A Compensatory Role of Physical Activity in the Association Between Sleep and Cognition.

We synthesize evidence investigating the hypothesis that greater engagement in physical activity (PA) may compensate for some of the negative cognitive consequences associated with poor sleep in older adults. Potential mechanistic pathways include glymphatic clearance, influences on depression, and other comorbidities. The evidence base is largely cross-sectional and observational, and further experimental studies are required.

Data-driven MRI analysis reveals fitness-related functional change in default mode network and cognition following an exercise intervention.

Previous research has indicated that cardiorespiratory fitness (CRF) is structurally and functionally neuroprotective in older adults. However, questions remain regarding the mechanistic role of CRF on cognitive and brain health. The purposes of this study were to investigate if higher pre-intervention CRF was associated with greater change in functional brain connectivity during an exercise intervention and to determine if the magnitude of change in connectivity was related to better post-intervention cognitive performance. The sample included low-active older adults (n = 139) who completed a 6-month exercise intervention and underwent neuropsychological testing, functional neuroimaging, and CRF testing before and after the intervention. A data-driven multi-voxel pattern analysis was performed on resting-state MRI scans to determine changes in whole-brain patterns of connectivity from pre- to post-intervention as a function of pre-intervention CRF. Results revealed a positive correlation between pre-intervention CRF and changes in functional connectivity in the precentral gyrus. Using the precentral gyrus as a seed, analyses indicated that CRF-related connectivity changes within the precentral gyrus were derived from increased correlation strength within clusters located in the Dorsal Attention Network (DAN) and increased anti-correlation strength within clusters located in the Default Mode Network (DMN). Exploratory analysis demonstrated that connectivity change between the precentral gyrus seed and DMN clusters were associated with improved post-intervention performance on perceptual speed tasks. These findings suggest that in a sample of low-active and mostly lower-fit older adults, even subtle individual differences in CRF may influence the relationship between functional connectivity and aspects of cognition following a 6-month exercise intervention.

A mechanistic understanding of cognitive performance deficits concurrent with vigorous intensity exercise.

This study aimed to evaluate whether cerebral oxygenation of the prefrontal cortex and associative-dissociative focus while completing the task mediate changes in cognition during exercise. Seventy-five young college-aged adults participated in this within-subjects randomized cross-over two-arm experimental design. During each session, participants completed a Stroop task four separate times: at baseline, two times during the exercise session, and at post-test. The experimental arm session involved participants cycling first at a moderate intensity, followed by cycling at a vigorous intensity. The active control arm session involved participants cycling at a very light intensity to ensure any effects were attributable to the level of exertion rather than the control of motor coordination. Cerebral oxygenation of the prefrontal cortex was assessed using fNIRS, while associate-dissociate attention was assessed using a self-report scale to provide insight into two hypothesized mechanisms which may contribute to alterations in cognition during exercise. Replicating well-established findings, results showed that during vigorous-intensity exercise, accuracy rates decreased for the most cognitively demanding conditions of the Stroop task, while reaction times were generally shorter compared to baseline. Neither shifting of attention in response to the dual-task nor prefrontal cortex oxygenation were observed to mediate cognitive deficits associated with vigorous exercise.

A friend in need is a friend indeed: Acute tandem rope skipping enhances inter-brain synchrony of socially avoidant individuals.

Team-based physical activity (PA) can improve social cognition; however, few studies have investigated the neurobiological mechanism underlying this benefit. Accordingly, a hyper-scanning protocol aimed to determine whether the interbrain synchrony (IBS) is influenced by an acute bout of team-based PA (i.e., tandem rope skipping). Specifically, we had socially avoidant participants (SOA, N=15 dyads) and their age-matched controls (CO, N=16 dyads) performed a computer-based cooperative task while EEG was recorded before and after two different experimental conditions (i.e., 30-min of team-based PA versus sitting). Phase locking value (PLV) was used to measure IBS. Results showed improved frontal gamma band IBS after the team-based PA compared to sitting when participants received successful feedback in the task (Mskipping = 0.016, Msittting = -0.009, p = 0.082, ηp2 = 0.387). The CO group showed a larger change in frontal and central gamma band IBS when provided failure feedback in the task (Mskipping = 0.017, Msittting = -0.009, p = 0.075, ηp2 = 0.313). Thus, results suggest that socially avoidant individuals may benefit from team-based PA via improved interbrain synchrony. Moreover, our findings deepen our understanding of the neurobiological mechanism by which team-based PA may improve social cognition among individuals with or without social avoidance.

Fitness, Gray Matter Volume, and Executive Function in Cognitively Normal Older Adults: Cross-Sectional Findings From the AGUEDA Trial.

The aim of the study is to investigate the association of cardiorespiratory fitness (CRF) and muscular strength indicators with gray matter volume (GMV) and to study whether fitness-related regions of GMV are associated to executive function (EF) in cognitively normal older adults. Ninety-one cognitively normal older adults (71.69 ± 3.91 years; 57.14% females) participated in this study from the AGUEDA trial. CRF was measured by a 2-km walking test and a 6-min walking test. Muscular strength was measured by handgrip, biceps curl, squats, and isokinetic strength tests. T1-weigthed images were obtained through a magnetic resonance scan. GMV was determined by voxel-based morphometric analysis. Standardized EF tests were performed. CRF did not show any positive association with GMV. Handgrip strength was positively associated with GMV (p < 0.001) in nine regions (ß from 0.6 to 0.8 and k from 106 to 1927) and knee extension strength in three regions (ß from 0.4 to 0.5 and k from 76 to 2776). Squats strength was negatively associated with GMV (p < 0.001) in two regions (ß = -0.3, k = 1102 and k = 152) and the 2-km walking test in one region (ß = -0.4, k = 99). Only handgrip strength-related GMV was associated with cognitive flexibility (p = 0.039, ß = 0.215) and spatial working memory (p < 0.03, ß 0.247-0.317), but not with EF score (p > 0.05). Muscular strength, but no CRF, may be positively related to GMV in cortical and subcortical regions, with implications for specific cognitive domains rather than the overall EF score. Specifically, handgrip strength was the indicator most associated with higher GMV, while squats strength and CRF were negatively related to GMV. ClinicalTrials.gov identifier: NCT05186090.

Changes in cardiovascular health and white matter integrity with aerobic exercise, cognitive and combined training in physically inactive healthy late-middle-aged adults: the "Projecte Moviment" randomized controlled trial.

INTRODUCTION: This is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits. METHODS: 109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements. RESULTS: A decrease in BMI (SMD = - 0.32, p = 0.039), waist circumference (SMD = - 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = - 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = - 0.34, p = 0.031) and DBP (SMD = - 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = - 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group. CONCLUSIONS: We found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT031123900.

Early morning physical activity is associated with healthier white matter microstructure and happier children: the ActiveBrains project.

The background of this study is to examine the associations of individual and combined early morning patterns (i.e., active commuting to school, physical activity before school, having breakfast and good sleep) with white matter microstructure (WMM) and, whether the associated white mater microstructure outcomes were related to mental health outcomes in children with overweight or obesity. 103 children with overweight or obesity (10.0 ± 1.1 years old, 42 girls) from the ActiveBrains project participated in this cross-sectional study. Early morning patterns and mental health indicators (i.e., self-esteem, optimism, positive and negative affect, stress, depression and anxiety) were self-reported by the children using validated questionnaires. WMM was assessed by magnetic resonance imaging using diffusion tensor imaging. When examined independently, early morning patterns were not related with WMM (all P > 0.05). However, the combination of early morning patterns was related with WMM (P < 0.05). Specifically, physically active early morning patterns (i.e., active commuting to school and physical activity before school) were associated with global fractional anisotropy (FA) (ß = 0.298, P = 0.013) and global radial diffusivity (RD) (ß = - 0.272, P = 0.021), as well as with tract-specific FA (ß = 0.314, P = 0.004) and RD (ß = - 0.234, P = 0.032) in the superior longitudinal fasciculus (SLF). Furthermore, combined physically active early morning pattern-associated global (i.e., FA and RD) and tract-specific (i.e., FA and RD in the SLF) WMM indicators were positively associated with happiness (ß absolute value range from 0.252 to 0.298, all P < 0.05). A combination of physically active early morning patterns may positively relate to white matter microstructure in children with overweight or obesity, and, in turn, happiness.

Emerging methods for measuring physical activity using accelerometry in children and adolescents with neuromotor disorders: a narrative review.

BACKGROUND: Children and adolescents with neuromotor disorders need regular physical activity to maintain optimal health and functional independence throughout their development. To this end, reliable measures of physical activity are integral to both assessing habitual physical activity and testing the efficacy of the many interventions designed to increase physical activity in these children. Wearable accelerometers have been used for children with neuromotor disorders for decades; however, studies most often use disorder-specific cut points to categorize physical activity intensity, which lack generalizability to a free-living environment. No reviews of accelerometer data processing methods have discussed the novel use of machine learning techniques for monitoring physical activity in children with neuromotor disorders. METHODS: In this narrative review, we discuss traditional measures of physical activity (including questionnaires and objective accelerometry measures), the limitations of standard analysis for accelerometry in this unique population, and the potential benefits of applying machine learning approaches. We also provide recommendations for using machine learning approaches to monitor physical activity. CONCLUSIONS: While wearable accelerometers provided a much-needed method to quantify physical activity, standard cut point analyses have limitations in children with neuromotor disorders. Machine learning models are a more robust method of analyzing accelerometer data in pediatric neuromotor disorders and using these methods over disorder-specific cut points is likely to improve accuracy of classifying both type and intensity of physical activity. Notably, there remains a critical need for further development of classifiers for children with more severe motor impairments, preschool aged children, and children in hospital settings.

Physical activity and brain amyloid beta: A longitudinal analysis of cognitively unimpaired older adults.

INTRODUCTION: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (Aß) over 15 years in a cohort of cognitively unimpaired older adults. METHODS: PA and Aß measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain Aß. Moderation analyses examined apolipoprotein E (APOE) ε4 carriage impact on the PA-Aß relationship. RESULTS: PA was not associated with brain Aß at baseline (ß = -0.001, p = 0.72) or over time (ß = -0.26, p = 0.24). APOE ε4 status did not moderate the PA-Aß relationship over time (ß = 0.12, p = 0.73). Brain Aß levels did not predict PA trajectory (ß = -54.26, p = 0.59). DISCUSSION: Our study did not identify a relationship between habitual PA and brain Aß levels. HIGHLIGHTS: Physical activity levels did not predict brain amyloid beta (Aß) levels over time in cognitively unimpaired older adults (≥60 years of age). Apolipoprotein E (APOE) ε4 carrier status did not moderate the physical activity-brain Aß relationship over time. Physical activity trajectories were not impacted by brain Aß levels.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

INTRODUCTION: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aß) measured by positron emission tomography were investigated. RESULTS: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aß at preclinical disease stages ß = -0.16 [-0.23 to -0.08], and a slower decline in multiple brain regions including hippocampal volume ß = 0.06 [0.03 to 0.08]. DISCUSSION: Exercise is associated with more favorable profiles of AD-related biomarkers in individuals with ADAD mutations. Exercise may have therapeutic potential for delaying the onset of AD; however, randomized controlled trials are vital to determine a causal relationship before a clinical recommendation of exercise is implemented. HIGHLIGHTS: Greater self-reported weekly exercise predicts slower declines in brain volume in autosomal dominant Alzheimer's disease (ADAD). Greater self-reported weekly exercise predicts slower accumulation of brain amyloid beta in ADAD. Associations varied depending on closeness to estimated symptom onset.

Early life factors and structural brain network in children with overweight/obesity: The ActiveBrains project.

BACKGROUND: The aims of this study were to investigate the association of early life factors, including birth weight, birth length, and breastfeeding practices, with structural brain networks; and to test whether structural brain networks associated with early life factors were also associated with academic performance in children with overweight/obesity (OW/OB). METHOD: 96 children with OW/OB aged 8-11 years (10.03 ± 1.16) from the ActiveBrains project were included. Early life factors were collected from birth records and reported by parents as weight, height, and months of breastfeeding. T1-weighted images were used to identify structural networks using a non-negative matrix factorization (NNMF) approach. Academic performance was evaluated by the Woodcock-Muñoz standardized test battery. RESULTS: Birth weight and birth length were associated with seven networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate nucleus, putamen, pallidum, nucleus accumbens, and amygdala. No associations were found for breastfeeding practices. None of the networks linked to birth weight and birth length were linked to academic performance. CONCLUSIONS: Birth weight and birth length, but not breastfeeding, were associated with brain structural networks in children with OW/OB. Thus, early life factors are related to brain networks, yet a link with academic performance was not observed. IMPACT: Birth weight and birth length, but not breastfeeding, were associated with several structural brain networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate, putamen, pallidum, accumbens and amygdala in children with overweight/obesity, playing a role for a normal brain development. Despite no academic consequences, other behavioral consequences should be investigated. Interventions aimed at improving optimal intrauterine growth and development may be of importance to achieve a healthy brain later in life.

Physical activity, sedentary time, and fitness in relation to brain shapes in children with overweight/obesity: Links to intelligence.

OBJECTIVES: To examine the association between physical activity, sedentary time, and physical fitness with the shapes of subcortical brain structures in children with overweight/obesity. Further, we analyzed whether differences in the shapes of subcortical brain structures were related to intelligence. We hypothesized that those children with higher physical activity levels, lower sedentary time, and better fitness, would show greater expansion of the brain regions analyzed, and these expansions would be associated with higher intelligence. STUDY DESIGN: 100 children (10.0 ± 1.1 years, 40 girls) were included in the analyses. Physical activity and sedentary time were measured by accelerometry, and physical fitness was evaluated by a fitness battery. Shapes of subcortical brain structures were assessed by magnetic resonance imaging. Intelligence was measured by the Kaufmann Brief Intelligence test. RESULTS: Physical activity was related to expansion of the right/left pallidum, right/left putamen, and right thalamus (p < 0.05). Higher sedentary time was related to contraction of the left thalamus and right nucleus accumbens (p < 0.05). Higher levels of cardiorespiratory fitness were associated with expansion of the right amygdala (p = 0.022). Greater strength in the upper-limb was related to expansion of the right/left pallidum and the left nucleus accumbens (p < 0.038), and contraction of the left amygdala (p = 0.030). Better speed-agility was associated with expansion of the left nucleus accumbens (p = 0.036). Physical activity- and fitness-related expansion of the right pallidum was associated with higher intelligence (all p < 0.05). CONCLUSION: Physical activity, sedentary time, and physical fitness were significantly related to the shapes of subcortical brain structures, which in turn were related to intelligence in children with overweight/obesity.

Neighborhood Walkability Is Associated with Physical Activity and Prediabetes in a Behavioral Weight Loss Study: a Secondary Analysis.

BACKGROUND: Socio-environmental factors may affect uptake and utility of behavioral interventions targeting weight loss and cardiometabolic health. To evaluate the relation of neighborhood walkability to physical activity (PA) and glucose control in a sample of adults with overweight/obesity participating in a weight loss study. METHODS: Secondary analysis of a 12-month behavioral weight loss intervention (2011-2015) using one-group pretest-posttest design. Neighborhood walkability was assessed via residential Walk Score (0-100) at study entry. Fasting plasma glucose (FPG) via phlebotomy and PA via waist-worn ActiGraph GT3X were assessed at baseline and end of study. Study variables included neighborhood walkability (car-dependent: Walk Score < 50 vs. walkable: Walk Score ≥ 50), prediabetes (FPG 100-125 mg/dL), and recommended PA (moderate to vigorous PA [MVPA] > 22 min/day). Generalized linear model with logit link results were reported as adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: The sample (N = 114) was mostly female (88.6%), white (83.3%), college educated (73.7%), and on average 51.4 ± 1.0 years of age. At baseline, persons residing in car-dependent neighborhoods tended to have higher income than those in walkable neighborhoods. Neighborhood walkability interacted with household income at study entry to predict participants' ability to meet the MVPA goal at 12 months (AOR = 13.52, 95% CI: 1.86-119.20). Those from walkable neighborhoods had 67% lower odds of having prediabetes compared to those from car-dependent neighborhoods (AOR = 0.33, 95% CI: 0.10-0.87) at 12 months. CONCLUSION: Our findings corroborate previous research characterizing the relationship between neighborhood walkability, PA, and prediabetes status. Key drivers of this impact warrant further investigation in a study with a larger, more diverse sample.

The relationship between objective physical activity and change in cognitive function.

INTRODUCTION: The current study investigated the association between objectively measured physical activity and cognition in older adults over approximately 8 years. METHODS: We utilized data from 199 cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, aged ≥60. Actigraphy was used to measure physical activity (intensity, total activity, and energy expenditure) at baseline. Cognition was assessed using a comprehensive cognitive battery every 18-months. RESULTS: Higher baseline energy expenditure predicted better episodic recall memory and global cognition over the follow-up period (p = 0.031; p = 0.047, respectively). Those with higher physical activity intensity and greater total activity also had better global cognition over time (both p = 0.005). Finally, higher total physical activity predicted improved episodic recall memory over time (p = 0.022). DISCUSSION: These results suggest that physical activity can preserve cognition and that activity intensity may play an important role in this association. HIGHLIGHTS: Greater total physical activity predicts preserved episodic memory and global cognition. Moderate intensity physical activity (>3.7 metabolic equivalents of task [MET]) predicts preserved global cognition. Expending > 373 kilocalories per day may benefit episodic memory and global cognition.

How little is enough? The feasibility of conducting a dose-escalation study for exercise training in people with stroke.

QUESTION: Is it feasible and safe to conduct an exercise dose-finding study in people with stroke? Is it possible to determine a minimal dose of exercise required to see clinically meaningful improvements in cardiorespiratory fitness? METHODS: Dose-escalation study. Twenty people with stroke (n=5 per cohort) who were able to walk independently participated in home-based, telehealth-supervised aerobic exercise sessions 3 d/week at moderate-vigorous intensity for 8 weeks. Dose parameters of frequency (3 d/week), intensity (55-85% of heart rate peak) and program length (8 weeks) were kept constant. The duration of exercise sessions was increased by 5 min per session from Dose 1 (10 min/session) to Dose 4 (25 min/session). Doses were escalated if safe and tolerable (< 33% of a cohort reaching a dose-limiting threshold). Doses were efficacious if ≥ 67% of a cohort increased peak oxygen consumption ≥ 2mL/kg/min. RESULTS: Target exercise doses were well adhered to, and the intervention was safe (480 exercise sessions delivered; one fall resulting in minor laceration) and tolerable (no participants met the dose-limiting threshold). None of the exercise doses met our criterion for efficacy. CONCLUSIONS: It is possible to conduct a dose-escalation trial for people with stroke. The small cohort sizes may have limited the ability to determine an efficacious minimum dose of exercise. Providing supervised exercise session at these prescribed doses via telehealth was safe. REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000460303).

Cognitive Aging and the Promise of Physical Activity.

Is the field of cognitive aging irretrievably concerned with decline and deficits, or is it shifting to emphasize the hope of preservation and enhancement of cognitive function in late life? A fragment of an answer comes from research attempting to understand the reasons for individual variability in the extent and rate of cognitive decline. This body of work has created a sense of optimism based on evidence that there are some health behaviors that amplify cognitive performance or mitigate the rate of age-related cognitive decline. In this context, we discuss the role of physical activity on neurocognitive function in late adulthood and summarize how it can be conceptualized as a constructive approach both for the maintenance of cognitive function and as a therapeutic for enhancing or optimizing cognitive function in late life. In this way, physical activity research can be used to shape perceptions of cognitive aging.

Association of physical activity levels and brain white matter in older Latino adults.

OBJECTIVE: Investigate the associations between self-reported physical activity (PA) engagement and white matter (WM) health (i.e. volume, integrity, and hyperintensities) in older Latinos. DESIGN: Cross-sectional study with community-dwelling older adults from predominantly Latino neighborhoods. Participants: Thirty-four cognitively healthy older Latinos from two different cohorts. Measurements: Participants self-reported demographic information, PA engagement [Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults] and magnetic resonance imaging (MRI). We used high-resolution three-dimensional T1- and T2-FLAIR weighted images and diffusion tensor imaging acquired via 3 T MRI. We performed a series of hierarchical linear regression models with the addition of relevant covariates to examine the associations between self-reported PA levels and WM volume, integrity, and hyperintensities (separately). We adjusted p-values with the use of the Benjamini-Hochberg's false discovery rate procedure. RESULTS: Higher reported levels of leisure-time moderate-to-vigorous PA were significantly associated with higher WM volume of the posterior cingulate (ß = 0.220, SE = 0.125, 95% CI 0.009-0.431, p = 0.047) and isthmus cingulate (ß = 0.212, SE = 0.110, 95% CI 0.001-0.443, p = 0.044) after controlling for intracranial volume. Higher levels of total PA were significantly associated with higher overall WM volume of these same regions (posterior cingulate: ß = 0.220, SE = 0.125, CI 0.024-0.421, p = 0.046; isthmus cingulate: ß = 0.220, SE = 0.125, 95% CI 0.003-0.393; p = 0.040). Significant p-values did not withstand Benjamini-Hochberg's adjustment. PA was not significantly associated with WM integrity or WM hyperintensities. CONCLUSION: Higher levels of PA, particularly higher leisure-time moderate-to-vigorous PA, might be associated with greater WM volume in select white matter regions key to brain network integration for physical and cognitive functioning in older Latinos. More research is needed to further confirm these associations.

Aerobic exercise, cardiorespiratory fitness, and the human hippocampus.

The hippocampus is particularly susceptible to neurodegeneration. Physical activity, specifically increasing cardiorespiratory fitness via aerobic exercise, shows promise as a potential method for mitigating hippocampal decline in humans. Numerous studies have now investigated associations between the structure and function of the hippocampus and engagement in physical activity. Still, there remains continued debate and confusion about the relationship between physical activity and the human hippocampus. In this review, we describe the current state of the physical activity and exercise literature as it pertains to the structure and function of the human hippocampus, focusing on four magnetic resonance imaging measures: volume, diffusion tensor imaging, resting-state functional connectivity, and perfusion. We conclude that, despite significant heterogeneity in study methods, populations of interest, and scope, there are consistent positive findings, suggesting a promising role for physical activity in promoting hippocampal structure and function throughout the lifespan.

Exercise interventions preserve hippocampal volume: A meta-analysis.

Hippocampal volume is a marker of brain health and is reduced with aging and neurological disease. Exercise may be effective at increasing and preserving hippocampal volume, potentially serving as a treatment for conditions associated with hippocampal atrophy (e.g., dementia). This meta-analysis aimed to identify whether exercise training has a positive effect on hippocampal volume and how population characteristics and exercise parameters moderate this effect. Studies met the following criteria: (a) controlled trials; (b) interventions of physical exercise; (c) included at least one time-point of hippocampal volume data before the intervention and one after; (d) assessed hippocampal volume using either manual or automated segmentation algorithms. Animal studies, voxel-based morphometry analyses, and multi-modal interventions (e.g., cognitive training or meditation) were excluded. The primary analysis in n = 23 interventions from 22 published studies revealed a significant positive effect of exercise on total hippocampal volume. The overall effect was significant in older samples (65 years of age or older) and in interventions that lasted over 24 weeks and had less than 150 min per week of exercise. These findings suggest that moderate amounts of exercise for interventions greater than 6 months have a positive effect on hippocampal volume including in older populations vulnerable to hippocampal atrophy.

Estrogen, brain structure, and cognition in postmenopausal women.

Declining estrogen levels before, during, and after menopause can affect memory and risk for Alzheimer's disease. Undesirable side effects of hormone variations emphasize a role for hormone therapy (HT) where possible benefits include a delay in the onset of dementia-yet findings are inconsistent. Effects of HT may be mediated by estrogen receptors found throughout the brain. Effects may also depend on lifestyle factors, timing of use, and genetic risk. We studied the impact of self-reported HT use on brain volume in 562 elderly women (71-94 years) with mixed cognitive status while adjusting for aforementioned factors. Covariate-adjusted voxelwise linear regression analyses using a model with 16 predictors showed HT use as positively associated with regional brain volumes, regardless of cognitive status. Examinations of other factors related to menopause, oophorectomy and hysterectomy status independently yielded positive effects on brain volume when added to our model. One interaction term, HTxBMI, out of several examined, revealed significant negative association with overall brain volume, suggesting a greater reduction in brain volume than BMI alone. Our main findings relating HT to regional brain volume were as hypothesized, but some exploratory analyses were not in line with existing hypotheses. Studies suggest lower levels of estrogen resulting from oophorectomy and hysterectomy affect brain volume negatively, and the addition of HT modifies the relation between BMI and brain volume positively. Effects of HT may depend on the age range assessed, motivating studies with a wider age range as well as a randomized design.