Increased neural differentiation after a single session of aerobic exercise in older adults.

Aging is associated with decreased cognitive function. One theory posits that this decline is in part due to multiple neural systems becoming dedifferentiated in older adults. Exercise is known to improve cognition in older adults, even after only a single session. We hypothesized that one mechanism of improvement is a redifferentiation of neural systems. We used a within-participant, cross-over design involving 2 sessions: either 30 minutes of aerobic exercise or 30 minutes of seated rest (n = 32; ages 55-81 years). Both functional Magnetic Resonance Imaging (fMRI) and Stroop performance were acquired soon after exercise and rest. We quantified neural differentiation via general heterogeneity regression. There were 3 prominent findings following the exercise. First, participants were better at reducing Stroop interference. Second, while there was greater neural differentiation within the hippocampal formation and cerebellum, there was lower neural differentiation within frontal cortices. Third, this greater neural differentiation in the cerebellum and temporal lobe was more pronounced in the older ages. These data suggest that exercise can induce greater neural differentiation in healthy aging.

Integrating sleep health into resilience research.

Sleep is a biological necessity that is a critical determinant of mental and physical well-being. Sleep may promote resilience by enhancing an individual's biological preparedness to resist, adapt and recover from a challenge or stressor. This report analyzes currently active National Institutes of Health (NIH) grants focussed on sleep and resilience, specifically examining the design of studies that explore sleep as a factor that promotes health maintenance, survivorship, or protective/preventive pathways. A search of NIH R01 and R21 research project grants that received funding in Fiscal Years (FY) 2016-2021 and focussed on sleep and resilience was conducted. A total of 16 active grants from six NIH institutes met the inclusion criteria. Most grants were funded in FY 2021 (68.8%), used the R01 mechanism (81.3%), were observational studies (75.0%), and measured resilience in the context of resisting a stressor/challenge (56.3%). Early adulthood and midlife were most commonly studied and over half of the grants focussed on underserved/underrepresented populations. NIH-funded studies focussed on sleep and resilience, or the ways in which sleep can influence an individual's ability to resist, adapt, or recover from a challenging event. This analysis highlights an important gap and the need to expand research focussed on sleep as a promotor of molecular, physiological, and psychological resilience.

Associations of circadian rest/activity rhythms with cognition in middle-aged and older adults: Demographic and genetic interactions.

Objectives: Wrist actigraphs (accelerometers) can record motor activity over multiple days and nights. The resulting data can be used to quantify 24-h activity profiles, known as circadian rest-activity rhythms (CRARs). Actigraphic CRARs have been tied to cognitive performance and decline in older adults; however, little is known about links between CRARs and performance or change in specific cognitive domains, or how individual differences may influence these associations. We investigated associations of actigraphic CRARs with cognitive performance and change in middle-aged and older adults, and explored whether age, sex/gender, race, and apolipoprotein E (APOE) e4 carrier status moderated these associations. Materials and methods: Participants (N = 422; 47% male) were cognitively healthy adults (i.e., without mild cognitive impairment or dementia) at baseline aged ≥ 50 years from the Baltimore Longitudinal Study of Aging who completed 5.6 ± 0.89 nights of wrist actigraphy and tests of memory, executive function, attention, language, and visuospatial ability at the same visit the actigraph was issued; 292 participants had repeat cognitive testing 3.12 (1.58) years later. Predictors included indices of rhythm strength [i.e., amplitude; relative amplitude (RA); interdaily stability (IS); mesor], delayed timing of the rhythm peak [i.e., later acrophase; midpoint of an individual's least active 5 h (L5 time); midpoint of an individual's most active 10 h (M10 time)], and fragmentation [i.e., intradaily variability (IV)]. Results: In main effects, later L5 time was cross sectionally associated with poorer memory, and greater IS predicted slower longitudinal memory decline. Associations of CRARs with cognition differed as a function of age, sex/gender, race, and APOE e4 carrier status. Conclusion: Among middle-aged and older adults, delayed circadian phase is associated with poorer memory performance, and greater day-to-day rhythm stability is associated with slower declines in memory. Significant interactions suggest that CRARs are generally more strongly associated with cognitive performance and rate of cognitive decline among women, Black adults, older individuals, and APOE e4 carriers. Replication in independent samples is needed.

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.

Actigraphy-estimated physical activity is associated with functional and structural brain connectivity among older adults.

Higher physical activity levels are associated with reduced cognitive decline among older adults; however, current understanding of underlying brain mechanisms is limited. This cross-sectional study investigated the relationship between actigraphy-estimated total volume of physical activity (TVPA) and magnetic resonance imaging (MRI) measures of white matter hyperintensities (WMH), and functional and structural brain connectivity, measured by resting-state functional MRI and diffusion tensor imaging. Study participants (N = 156, mean age = 71 years) included 136 with normal cognition and 20 with Mild Cognitive Impairment. Higher TVPA was associated with greater functional connectivity within the default-mode network and greater network modularity (a measure of network specialization), as well as with greater anisotropy and lower radial diffusion in white matter, suggesting better structural connectivity. These associations with functional and structural connectivity were independent of one another and independent of the level of vascular risk, APOE-ε4 status, cognitive reserve, and WMH volume, which were not associated with TVPA. Findings suggest that physical activity is beneficial for brain connectivity among older individuals with varying levels of risk for cognitive decline.

Associations of actigraphic sleep and circadian rest/activity rhythms with cognition in the early phase of Alzheimer's disease.

STUDY OBJECTIVES: To compare sleep and circadian rest/activity rhythms (RARs), quantified by standard and novel actigraphic metrics, between controls and participants with mild cognitive impairment (MCI), and to examine the cross-sectional relationships between these measures and cognition. METHODS: Actigraphy data were collected in 179 older individuals (mean age = 72.6 years) with normal cognition (n = 153) and MCI (n = 26). Sleep parameters (e.g. sleep efficiency), and standard nonparametric RARs (e.g. interdaily stability) were generated. Functional principal component analysis (fPCA) was used to generate three novel RAR metrics (fPC1, fPC2, and fPC3). Cognitive composite scores reflecting episodic memory and executive function were derived using factor analysis. Regression models compared sleep and RAR parameters between diagnostic groups and their association with cognitive performance. RESULTS: Compared to controls, the MCI group exhibited lower levels of the standard RAR parameter: relative amplitude and fPC3-a novel RAR whereby lower scores reflected a lower rhythm peak, as well as greater nighttime activity and less activity in the morning. Across groups, several standard RAR parameters (e.g. interdaily stability) and fPC3 were associated with better episodic memory and executive function performance. Additionally, several standard RAR measures (e.g. relative amplitude) and the novel RAR measure fPC1 (reflecting the total volume of activity and rhythm strength) were associated with better executive function performance. CONCLUSIONS: Individuals with MCI have altered circadian RARs compared to controls, including the novel RAR metric fPC3, reflecting greater nighttime activity and less activity in the morning compared to mean values. Additionally, these measures are significantly associated with cognitive performance.

Cardiovascular Endurance Modifies the Link between Subjective Sleep Quality and Entorhinal Cortex Thickness in Younger Adults.

INTRODUCTION: Poor sleep is linked to impaired cognitive function, cortical brain atrophy, and lower cortical thickness. Independently, higher cardiovascular endurance has neuroprotective effects. It remains in question, however, whether cardiovascular endurance moderates the relationship between sleep and brain health. The aims of this study included the following: 1) the association between subjective sleep quality and cognitive performance, hippocampus volume, and entorhinal cortex (EC) thickness, and 2) the moderating effects of cardiovascular endurance on the associations of sleep quality with cognitive and magnetic resonance imaging measures in healthy younger adults. METHODS: A total of 1095 younger adults (28.8 ± 3.6 yr) from the Human Connectome Project were included in the analyses. The 2-min walk test was used as a proxy of cardiovascular endurance. Self-reported sleep quality was measured using the Pittsburgh Sleep Quality Index. Composite cognitive tests were used to assess global cognition, and T1-weighted structural magnetic resonance imaging data (obtained using Siemens 3T scanner) was used to assess hippocampus volume and EC thickness. Linear regression was used to examine the moderating effects of fitness on the relationships between sleep and each of these neurocognitive outcomes after controlling for age, sex, and education year. RESULTS: Poorer sleep quality was associated with both a lower crystalized intelligence score (B = -0.198, P = 0.034) and lower EC thickness (B = -0.013, P = 0.003). With greater 2-min walk test score, the association between greater Pittsburgh Sleep Quality Index score and lower EC thickness was attenuated (B = 0.0008, P = 0.028). CONCLUSIONS: Higher cardiovascular endurance may mitigate the relationship between poorer subjective sleep quality and lower EC thickness. Future longitudinal studies should examine the interactive effects of sleep and fitness on brain health among older and more vulnerable populations.

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.

Association of objectively measured sleep with frailty and 5-year mortality in community-dwelling older adults.

STUDY OBJECTIVES: To determine whether actigraphy-measured sleep was independently associated with risk of frailty and mortality over a 5-year period among older adults. METHODS: We used data from Waves 2 (W2) and 3 (W3) (2010-2015) of the National Social Life, Health and Aging Project, a prospective cohort of community-dwelling older adults born between 1920 and 1947. One-third of W2 respondents were randomly selected to participate in a sleep study, of whom N = 727 consented and N = 615 were included in the analytic sample. Participants were instructed to wear a wrist actigraph for 72 h (2.93 ± 0.01 nights). Actigraphic sleep parameters were averaged across nights and included total sleep time, percent sleep, sleep fragmentation index, and wake after sleep onset. Subjective sleep was collected via questionnaire. Frailty was assessed using modified Fried Frailty Index. Vital status was ascertained at the time of the W3 interview. W3 frailty/mortality status was analyzed jointly with a four-level variable: robust, pre-frail, frail, and deceased. Associations were modeled per 10-unit increase. RESULTS: After controlling for baseline frailty (robust and pre-frail categories), age, sex, education, body mass index, and sleep time preference, a higher sleep fragmentation index was associated with frailty (OR = 1.70, 95% CI: 1.02-2.84) and mortality (OR = 2.12, 95% CI: 1.09-4.09). Greater wake after sleep onset (OR = 1.24, 95% CI: 1.02-1.50) and lower percent sleep (OR = 0.41, 95% CI: 0.17-0.97) were associated with mortality. CONCLUSIONS: Among community-dwelling older adults, actigraphic sleep is associated with frailty and all-cause mortality over a 5-year period. Further investigation is warranted to elucidate the physiological mechanisms underlying these associations.

Changes in cerebral perfusion following a 12-month exercise and diet intervention.

Overweight and obesity may damage the cerebrovascular architecture, resulting in a significant reduction in cerebral blood flow. To date, there have been few randomized clinical trials (RCT) examining whether obesity-related reductions in cerebral blood flow could be modified by weight loss. Further, it is unknown whether the behavioral intervention strategy for weight loss (i.e., diet alone or diet combined with exercise) differentially influences cerebral blood flow in adults with overweight or obesity. The primary aim of this study was to determine whether a 12-month RCT of exercise and diet increases cerebral blood flow in 125 midlife (Mean age ± SD = 44.63 ± 8.36 years) adults with overweight and obesity. Further, we evaluated whether weight loss via diet combined with aerobic exercise has an added effect on changes in cerebral blood flow compared to weight loss via diet alone and whether there were regionally specific effects of the type of behavioral intervention on cerebral blood flow patterns. Consistent with our predictions, a 12-month diet and exercise program resulting in 10% weight loss increased cerebral blood flow. These effects were widespread and extended throughout frontal, parietal, and subcortical regions. Further, there was some regional specificity of effects for both diet-only and diet combined with exercise. Our results demonstrate that weight-related reductions in cerebral blood flow can be modified by 10% weight loss over the course of 12 months and that interventions involving exercise exposure may provide unique effects on cerebral blood flow compared to interventions involving only diet.

Greater Semantic Memory Activation After Exercise Training Cessation in Older Endurance-Trained Athletes.

PURPOSE: To examine the effects of a 10-day exercise-training cessation on semantic memory functional activation in older distance runners. METHODS: Ten master runners (62.6 ± 7.0 years) with a long-term endurance-training history (29.0 ± 6.0 years) underwent a 10-day training cessation. Before and immediately after the training cessation, semantic memory activation was measured during the famous name recognition task, using functional magnetic resonance imaging. RESULTS: The 10-day training cessation resulted in greater semantic memory activation in three brain regions, including the left inferior frontal gyrus, parahippocampal gyrus, and inferior semilunar lobule. The 10-day training cessation did not significantly alter famous name recognition task performance. CONCLUSIONS: The findings demonstrate that even a relatively short period without exercise training alters the functional activation patterns of semantic memory-related neural networks. Increased semantic memory activation after training cessation may indicate reduced neural efficiency during successful memory retrieval.

Impact of exercise on older adults' mood is moderated by sleep and mediated by altered brain connectivity.

Older adults comprise the fastest growing global demographic and are at increased risk of poor mental health outcomes. Although aerobic exercise and sleep are critical to the preservation of emotional well-being, few studies have examined their combined mood-enhancing effects, or the potential neural mechanisms underlying these effects. Here, we used a randomized crossover design to test the impact of acute exercise on mood and the intrinsic functional connectivity (iFC) of the cingulo-opercular network in physically healthy older adults. Wrist actigraphy provided objective indices of sleep. Results revealed that 30 min of moderate-intensity aerobic exercise acutely enhanced positive affect (PA) and reduced iFC between the cingulo-opercular network and the hippocampus. Both effects were magnified among older adults with greater sleep disturbance. Exercise-induced changes in hippocampal iFC mediated relations between sleep disturbance and exercise-induced increases in PA. These findings provide evidence that aerobic exercise enhances mood, that it does so by altering connectivity between the anterior insula-a key hub in the cingulo-opercular network-and the hippocampus and that lower sleep quality is a stronger predictor of these effects among older adults. These observations underscore the benefits of moderate-intensity exercise-a safe and scalable behavioral intervention-and provide new clues about the neural circuitry underlying the interactive effects of sleep and exercise on mood.

Associations of Actigraphic Sleep Parameters With Fatigability in Older Adults.

BACKGROUND: Poor sleep may increase the likelihood of fatigue, and both are common in later life. However, prior studies of the sleep-fatigue relationship used subjective measures or were conducted in clinical populations; thus, the nature of this association in healthier community-dwelling older adults remains unclear. We studied the association of actigraphic sleep parameters with perceived fatigability-fatigue in response to a standardized task-and with conventional fatigue symptoms of low energy or tiredness. METHODS: We studied 382 cognitively normal participants in the Baltimore Longitudinal Study of Aging (aged 73.1 ± 10.3 years, 53.1% women) who completed 6.7 ± 0.9 days of wrist actigraphy and a perceived fatigability assessment, including rating of perceived exertion (RPE) after a 5-minute treadmill walk or the Pittsburgh Fatigability Scale (PFS). Participants also reported non-standardized symptoms of fatigue. RESULTS: After adjustment for age, sex, race, height, weight, comorbidity index, and depressive symptoms, shorter total sleep time (TST; <6.3 hours vs intermediate TST ≥6.3 to 7.2 hours) was associated with high RPE fatigability (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.29, 5.06, p = .007), high PFS physical (OR = 1.88, 95% CI = 1.04, 3.38, p = .035), and high mental fatigability (OR = 2.15, 95% CI = 1.02, 4.50, p = .044), whereas longer TST was also associated with high mental fatigability (OR = 2.19, 95% CI = 1.02, 4.71, p = .043). Additionally, longer wake bout length was associated with high RPE fatigability (OR = 1.53, 95% CI = 1.14, 2.07, p = .005), and greater wake after sleep onset was associated with high mental fatigability (OR = 1.14, 95% CI = 1.01, 1.28, p = .036). CONCLUSION: Among well-functioning older adults, abnormal sleep duration and sleep fragmentation are associated with greater perceived fatigability.

Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults.

BACKGROUND: Systemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer's disease, but inflammation's effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the modifying role of cortical amyloid and APOE ε4 status. METHODS: Blood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 176 participants (at baseline mean age: 65 (SD 9) years; 63% women; 85% cognitively normal, 15% mild cognitive impairment (MCI)) and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 137 participants also underwent 11C Pittsburgh compound-B (PiB) PET imaging to assess cortical amyloid burden. RESULTS: Using linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with lower connectivity within the Default Mode (ß = -0.013; 95% CI: -0.023, -0.003) and the Dorsal Attention Networks (ß = -0.017; 95% CI: -0.028, -0.006). The strength of these associations did not vary by amyloid status (positive/negative). However, there was a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated lower connectivity. Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (Control, Limbic, and Salience/Ventral Attention networks). CONCLUSION: Peripheral pro-inflammatory signaling in older adults without dementia, especially among APOE ε4-positive individuals, is associated with altered connectivity within two large-scale cognitive networks.

Later-life sleep, cognition, and neuroimaging research: an update for 2020.

This review summarizes recent studies of sleep and brain health in later life, focusing on cognitive and magnetic resonance imaging (MRI)-derived outcomes. The majority of older people report sleep problems, and over one-third have sleep-disordered breathing (SDB). The research described herein builds on work demonstrating that abnormal sleep duration, sleep fragmentation, and SDB are associated with memory impairment and executive dysfunction. Self-reported short sleep is linked with greater cortical thinning and lower white matter integrity, and objectively measured fragmentation and SDB are tied to gray matter atrophy and altered connectivity. Results suggest that brain changes mediate previously identified sleep-cognition associations. Additional clinical trials are needed to determine whether treating insomnia or SDB benefits cognition in this population.

Brain activation during executive control after acute exercise in older adults.

Previous work has shown that aerobic exercise training is associated with regional changes in functional activation and improved behavioral outcomes during the Flanker task. However, it is unknown whether acute aerobic exercise has comparable effects on brain activation during the Flanker task. The aim of this study was to examine the effects of an acute bout of moderate-intensity bicycle exercise on Flanker task functional activation and behavioral performance in older adults. Thirty-two healthy older adults (66.2 ±â€¯7.3 years) performed two experimental visits that included 30-min of aerobic exercise and a rest condition on separate days. After each condition, participants performed the Flanker task during an fMRI scan. Significantly greater functional activation (incongruent > congruent) was found in the left inferior frontal gyrus and inferior parietal lobule after exercise compared to rest. A main effect of exercise was also observed on Flanker task performance with greater accuracy in both incongruent and congruent trials, suggesting the effects of acute exercise on Flanker performance are general across Flanker trial types. Conversely, greater executive control-related functional activations after performing a single session of exercise suggests enhanced functional processing while engaging in task conditions requiring disproportionately greater amounts of executive control.

Resting-State Functional Connectivity Is Associated With Cerebrospinal Fluid Levels of the Synaptic Protein NPTX2 in Non-demented Older Adults.

Intrinsic functional connectivity of large-scale brain networks has been shown to change with aging and Alzheimer's disease (AD). These alterations are thought to reflect changes in synaptic function, but the underlying biological mechanisms are poorly understood. This study examined whether Neuronal Pentraxin 2 (NPTX2), a synaptic protein that mediates homeostatic strengthening of inhibitory circuits to control cortical excitability, is associated with functional connectivity as measured by resting-state functional magnetic resonance imaging (rsfMRI) in five large-scale cognitive brain networks. In this cross-sectional study, rsfMRI scans were obtained from 130 older individuals (mean age = 69 years) with normal cognition (N = 113) and Mild Cognitive Impairment (N = 17); NPTX2 was measured in the same individuals in cerebrospinal fluid (CSF). Higher levels of NPTX2 in CSF were associated with greater functional connectivity in the salience/ventral attention network, based on linear regression analysis. Moreover, this association was stronger among individuals with lower levels of cognitive reserve, as measured by a composite score (comprised of years of education, reading, and vocabulary measures). Additionally, higher connectivity in the salience/ventral attention network was related to better performance on a composite measure of executive function. Levels of NPTX2 were not associated with connectivity in other networks (executive control, limbic, dorsal attention, and default-mode). Findings also confirmed prior reports that individuals with MCI have lower levels of NPTX2 compared to those with normal cognition. Taken together, the results suggest that NPTX2 mechanisms may play a central role among older individuals in connectivity within the salience/ventral attention network and for cognitive tasks that require modulation of attention and response selection.

Semantic Memory Activation After Acute Exercise in Healthy Older Adults.

OBJECTIVES: A growing body of research suggests that regular participation in long-term exercise is associated with enhanced cognitive function. However, less is known about the beneficial effects of acute exercise on semantic memory. This study investigated brain activation during a semantic memory task after a single session of exercise in healthy older adults using functional magnetic resonance imaging (fMRI). METHODS: Using a within-subjects counterbalanced design, 26 participants (ages, 55-85 years) underwent two experimental visits on separate days. During each visit, participants engaged in 30 min of rest or stationary cycling exercise immediately before performing a Famous and Non-Famous name discrimination task during fMRI scanning. RESULTS: Acute exercise was associated with significantly greater semantic memory activation (Famous>Non-Famous) in the middle frontal, inferior temporal, middle temporal, and fusiform gyri. A planned comparison additionally showed significantly greater activation in the bilateral hippocampus after exercise compared to rest. These effects were confined to correct trials, and as expected, there were no differences between conditions in response time or accuracy. CONCLUSIONS: Greater brain activation following a single session of exercise suggests that exercise may increase neural processes underlying semantic memory activation in healthy older adults. These effects were localized to the known semantic memory network, and thus do not appear to reflect a general or widespread increase in brain blood flow. Coupled with our prior exercise training effects on semantic memory-related activation, these data suggest the acute increase in neural activation after exercise may provide a stimulus for adaptation over repeated exercise sessions. (JINS, 2019, 25, 557-568).

Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment.

BACKGROUND: Exercise training has been associated with greater cerebral blood flow (CBF) in cognitively normal older adults (CN). Alterations in CBF, including compensatory perfusion in the prefrontal cortex, may facilitate changes to the brain's neural infrastructure. OBJECTIVE: To examine the effects of a 12-week aerobic exercise intervention on resting CBF and cognition in CN and those with mild cognitive impairment (MCI). We hypothesized individuals with MCI (versus CN) would exhibit greater whole brain CBF at baseline and that exercise would mitigate these differences. We also expected CBF changes to parallel cognitive improvements. METHODS: Before and after a 12-week exercise intervention, 18 CN and 17 MCI participants (aged 61-88) underwent aerobic fitness testing, neuropsychological assessment, and an MRI scan. Perfusion-weighted images were collected using a GE 3T MR system. Repeated measures analyses of covariance were used to test within- and between-group differences over time, followed by post-hoc analyses to examine links between CBF changes and cognitive improvement. RESULTS: At baseline, individuals with MCI (versus CN) exhibited significantly elevated perfusion in the left insula. Twelve weeks of aerobic exercise reversed this discrepancy. Additionally, exercise improved working memory (measured by the Rey Auditory Verbal Learning Test) and verbal fluency (measured by the Controlled Oral Word Association Test) and differentially altered CBF depending on cognitive status. Among those with MCI, decreased CBF in the left insula and anterior cingulate cortex was associated with improved verbal fluency. CONCLUSIONS: Exercise training alters CBF and improves cognitive performance in older adults with and without cognitive impairment. Future studies must evaluate the mediating effects of CBF on the association between exercise training and cognition.

Caudate Volume Mediates the Interaction between Total Sleep Time and Executive Function after Acute Exercise in Healthy Older Adults.

Although both exercise and sleep are significant lifestyle factors in cognitive aging, the interaction of these two factors with respect to cognition remains to be determined. Also, little is known regarding the role of the basal ganglia (BG) in cognitive aging despite its involvement in both sleep and executive function. The primary objective of this study was to investigate the interaction between sleep and acute exercise on executive function performance, and secondarily, to assess if BG volume mediates this interaction. Thirty healthy older adults (65.8±7.3 years) completed 30 minutes of seated rest or moderate-intensity cycling exercise on different days. Structural MRI was used to assess the volumes of BG components including caudate, putamen, and globus pallidus shortly after the experimental conditions. Approximately 90 minutes after each condition, the Stroop task was administered to measure executive function. To examine sleep, participants wore a wrist actigraph for 8.0±3.6 days prior to the first experimental session. Results revealed that while longer total sleep time (TST) was associated with shorter Stroop response time (RT), shorter TST was associated with longer RT after exercise, compared to rest, for both congruent (p = 0.029) and incongruent (p = 0.022) trials. Longer TST was correlated with greater caudate volume, and greater caudate volume was associated with exercise-related improvement in Stroop incongruent RT. Ultimately, we found that the association between longer sleep duration and faster processing speed after acute exercise was mediated by greater caudate volume. These findings suggest that TST is an important factor for acute exercise-induced cognitive improvements in older adults, and that our study is a first step in understanding the interactive effects of these important lifestyle factors in cognitive aging that might simultaneously be addressed to promote healthy cognitive aging. Future studies should examine the interactive effects of sleep and chronic exercise on cognitive function, and whether BG volume might also mediate this interaction.