an effective treatment target for mental health interventions.

Evidence for exercise-related plasticity in functional and structural neural network connectivity.

The number of studies investigating exercise and cardiorespiratory fitness (CRF)-related changes in the functional and structural organization of brain networks continues to rise. Functional and structural connectivity are critical biomarkers for brain health and many exercise-related benefits on the brain are better represented by network dynamics. Here, we reviewed the neuroimaging literature to better understand how exercise or CRF may facilitate and maintain the efficiency and integrity of functional and structural aspects of brain networks in both younger and older adults. Converging evidence suggests that increased exercise performance and CRF modulate functional connectivity of the brain in a way that corresponds to behavioral changes such as cognitive and motor performance improvements. Similarly, greater physical activity levels and CRF are associated with better cognitive and motor function, which may be brought about by enhanced structural network integrity. This review will provide a comprehensive understanding of trends in exercise-network studies as well as future directions based on the gaps in knowledge that are currently present in the literature.

Hippocampal Functional Connectivity and Memory Performance After Exercise Intervention in Older Adults with Mild Cognitive Impairment.

BACKGROUND: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction. OBJECTIVE: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance). METHODS: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression. RESULTS: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants. CONCLUSION: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.

Older Adults' Behavior Intentions Once a COVID-19 Vaccine Becomes Available.

BACKGROUND: The purpose of this study was to examine the impact of antecedent variables on older adults' intention to get a CORONAVIRUS DISEASE-2019 vaccine. Older adults are at higher risk of severe illness from the disease and face an increasingly ageist general population who misrepresent the pandemic as an older adult problem. We use the Theory of Planned Behavior framework to examine vaccine behavior intention. METHOD: A convenience sample (n = 583) of adults aged 60 and older in the United States participated in an online survey using vignettes. Hierarchical regression and analysis of covariance were used to test our model. RESULTS: Results suggest that perceived risk of the pandemic, general vaccine beliefs, and political affiliation influence respondents' attitude toward the vaccine. Respondents' attitudes toward the vaccine and their physician's recommendation help shape vaccine intention. CONCLUSION: The results provide partial support to the proposed model in shaping vaccine intention among older adults.

Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.

Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise.

INTRODUCTION: The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural magnetic resonance imaging. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise. METHODS: We used a within-subject design to determine if a 30-min bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging measures in healthy older adults (n = 30) compared with a seated rest control condition. RESULTS: Significantly lower fractional anisotropy and higher mean diffusivity were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity. No significant differences in axial diffusivity were observed. CONCLUSIONS: These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.