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. Yet, 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-minute walk test (2MWT), while subjective sleep quality was measured with the continuous Pittsburgh Sleep Quality Index (PSQI) 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 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.

Brain-wide functional connectome analysis of 40,000 individuals reveals brain networks that show aging effects in older adults.

The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.

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.

Moderate-to-vigorous intensity cycling exercise immediately after visual learning enhances delayed recognition memory performance.

A single bout of acute aerobic exercise has been shown to improve long-term memory, though it is unclear if exercise before learning or after learning is optimal for memory enhancement. Although some research has demonstrated that exercise before learning is ideal, investigations have consistently shown that acute arousal post-learning is a powerful memory enhancer. Therefore, the purpose of this investigation was to compare the effects of self-perceived hard cycling before or after learning on recognition memory for emotional and neutral images, and examine the relationship between central noradrenergic activity and memory performance. Seventy-two males and females (18-35 years of age) participated in this between-subjects study. Participants were randomly assigned to one of the following groups: exercise before learning, exercise after learning, and control. Participants in the exercise groups engaged in 20 min of cycling at a rating of perceived exertion (RPE) of 15 ("hard") on the Borg RPE scale before or after viewing a series of 90 pleasant, unpleasant, and neutral images (30 each). Participants in the control group engaged in no exercise before or after image viewing. At several time points throughout the experiment, saliva was collected to measure salivary alpha amylase (sAA), a marker of central noradrenergic activity. One-week later, recognition memory was assessed where participants viewed 180 images (90 new) and had to identify which images were previously viewed. Participants in the exercise after learning group had significantly higher recognition memory compared to the control group, but this was not seen with exercise before learning. sAA was not correlated with memory in any group, though it did increase during exercise. These results demonstrate that acute self-perceived hard cycling post-learning, but not pre-learning, improves recognition memory, though this was unrelated to the exercise-induced increase in central noradrenergic activity as measured in saliva.

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.

Basal forebrain functional connectivity as a mediator of associations between cardiorespiratory fitness and cognition in healthy older women.

Age-related cholinergic dysfunction within the basal forebrain (BF) is one of the key hallmarks for age-related cognitive decline. Given that higher cardiorespiratory fitness (CRF) induces neuroprotective effects that may differ by sex, we investigated the moderating effects of sex on the associations between CRF, BF cholinergic function, and cognitive function in older adults. 176 older adults (68.5 years) were included from the Nathan Kline Institute Rockland Sample. Functional connectivity (rsFC) of the BF subregions including the medial septal nucleus/diagonal band of Broca (MS/DB) and nucleus basalis of Meynert (NBM) were computed from resting-sate functional MRI. Modified Astrand-Ryhming submaximal cycle ergometer protocol was used to estimate CRF. Trail making task and inhibition performance during the color word interference test from the Delis-Kaplan Executive Function System and Rey Auditory Verbal Learning Test were used to examine cognitive function. Linear regression models were used to assess the associations between CRF, BF rsFC, and cognitive performance after controlling for age, sex, and years of education. Subsequently, we measured the associations between the variables in men and women separately to investigate the sex differences. There was an association between higher CRF and greater rsFC between the NBM and right middle frontal gyrus in older men and women. There were significant associations between CRF, NBM rsFC, and trail making task number-letter switching performance only in women. In women, greater NBM rsFC mediated the association between higher CRF and better trail making task number-letter switching performance. These findings provide evidence that greater NBM rsFC, particularly in older women, may be an underlying neural mechanism for the relationship between higher CRF and better executive function.

Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment.

Background: Despite growing evidence regarding the association between exercise training (ET) and functional brain network connectivity, little is known about the effects of ET on large-scale within- and between-network functional connectivity (FC) of core brain networks. Objective: We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). The association between ET-induced changes in FC and cognitive performance was examined. Methods: 33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in this study. Before and after a 12-week walking ET intervention, participants underwent a graded exercise test, Controlled Oral Word Association Test (COWAT), Rey Auditory Verbal Learning Test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within (W) and between (B) network connectivity of the DMN, FPN, and SAL. We used linear regression to examine associations between ET-related changes in network connectivity and cognitive function. Results: There were significant improvements in cardiorespiratory fitness, COWAT, RAVLT, and LM after ET across participants. Significant increases in DMNW and SALW, and DMN-FPNB, DMN-SALB, and FPN-SALB were observed after ET. Greater SALW and FPN-SALB were associated with enhanced LM immediate recall performance after ET in both groups. Conclusion: Increased within- and between-network connectivity following ET may subserve improvements in memory performance in older individuals with intact cognition and with MCI due to Alzheimer's disease.

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.

The Effects of Acute Resistance Exercise on Memory, Processing Speed, and Mood State After a Cognitive Challenge.

ABSTRACT: Venezia, AC, Barney, P, Spagnoli, D, Greco-Hiranaka, C, Piepmeier, AT, Smith, JC, and Weiss, LR. The effects of acute resistance exercise on memory, processing speed, and mood state after a cognitive challenge. J Strength Cond Res 37(9): 1738-1745, 2023-Acute moderate-to-vigorous-intensity aerobic exercise has been shown to improve learning and memory, but the effectiveness of acute high-intensity resistance exercise for improving memory is not fully understood. Like acute aerobic exercise, acute resistance exercise increases arousal and circulating catecholamines, mechanisms suggested to mediate the memory-enhancing effects of acute exercise. Furthermore, although acute exercise has been shown to benefit mood state, it is unknown if high-intensity resistance exercise positively influences mood state after a cognitive challenge. In this within-subjects design, subjects (18- to 25-year-old men) completed an approximately 40-minute session of resistance exercise or seated rest. Immediately after, the Automated Neuropsychological Assessment Metrics (ANAM) Code Substitution (CS)-Learning, CS-Immediate Recognition, and CS-Delayed Recognition tasks were completed, followed by the ANAM Mood Scale. There were no significant effects of exercise on recognition memory; however, CS-Learning (attention and processing speed) was better after resistance exercise ( p = 0.03). After the cognitive challenge, restlessness ( p < 0.001), vigor ( p = 0.03), and depression ( p = 0.047) scores were higher after resistance exercise compared with rest; however, after false discovery rate correction, only restlessness remained significantly different between sessions ( q = 0.002), whereas vigor ( q = 0.09) and depression ( q = 0.09) did not. These results suggest that an acute bout of resistance exercise improves attention and processing speed, although it does not improve recognition memory and has mixed effects on mood state in college-aged men.

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.

Cardiorespiratory Fitness as a Moderator of Sleep-Related Associations with Hippocampal Volume and Cognition.

The objective of this study was to understand the associations of sleep and cardiorespiratory fitness with hippocampal volume and global cognition among older adults (n = 30, age = 65.8 years, female = 73.3%). Wrist actigraphy provided objective measures of nighttime sleep including sleep duration, average wake bout length (WBL; sleep disturbance), and wake-to-sleep transition probability (WTSP; sleep consolidation). Cardiorespiratory fitness was quantified via cycle exercise using a modified heart rate recovery approach. Magnetic resonance imaging was used to determine hippocampal volume and the Mini-Mental State Examination was used to assess global cognition. Fitness moderated associations of sleep with hippocampal volume and cognitive performance, whereby the association of WBL-an index of poor sleep-with hippocampal atrophy was stronger among less-fit individuals, and the association of sleep duration with cognitive performance was stronger among more-fit individuals. Across the fitness levels, a longer WBL was associated with lower cognitive performance, and a higher WTSP-an index of more consolidated sleep-was associated with greater hippocampal volume. Sleep and fitness were unrelated to the volume of an amygdala control region, suggesting a degree of neuroanatomical specificity. In conclusion, higher cardiorespiratory fitness may attenuate sleep disturbance-related hippocampal atrophy and magnify the cognitive benefits of good sleep. Prospective studies are needed to confirm these findings.

Subjective Well-Being and Bilateral Anterior Insula Functional Connectivity After Exercise Intervention in Older Adults With Mild Cognitive Impairment.

While it is well known that exercise training is associated with improvement in subjective well-being among older adults, it is unclear if individuals with cognitive impairment experience the same effects elicited by exercise on subjective well-being. We further explored whether the bilateral anterior insula network may be an underlying neural mechanism for the exercise training-related improvements in subjective well-being. We investigated the effects of exercise training on subjective well-being in older adults (78.4 ± 7.1 years) with mild cognitive impairment (MCI; n = 14) and a cognitively normal (CN; n = 14) control group. We specifically assessed the relationship between changes in subjective well-being and changes in functional connectivity (FC) with the bilateral anterior insula from before to after exercise training. Cardiorespiratory fitness, subjective well-being, and resting-state fMRI were measured before and after a 12-week moderate-intensity walking intervention. A seed-based correlation analysis was conducted using the bilateral anterior insula as a priori seed regions of interest. The associations between bilateral anterior insula FC with other brain regions and subjective well-being were computed before and after exercise training, respectively, and the statistical difference between the correlations (before vs after exercise training) was evaluated. There was a significant Group (MCI vs CN) × Time (before vs after exercise training) interaction for subjective well-being, such that while those with MCI demonstrated significantly increased subjective well-being after exercise training, no changes in subjective well-being were observed in CN. Participants with MCI also showed an exercise training-related increase in the bilateral anterior insula FC. While there was no significant correlation between subjective well-being and bilateral anterior insula FC before exercise training, a positive association between subjective well-being and bilateral anterior insula FC was found in the MCI group after exercise training. Our findings indicate that 12 weeks of exercise training may enhance subjective well-being in older adults diagnosed with MCI and, further, suggest that increased bilateral anterior insula FC with other cortical regions may reflect neural network plasticity associated with exercise training-related improvements in subjective well-being.

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.

Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'.

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.