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Background: Meeting 24-h movement behaviors (24-HMB: physical activity [PA], screen time [ST], and sleep [SL]) recommendations may be associated with positive health outcomes among youth with specific mental, behavioral, and neurodevelopmental (MBD) conditions. However, temporal trends and disparities in meeting 24-HMB guidelines in these higher-risk groups have not been investigated, hampering the development of evidence-based clinical and public health interventions., Methods: Serial, cross-sectional analyses of nationally National Survey of Children's Health (NSCH) data (including U.S. youth aged 6-17 years with MBD conditions) were conducted. The time-trends survey data was conducted between 2016 and 2021. The prevalence of 24-HMB adherence estimates were reported for the overall sample and for various sociodemographic subgroups. The subgroups analyzed included: age group (children[aged 6 to 13 years], adolescents[aged 14 to 17 years]), sex, socioeconomic status, and ethnicity., Results: Data on 52,634 individuals (mean age, 12.0 years [SD,3.5]; 28,829 [58.0 %] boys) were analyzed. From 2016 to 2021 the estimated trend in meeting PA + ST + SL guidelines declined (-0.8 % [95%CI, -1.0 % to -0.5 %], P for trend <0.001), whereas meeting none of 24-HMB guidelines increased (2.2 % [1.8 % to 2.6 %], P for trend <0.001). White participants, children, and boys reported higher estimated prevalence of meeting full integrated (PA + ST + SL) guidelines., Discussion: The temporal trends observed in this study highlight the importance of consistently monitoring movement behavior among MBD youth and identifying variations by sociodemographic groups in meeting 24-HMB guidelines for health promotion within these vulnerable groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Exercise (EX) or cognitive and social enrichment (ENRICH) are 2 strategies for promoting cognition poststroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown., Methods: A 3-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (ie, ≥12 months since stroke). Participants were randomized to 2× per week EX, ENRICH, or balance and tone control (BAT). At baseline, device-measured sleep duration and efficiency were measured using wrist-worn actigraphy; self-reported quality was measured by Pittsburgh Sleep Quality Index (PSQI). Participants were categorized at baseline as having good or poor device-measured duration, device-measured efficiency, or self-reported quality based on PSQI. The primary cognitive outcome was Alzheimer's Disease Assessment Scale Plus (ADAS-Cog-Plus) measured at baseline, 6 months (end of intervention), and 12 months (6-month follow-up). We examined if baseline sleep categorizations (ie, good vs poor) moderated the effects of EX or ENRICH on ADAS-Cog-Plus., Results: We enrolled 120 participants in the trial (EX = 34; ENRICH = 34; BAT = 52). Sleep quality (ie, device-measured sleep efficiency or self-reported sleep quality) categorization moderated effects of EX (but not ENRICH) on ADAS-Cog-Plus. Compared with BAT participants with poor sleep quality, EX participants with poor sleep quality had better ADAS-Cog-Plus performance at 6 months (estimated mean difference for those with poor device-measured sleep efficiency: -0.48; 95% CI [-0.85, -0.10]; p = .010); estimated mean difference for those with poor self-reported sleep quality: -0.38; 95% CI [-0.70, -0.07]; p = .014). There was no effect of EX on ADAS-Cog-Plus for participants with good sleep quality. Device-measured sleep duration did not moderate intervention effects., Conclusions: Exercise is particularly beneficial in improving cognitive function in adults with chronic stroke and poor sleep quality., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: We investigated the prevalence and population attributable fraction (PAF) of 12 potentially modifiable risk factors for dementia in middle-aged and older Canadians., Methods: We conducted a cross-sectional study of 30,097 adults aged 45 to 85 with baseline data from the Canadian Longitudinal Study on Aging (2011‒2015). Risk factors and associated relative risks were taken from a highly cited systematic review. We calculated the prevalence of each risk factor using sampling weights. Individual PAFs were calculated both crudely and weighted for communality, and combined PAFs were calculated using both multiplicative and additive assumptions. Analyses were stratified by household income and repeated at CLSA's first follow-up (2015‒2018)., Results: The most prevalent risk factors were physical inactivity (63.8%; 95% CI, 62.8-64.9), hypertension (32.8%; 31.7-33.8), and obesity (30.8%; 29.7-31.8). The highest crude PAFs were physical inactivity (19.9%), traumatic brain injury (16.7%), and hypertension (16.6%). The highest weighted PAFs were physical inactivity (11.6%), depression (7.7%), and hypertension (6.0%). We estimated that the 12 risk factors combined accounted for 43.4% (37.3‒49.0) of dementia cases assuming weighted multiplicative interactions and 60.9% (55.7‒65.5) assuming additive interactions. There was a clear gradient of increasing prevalence and PAF with decreasing income for 9 of the 12 risk factors., Conclusion: The findings of this study can inform individual- and population-level dementia prevention strategies in Canada. Differences in the impact of individual risk factors between this study and other international and regional studies highlight the importance of tailoring national dementia strategies to the local distribution of risk factors., Competing Interests: Declarations. Conflict of interest: The authors declare they have no competing interests. Ethics: This study received ethics approval from the Hamilton Integrated Research Ethics Board (15408). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: NA., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)

Acknowledging the detrimental effects of prolonged sitting, this study examined the effects of an acute exercise break during prolonged sitting on executive function, cortical hemodynamics, and microvascular status. In this randomized crossover study, 71 college students completed three conditions: (i) uninterrupted sitting (SIT); (ii) SIT with a 15 min moderate-intensity cycling break (MIC); and (iii) SIT with a 15 min vigorous-intensity cycling break (VIC). Behavioral outcomes, retinal vessel diameters (central retinal artery equivalents [CRAE], retinal vein equivalents [CRVE], arteriovenous ratio [AVR]), cortical activation, and effective connectivity were evaluated. Linear mixed models identified significant positive effects of exercise conditions on behavioral reaction time (RT), error rate, and inverse efficiency score (β = -2.62, -0.19, -3.04: ps < 0.05). MIC and VIC conditions produced pre-to-post-intervention increases in CRAE and CRVE (β = 4.46, 6.34), frontal activation, and resting-state and task-state causal density (β = 0.37, 0.06) (ps < 0.05) compared to SIT; VIC was more beneficial for executive function and neurobiological parameters. The effect of AVR on average RT was mediated through task-based causal density (indirect effect: -0.82). Acutely interrupting prolonged sitting improves executive function, microvascular status, and cortical activation and connectivity, with causal density mediating the microvascular-executive function link., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: One-third of adults aged 65+ fall annually. Injuries from falls can be devastating for individuals and account for 1.5% of annual healthcare spending. With the growing ageing population, falls place increased strain on scarce health resources. Prevention strategies that target individuals at high risk for falls demonstrate the best value for money; however, limited efficiency (ie, cost-effectiveness) information for fall prevention interventions hinders the implementation of effective falls prevention programmes. Living systematic reviews provide a timely up-to-date evidence-based resource to inform clinical guidelines and health policy decisions. This protocol details the methodology for a living systematic review of the efficiency (ie, cost-effectiveness) of fall prevention interventions for older adults in three settings: community-dwelling, aged care and hospitals., Methods and Analysis: This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Peer-reviewed economic evaluations of controlled clinical trials or health state models will be included. Reports will be obtained through monthly systematic searches of CENTRAL (Ovid), CINAHL (EBSCO), Embase (Ovid), MEDLINE (Ovid), SCOPUS (Elsevier) and Web of Science (Clarivate) alongside snowballing and handsearching EconLit and the Tufts Cost Effectivness Analysis Registry. Screening, data extraction, quality assessment and risk of bias will be assessed by multiple reviewers. The primary outcomes will be the incremental cost-effectiveness (ie, incremental cost per fall prevented), incremental cost-utility (ie, incremental cost per quality-adjusted life year gained) or cost-benefit ratio. Additional outcomes will include falls and cost-related measures. All economic outcomes will be reported in a common year and currency. Results will be reported as a narrative synthesis; meta-analysis will be considered based on data quality, suitability and availability., Ethics and Dissemination: Ethical approval is not required as primary human data will not be collected. Results will be disseminated through peer-reviewed publications and a dedicated website., Prospero Registration Number: CRD42024532485., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Cognitive frailty is characterized by concurrent physical frailty and mild cognitive impairment and is associated with increased risk of falls. Exercise is an evidence-based strategy to prevent falls, but whether exercise reduces falls in people with cognitive frailty is unknown. We examined the effects of home-based exercise on subsequent falls among community-dwelling older adults with cognitive frailty who have previously fallen., Study Design: A sub-group analysis of a 12-month, single-blind, randomized controlled trial among 344 adults aged 70 years or more who had fallen within the past 12 months. Participants were randomized to either 12 months of home-based exercise (n=172) or usual care (n=172). In this sub-analysis, we included 192 participants with cognitive frailty (home-based exercise=93; usual care=99) with Short Physical Performance Battery scores ≤9/12 and Montreal Cognitive Assessment scores <26/30., Main Outcome Measures: Our primary analysis examined the effect of exercise on self-reported falls rate over 12 months. Secondary analyses investigated the intervention's effects on scores on the Short Physical Performance Battery and the Montreal Cognitive Assessment. We also explored whether greater than or equal to mean average monthly adherence (i.e., ≥45.5%) moderated treatment effects., Results: At 12 months, falls rates were 35% lower in the home-based exercise group compared with the usual care group (IRR=0.65; p=0.042). Score on the Short Physical Performance Battery significantly improved among home-based exercise participants with greater than or equal to mean adherence vs. those with less than mean adherence (estimated mean difference: 0.94; p=0.022)., Conclusions: Exercise is a promising strategy for reducing subsequent falls in people with cognitive frailty. Greater exercise adherence improved physical function in this population., Clinicaltrials: gov identifier: NCT01029171., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

There is growing evidence to suggest that lifestyle initiatives promote brain health and reduce dementia risk. However, there is comparatively limited research focused on lifestyle interventions among people living with dementia. Most recent systematic reviews of lifestyle interventions among people living with dementia centre on the impact of exercise on cognition; yet, functional abilities and quality of life are most consistently prioritized by people living with dementia, care partners, and healthcare professionals. There is insufficient evidence to inform guidelines on effective lifestyle interventions, programs, resources, and policies for people living with dementia. To address this knowledge gap, the objective of this study is to perform a systematic review to understand the impact of lifestyle interventions among people living with dementia. The specific research questions are: "What is the effectiveness of physical activity interventions on improving functional abilities and quality of life among community-dwelling people living with dementia?", "What is the effectiveness of healthy eating/nutrition on improving nutritional status or quality of life among community-dwelling people living with dementia?" and "Does the effectiveness of interventions vary depending on the components (single or multi), setting (in-home or community centre, geography), program structure, mode of delivery, dosage, and participant characteristics (sex/gender, ethno-cultural or language group, race, dementia type)?" The results from this review will inform recommendations of lifestyle interventions and their delivery among people living with dementia in the community. Trial registration: Systematic review registration PROSPERO #CRD42024509408., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Middleton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions-eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks-frontoparietal network (FPN) and default mode network (DMN)-significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes., (© 2024. The Author(s).)

Background: The relationship of cognition and the 24-h activity cycle (24-HAC), encompassing physical activity, sedentary behavior, and sleep, in older adults with mild cognitive impairment (MCI) remains uncertain. Distinct combinations of 24-HAC behaviors can characterize unique activity profiles and influence cognition. We aimed to characterize 24-HAC activity profiles in older adults with MCI and assess whether differences in cognition exist across profiles., Methods: We conducted a cross-sectional analysis utilizing baseline data from 3 randomized controlled trials involving 253 community-dwelling older adults (55 + years) with MCI (no functional impairment, dementia diagnosis, and Montreal Cognitive Assessment score <26/30). Using MotionWatch8© wrist-worn actigraphy (+5 days), we captured the 24-HAC. Cognition was indexed by the Alzheimer's Disease Assessment Scale Cognitive Plus (ADAS-Cog-Plus). Compositional data and latent profile analyses identified distinct 24-HAC activity profiles. Analysis of covariance examined whether 24-HAC activity profiles differed in cognition., Results: Four distinct activity profiles were identified. Profile 1 ("Average 24-HAC," n = 103) engaged in all 24-HAC behaviors around the sample average. Profile 2 ("Active Chillers," n = 70) depicted lower-than-average engagement in physical activity and higher-than-average sedentary behavior. Profile 3 ("Physical Activity Masters," n = 54) were the most active and the least sedentary. Profile 4 ("Sedentary Savants," n = 26) were the least active and the most sedentary. Sleep was similar across profiles. There were no significant differences in ADAS-Cog-Plus scores between 24-HAC activity profiles (p > .05)., Conclusions: Older adults with MCI exhibited four 24-HAC activity profiles conforming to recommended physical activity and sleep guidelines. Nonetheless, cognition was similar across these profiles., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Exercise training is an important strategy to counteract cognitive and brain health decline during aging. Evidence from systematic reviews and meta-analyses supports the notion of beneficial effects of exercise in cognitively unimpaired and impaired older individuals. However, the effects are often modest, and likely influenced by moderators such as exercise training parameters, sample characteristics, outcome assessments, and control conditions. Here, we discuss evidence on the impact of exercise on cognitive and brain health outcomes in healthy aging and in individuals with or at risk for cognitive impairment and neurodegeneration. We also review neuroplastic adaptations in response to exercise and their potential neurobiological mechanisms. We conclude by highlighting goals for future studies, including addressing unexplored neurobiological mechanisms and the inclusion of under-represented populations., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Slower walking is associated with changes in cortical volume and thickness. Computerized cognitive training (CCT) and exercise improve cortical volume and thickness and thus, may promote gait speed. Slowing of gait is predictive of Alzheimer's disease., Objective: To examine: 1) the effect of CCT, with or without physical exercise, on cortical volume and thickness and; 2) the association of changes in cortical volume and thickness with changes in gait speed., Methods: A subset of 124 adults ( n  = 53), aged 65-85 years, enrolled in an 8-week randomized controlled trial and completed T1-weighted MRI and 4-meter walk at baseline and 8 weeks. Participants were randomized to: 1) active control (BAT; n  = 19); 2) CCT ( n  = 17); or 3) CCT preceded by exercise (Ex-CCT; n  = 17). Change in cortical volume and thickness were assessed and compared across all groups using Freesurfer., Results: BAT versus CCT increased left rostral middle frontal gyrus volume ( p   = 0.027) and superior temporal gyrus thickness ( p  = 0.039). Ex-CCT versus CCT increased left cuneus thickness ( p  < 0.001) and right post central gyrus thickness ( p  = 0.005), and volume ( p  < 0.001). Ex-CCT versus BAT increased left ( p  = 0.001) and right ( p  = 0.020) superior parietal gyri thickness. There were no significant between-group differences in gait speed ( p  > 0.175). Increased left superior parietal volume ( p  = 0.036, r  = 0.340) and thickness ( p  = 0.002, r  = 0.348), right post central volume ( p  = .017, r  = 0.341) and thickness ( p  = 0.001, r  = 0.348), left banks of superior temporal sulcus thickness ( p  = 0.002, r  = 0.356), and left precuneus thickness ( p  < 0.001, r  = 0.346) were associated with increased gait speed., Conclusions: CCT with physical exercise, but not CCT alone, improves cortical volume and thickness in older adults. These changes may contribute to the maintenance of gait speed in aging., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Purpose: Cognitive deficits are common among stroke survivors and impact their functional independence. Despite the prevalence of cognitive deficits after stroke, cognitive function is largely overlooked in post-stroke care. The aim of this qualitative study was to explore the experiences of individuals living with post-stroke cognitive changes to understand the impact of these changes on their daily lives., Materials and Methods: Semi-structured interviews were conducted with a purposeful sample of thirteen community-dwelling adults 50 years and older with chronic stroke who self-identified cognitive changes post-stroke. Interviews were transcribed and an inductive thematic analysis was completed., Results: Four key themes were identified: 1) inability to maintain everyday activities; 2) experiencing emotional responses to living with post-stroke cognitive changes; 3) a shrinking social world and; 4) seeking care for cognitive health post-stroke., Conclusions: Post-stroke cognitive changes were described by participants as a driving force behind negative shifts in their daily lives, emotional health, and social connections after stroke. Despite seeking care for their post-stroke cognitive changes, many participants were unable to find support in mainstream healthcare. There is a demonstrated need to further elucidate the gaps in care for post-stroke cognitive deficits and implement community interventions targeting cognitive health post-stroke.

Objective: Increased intraindividual variability (IIV) of cognitive performance is a marker of cognitive decline in older adults. Whether computerized cognitive training (CCT) and aerobic exercise counteracts cognitive decline by reducing IIV is unknown. We investigated the effects of CCT with or without aerobic exercise on IIV in older adults., Methods: This was a secondary analysis of an 8-week randomized controlled trial. Older adults (aged 65-85 years) were randomized to CCT alone ( n = 41), CCT with aerobic exercise ( n = 41), or an active control group ( n = 42). The CCT group trained using the Fit Brains® platform 3×/week for 1 hr (plus 3×/week of home-based training). The CCT with aerobic exercise group received 15 min of walking plus 45 min of Fit Brains® 3×/week (plus 3×/week of home-based training). The control group received sham exercise and cognitive training (3×/week for 1 hr). We computed reaction time IIV from the Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test (Flanker), and Pattern Comparison Processing Speed Test (PACPS)., Results: Compared with the control group, IIV reduced in a processing speed task (PACPS) following CCT alone (mean difference [95% confidence interval]: -0.144 [-0.255 to -0.034], p < 0.01) and CCT with aerobic exercise (-0.113 [-0.225 to -0.001], p < 0.05). Attention (Flanker congruent) IIV was reduced only after CCT with aerobic exercise (-0.130 [-0.242 to -0.017], p < 0.05)., Conclusions: A CCT program promoted cognitive health via reductions in IIV of cognitive performance and combining it with aerobic exercise may result in broader benefits.

Vascular contributions to cognitive impairment and dementia, specifically cerebral small vessel disease (CSVD), are the second most common cause of dementia. Currently, there are no specific pharmacological treatments for CSVD, and the use of conventional antidementia drugs is not recommended. Exercise has the potential to prevent and mitigate CSVD-related brain damage and improve cognitive function. Mechanistic pathways underlying the neurocognitive benefits of exercise include the control of vascular risk factors, improving endothelial function, and upregulating exerkines. Notably, the therapeutic efficacy of exercise may vary by exercise type (ie, aerobic versus resistance training) and biological sex; thus, studies designed specifically to examine these moderating factors within a CSVD context are needed. Furthermore, future research should prioritize resistance training interventions, given their tremendous therapeutic potential. Addressing these knowledge gaps will help us refine exercise recommendations to maximize their therapeutic impact in the prevention and mitigation of CSVD., Competing Interests: Disclosures Dr Liu-Ambrose served on the executive team of Synaptitude Brain Health, Inc (she does not receive personal fees for these roles). The other authors report no conflicts.

We conducted a meta-analysis of randomized controlled trials investigating the effects of aerobic exercise training (AET) lasting ≥ 4 weeks on hippocampal volume and cardiorespiratory fitness (CRF) in cognitively unimpaired, healthy older individuals. Random-effects robust variance estimation models were used to test differences between AET and controls, while meta-regressions tested associations between CRF and hippocampal volume changes. We included eight studies (N = 554) delivering fully supervised AET for 3 to 12 months (M = 7.8, SD = 4.5) with an average AET volume of 129.85 min/week (SD = 45.5) at moderate-to-vigorous intensity. There were no significant effects of AET on hippocampal volume (SMD = 0.10, 95% CI - 0.01 to 0.21, p = 0.073), but AET moderately improved CRF (SMD = 0.30, 95% CI 0.12 to 0.48, p = 0.005). Improvement in CRF was not associated with changes in hippocampal volume (b SE  = 0.05, SE = 0.51, p = 0.923). From the limited number of studies, AET does not seem to impact hippocampal volume in cognitively unimpaired, healthy older individuals. Notable methodological limitations across investigations might mask the lack of effects., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

A sedentary lifestyle offers immediate gratification, but at the expense of long-term health. It is thus critical to understand how the brain evaluates immediate rewards and long-term health effects in the context of deciding whether to engage in moderate-to-vigorous physical activity (MVPA) or sedentary behaviour (SB). In this secondary analysis of a 6-month randomized controlled trial to increase MVPA and reduce SB among community-dwelling adults, we explored how neural activity during an executive control task was associated with MVPA and SB levels. At baseline, a subset of participants (n = 26/61) underwent task-based functional magnetic resonance imaging (fMRI) to examine neural activity underlying executive control using the Now/Later task. MVPA and SB were measured objectively using the Sensewear Mini at baseline, and 2, 4, and 6 months follow-up. We then examined the associations of baseline neural activation underlying executive control with: (1) baseline MVPA or SB; and (2) changes in MVPA and SB over 6 months. Our results determined that there is a complex neurocognitive system associated with MVPA levels, while SB appears to lack any neurocognitive control. In other words, MVPA appears to require neurocognitive effort, while SB may be the default behavioural pattern in adults., (© 2023. The Author(s).)

Introduction: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs., Methods: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia., Results: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD., Conclusion: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management., (© 2024 S. Karger AG, Basel.)

Objectives: To assess a remote physiotherapist (PT) counselling intervention using self-monitoring tools for improving self-management ability, physical activity participation, and health outcomes in people with rheumatoid arthritis (RA)., Methods: Eligible participants were randomly assigned to receive group education, a Fitbit®, a self-monitoring app, and PT counselling phone calls (Immediate Group). The Delayed Group received a monthly e-newsletter until week 26, and then the intervention. The primary outcome was Patient Activation Measure (PAM-13). Participants were assessed at baseline, 27 weeks (the primary end point) and 53 weeks. Secondary outcomes included disease activity, pain, fatigue, depression, sitting/walking habits, daily physical activity time, and daily awake sedentary time. Generalized Linear Mixed-effect Models (GLMMs) were used to assess the effect of the intervention on the change of each outcome measure from the initiation to 27 weeks after the intervention., Results: Analysis included 131 participants (91.6% women; 80.2% completed during the COVID-19 pandemic). The mean change of PAM-13 at 27 weeks was 4.6 (SD = 14.7) in the Immediate Group vs -1.6 (SD = 12.5) in the Delayed Group. The mean change in Delayed Group at 53 weeks (after the 26-week intervention) was 3.6 (SD = 14.6). Overall, the intervention improved PAM-13 at 27 weeks post-intervention from the GLMM analysis (adjusted coefficient: 5.3; 95% CI: 2.0, 8.7; p = <0.001). Favourable intervention effects were also found in disease activity, fatigue, depression, and self-reported walking habit., Conclusion: Remote counselling paired with self-monitoring tools improved self-management ability in people with RA. Findings of secondary outcomes indicate that the intervention had a positive effect on symptom management., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Limited mobility in older adults consistently predicts both morbidity and mortality. As individuals age, the rates of mobility disability increase from 1.0% in people aged 15-24 to 20.6% in adults over 65 years of age. Physical activity can effectively improve mobility in older adults, yet many older adults do not engage in sufficient physical activity. Evidence shows that increasing physical activity by 50 min of moderate intensity physical activity in sedentary older adults with mobility limitations can improve mobility and reduce the incidence of mobility disability. To maximize the healthy life span of older adults, it is necessary to find effective and efficient interventions that can be delivered widely to prevent mobility limitations, increase physical activity participation, and improve quality of life in older adults. We propose a randomized controlled trial to assess the effect of a physical activity health coaching intervention on mobility in older adults with mobility limitations., Methods: This randomized controlled trial among 290 (145 per group) community-dwelling older adults with mobility limitations, aged 70-89 years old, will compare the effect of a physical activity health coaching intervention versus a general healthy aging education program on mobility, as assessed with the Short Physical Performance Battery. The physical activity health coaching intervention will be delivered by exercise individuals who are trained in Brief Action Planning. The coaches will use evidence-based behavior change techniques including goal-setting, action planning, self-monitoring, and feedback to improve participation in physical activity by a known dose of 50 min per week. There will be a total of 9 health coaching or education sessions delivered over 26 weeks with a subsequent 26-week follow-up period, wherein both groups will receive the same duration and frequency of study visits and activities., Discussion: The consequences of limited mobility pose a significant burden on the quality of life of older adults. Our trial is novel in that it investigates implementing a dose of physical activity that is known to improve mobility in older adults utilizing a health coaching intervention., Trial Registration: ClinicalTrials.gov Protocol Registration System: NCT05978336; registered on 28 July 2023., (© 2023. The Author(s).)

Importance: Cognitive impairment is prevalent in survivors of stroke, affecting approximately 30% of individuals. Physical exercise and cognitive and social enrichment activities can enhance cognitive function in patients with chronic stroke, but their cost-effectiveness compared with a balance and tone program is uncertain., Objective: To conduct a cost-effectiveness and cost-utility analysis of multicomponent exercise or cognitive and social enrichment activities compared with a balance and tone program., Design, Setting, and Participants: This economic evaluation used a Canadian health care systems perspective and the Vitality study, a randomized clinical trial aimed at improving cognition after stroke with a 6-month intervention and a subsequent 6-month follow-up (ie, 12 months). The economic evaluation covered the duration of the Vitality trial, between June 6, 2014, and February 26, 2019. Participants were community-dwelling adults aged 55 years and older who experienced a stroke at least 12 months prior to study enrollment in the Vancouver metropolitan area, British Columbia, Canada. Data were analyzed from June 1, 2022, to March 31, 2023., Interventions: Participants were randomly assigned to twice-weekly classes for 1 of the 3 groups: multicomponent exercise program, cognitive and social enrichment activities program, or a balance and tone program (control)., Main Outcomes and Measures: The primary measures for the economic evaluation included cost-effectiveness (incremental costs per mean change in cognitive function, evaluated using the Alzheimer Disease Assessment Scale-Cognitive-Plus), cost-utility (incremental cost per quality-adjusted life-year gained), intervention costs, and health care costs. Since cognitive benefits 6 months after intervention cessation were not observed in the primary randomized clinical trial, an economic evaluation at 12 months was not performed., Results: Among 120 participants (mean [SD] age, 71 [9] years; 74 [62%] male), 34 were randomized to the multicomponent exercise program, 34 were randomized to the social and cognitive enrichment activities program, and 52 were randomized to the balance and tone control program. At the end of the 6-month intervention, the cost per mean change in Alzheimer Disease Assessment Scale-Cognitive-Plus score demonstrated that exercise was more effective and costlier compared with the control group in terms of cognitive improvement with an incremental cost-effectiveness ratio of CAD -$8823. The cost per quality-adjusted life-year gained for both interventions was negligible, with exercise less costly (mean [SD] incremental cost, CAD -$32 [$258]) and cognitive and social enrichment more costly than the control group (mean [SD] incremental cost, CAD $1018 [$378]). The balance and tone program had the lowest delivery cost (CAD $777), and the exercise group had the lowest health care resource utilization (mean [SD] $1261 [$1188]) per person., Conclusions and Relevance: The findings of this economic evaluation suggest that exercise demonstrated potential for cost-effectiveness to improve cognitive function in older adults with chronic stroke during a 6-month intervention.

Introduction: In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data., Methods and Analysis: Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated., Ethics and Dissemination: Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups., Competing Interests: Competing interests: ES has been paid consulting fees by Eli Lilly and Alnylam. No other authors have conflicts of interest to report., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Prolonged bed rest is prevalent among middle-aged and older adults and is associated with multiple negative health outcomes. Therefore, it is important that we better understand the utility of exercise training as a countermeasure to the adverse effects of bed rest. We examined the effect of exercise training on intraindividual variability in cognitive performance among adults aged 55-65 exposed to 14 days of physical inactivity modelled via 6° head-down tilt bed rest., Methods: The study is a non-blinded, parallel-group, proof-of-concept randomized controlled trial. Twenty-three healthy middle-aged and older adults (12 males, 11 females) aged 55-65 were randomized to: (1) 14 days of 6° head-down tilt bed rest (Control) or (2) 14 days of 6° head-down tilt bed rest with daily exercise (Exercise). The National Institutes of Health Toolbox Cognitive Battery assessed executive functions (Flanker incongruent/congruent and Dimensional Change Card Sort) and processing speed (Pattern Comparison). We assessed cognitive function at baseline, 6° head-down tilt bed rest midpoint, completion, and seven days following completion. We indexed intraindividual variability with two metrics: (1) residual intraindividual standard deviation and (2) intraindividual coefficient of variation. Flanker congruent and incongruent residual intraindividual standard deviations were the primary outcomes. Linear mixed models assessed between-group differences and the moderating effect of biological sex., Results: At bed rest completion, Exercise had significantly lower (better) Flanker incongruent residual intraindividual standard deviation (estimated mean difference = -3.63, 95%CI -6.10;-1.17, p = 0.005) and intraindividual coefficient of variation (estimated mean difference = -0.10, 95%CI -0.19;-0.003, p = 0.022) vs. Control. Sex moderated the effect of exercise on Flanker incongruent intraindividual coefficient of variation. Exercise females had significantly lower intraindividual coefficient of variation vs. Control (estimated mean difference = -0.23; 95%CI -0.34;-0.12, p < 0.001). There were no significant between-group differences in processing speed intraindividual variability and summary scores of executive functions and processing speed (ps > 0.05)., Conclusion: Exercise training during bed rest preserved intraindividual variability of executive functions but not processing speed., Trial Registration: ClinicalTrials.gov NCT04964999., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Methods: Twenty individuals in the chronic stage of stroke walked: (1) at their normal pace, (2) slower than normal, and (3) as fast as possible. Functional near-infrared spectroscopy was used to assess bilateral prefrontal, premotor, sensorimotor, and posterior parietal cortices during walking., Results: No significant differences in laterality were observed between walking speeds. The ipsilesional prefrontal cortex was overall more active than the contralesional prefrontal cortex. Premotor and posterior parietal cortex activity were larger during slow and fast walking compared to normal-paced walking with no differences between slow and fast walking. Greater increases in brain activation in the ipsilesional prefrontal cortex during fast compared to normal-paced walking related to greater gait speed modulation., Conclusions: Brain activation is not linearly related to gait speed. Ipsilesional prefrontal cortex, bilateral premotor, and bilateral posterior parietal cortices are important areas for gait speed modulation and could be an area of interest for neurostimulation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Shannon B. Lim et al.)

Importance: Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI)., Objective: To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone., Design, Setting, and Participants: This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022., Interventions: Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly., Main Outcomes and Measures: Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months., Results: Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant., Conclusions and Relevance: In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI., Trial Registration: ClinicalTrials.gov Identifier: NCT02808676.

Background: As the aging population grows, there is an increasing need to develop accessible interventions against risk factors for cognitive impairment and dementia, such as cerebral small vessel disease (CSVD). The progression of white matter hyperintensities (WMHs), a key hallmark of CSVD, can be slowed by resistance training (RT). We hypothesize RT preserves white matter integrity and that this preservation is associated with improved cognitive and physical function., Objective: To determine if RT preserves regional white matter integrity and if any changes are associated with cognitive and physical outcomes., Methods: Using magnetic resonance imaging data from a 12-month randomized controlled trial, we compared the effects of a twice-weekly 60-minute RT intervention versus active control on T1-weighted over T2-weighted ratio (T1w/T2w; a non-invasive proxy measure of white matter integrity) in a subset of study participants (N = 21 females, mean age = 69.7 years). We also examined the association between changes in T1w/T2w with two key outcomes of the parent study: (1) selective attention and conflict resolution, and (2) peak muscle power., Results: Compared with an active control group, RT increased T1w/T2w in the external capsule ( p  = 0.024) and posterior thalamic radiations ( p  = 0.013) to a greater degree. Increased T1w/T2w in the external capsule was associated with an increase in peak muscle power ( p  = 0.043) in the RT group., Conclusion: By maintaining white matter integrity, RT may be a promising intervention to counteract the pathological changes that accompany CSVD, while improving functional outcomes such as muscle power., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Trail Making Test B were completed at baseline, post-intervention, and 6- and 12-months poststroke, administered using standardized guidelines. Using the DOSE data, we used mixed-effect spline regression to model participants' trajectories of cognitive recovery, controlling for relevant covariates. Participants (Usual Care n  = 25, DOSE n  = 50) were 56.7(11.7) years old, and 27(10) days post stroke. For the MoCA, there were statistically significant Group × Trajectory( p  = 0.019), and Group × ΔTrajectory ( p  = 0.018) interactions with a substantial clinically meaningful difference, from +5.44 points/month improvement of the DOSE group compared to +1.59 points/month improvement with Usual Care during the 4-week intervention. The DSST and Trails B improved over time but were not different between groups. Taking advantage of this early difference may lend support to continued efforts to increase intensity, during and after discharge from inpatient rehabilitation, to improve cognition. Clinical trial registration : www.clinicaltrials.gov, NCT01915368., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peters, Lohse, Klassen, Liu-Ambrose, Dukelow, Bayley, Hill, Pooyania, Yao and Eng.)

Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin D 3 (10,000 IU/pill) or a placebo capsule was ingested three times per week for 20-weeks. Using the CONN toolbox, we measured FBC change (Post-Pre) across four statistical models that collapsed for and/or included some or all study arms. We conducted Pearson correlations between FBC change and changes in physical and cognitive functioning. Our sample included 120 participants (mean age: 73.89 ± 6.50). Compared to the pure control, physical exercise (model one; p-False Discovery Rate (FDR) < 0.01 & < 0.05) with cognitive training (model two; p-FDR =  < 0.001), and all three interventions combined (model four; p-FDR =  < 0.01) demonstrated an increase in FBC between regions of the Default-Mode Network (i.e., hippocampus and angular gyrus). After controlling for false discovery rate, there were no significant correlations between change in connectivity and change in cognitive or physical function. Physical exercise alone appears to be as efficacious as combined interventional strategies in altering FBC, but implications for behavioral outcomes remain unclear., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

Background: Aerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex., Methods: We used data from a single-blind randomized controlled trial in older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Fifty-eight older adults were randomly assigned to either the 6 months, three times per week progressive aerobic training (AT) group or the usual care plus education control (CON) group. The secondary aim of the parent study included executive functions which were assessed with the Trail Making Test (B-A) and the Digit Symbol Substitution Test at baseline and trial completion at 6 months., Results: Analysis of covariance, controlling for baseline global cognition and baseline executive functions performance (Trail Making Test or Digit Symbol Substitution Test), tested the three-way interaction between experimental group (AT, CON), BDNFval66met genotype (Val/Val carrier, Met carrier), and biological sex (female, male). Significant three-way interactions were found for the Trail Making Test (F(1,48) = 4.412, p < 0.04) and Digit Symbol Substitution Test (F(1,47) = 10.833, p < 0.002). Posthoc analyses showed female Val/Val carriers benefited the most from 6 months of AT compared with CON for Trail Making Test and Digit Symbol Substitution Test performance. Compared with CON, AT did not improve Trail Making Test performance in male Val/Val carriers or Digit Symbol Substitution Test performance in female Met carriers., Conclusions: These results suggest that future randomized controlled trials should take into consideration BDNF genotype and biological sex to better understand the beneficial effects of AT on cognitive function in vascular cognitive impairment to maximize the beneficial effects of exercise and help establish exercise as medicine for cognitive health., (© 2023. The Author(s).)

Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson's correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Background: Myelin loss is a feature of cerebral small vessel disease (cSVD). Although physical activity levels may exert protective effects over cSVD pathology, its specific relationship with myelin content in people living with the cSVD is unknown. Thus, we investigated whether physical activity levels are associated with myelin in community-dwelling older adults with cSVD and mild cognitive impairment., Methods: Cross-sectional data from 102 individuals with cSVD and mild cognitive impairment were analyzed (mean age [SD] = 74.7 years [5.5], 63.7% female). Myelin was measured using a magnetic resonance gradient and spin echo sequence. Physical activity was estimated using the Physical Activity Scale for the Elderly. Hierarchical regression models adjusting for total intracranial volume, age, sex, body mass index, and education were conducted to determine the associations between myelin content and physical activity. Significant models were further adjusted for white matter hyperintensity volume., Results: In adjusted models, greater physical activity was linked to higher myelin content in the whole-brain white matter (R2change = .04, p = .048). Greater physical activity was also associated with myelin content in the sagittal stratum (R2change = .08, p = .004), anterior corona radiata (R2change = .04, p = .049), and genu of the corpus callosum (R2change = .05, p = .018). Adjusting for white matter hyperintensity volume did not change any of these associations., Conclusions: Physical activity may be a strategy to maintain myelin in older adults with cSVD and mild cognitive impairment. Future randomized controlled trials of exercise are needed to determine whether exercise increases myelin content., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health., Methods: To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates., Results: Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group., Conclusion: The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus wild-type (Val/Val)) influenced the ability of voluntary running to enhance cognition and hippocampal neurogenesis in mice. Middle-aged C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved performance in both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A growing body of research is exploring the potential added health benefits of exercise when performed outdoors in nature versus indoors. This systematic review aimed to compare the effects of exercise in outdoor environments versus indoor environments on psychological health, physical health, and physical activity behaviour. We searched nine databases from inception to March 2021 for English language, peer-reviewed articles: MEDLINE, Embase, PubMed, Scopus, Web of Science, CINAHL, SportsDiscus, GreenFile, and CENTRAL. We included randomized and non-randomized trials that compared multiple bouts of exercise in outdoor versus indoor environments, and that assessed at least one outcome related to physical health, psychological health, or physical activity behaviour. Due to minimal outcome overlap and a paucity of studies, we performed a narrative synthesis. We identified 10 eligible trials, including 7 randomized controlled trials, and a total of 343 participants. Participant demographics, exercise protocols, and outcomes varied widely. In the 10 eligible studies, a total of 99 comparisons were made between outdoor and indoor exercise; all 25 statistically significant comparisons favoured outdoor exercise. Interpretation of findings was hindered by an overall high risk of bias, unclear reporting, and high outcome heterogeneity. There is limited evidence for added health or behaviour benefits of outdoor exercise versus indoor exercise. Rigorous randomized controlled trials are needed with larger samples and clear reporting.

Introduction: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency., Methods: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements., Results: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR., Conclusion: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: To provide a comprehensive CERT (Consensus on Exercise Reporting Template)-based description of the resistance exercise program implemented in the AGUEDA (Active Gains in brain Using Exercise During Aging) study, a randomized controlled trial investigating the effects of a 24-week supervised resistance exercise program on executive function and related brain structure and function in cognitively normal older adults., Design and Participants: 90 cognitively normal older adults aged 65 to 80 were randomized (1:1) to a: 1) resistance exercise group; or a 2) wait-list control group. Participants in the exercise group (n = 46) performed 180 min/week of resistance exercise (3 supervised sessions per week, 60 min/session) for 24 weeks., Intervention: The exercise program consisted of a combination of upper and lower limb exercises using elastic bands and the participant's own body weight as the main resistance. The load and intensity were based on the resistance of the elastic bands (7 resistances), number of repetitions (individualized), motor complexity of exercises (3 levels), sets and rest (3 sets/60 sec rest), execution time (40-60 sec) and velocity (as fast as possible)., Settings: The maximum prescribed-target intensity was 70-80% of the participants' maximum rate of perceived exertion (7-8 RPE). Heart rate, sleep quality and feeling scale were recorded during all exercise sessions. Those in the wait-list control group (n = 44) were asked to maintain their usual lifestyle. The feasibility of AGUEDA project was evaluated by retention, adherence, adverse events and cost estimation on the exercise program., Results and Conclusions: This study details the exercise program of the AGUEDA trial, including well-described multi-language manuals and videos, which can be used by public health professionals, or general public who wish to implement a feasible and low-cost resistance exercise program. The AGUEDA exercise program seems to be feasible by the high retention (95.6%) and attendance rate (85.7%), very low serious adverse event (1%) and low economic cost (144.23 € /participant/24 weeks). We predict that a 24-week resistance exercise program will have positive effects on brain health in cognitively normal older adults., Competing Interests: The author declare no conflict of interest to disclose.

Introduction: Epidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. This is possibly due to insufficient exercise intensities. The aim of the Balance, Resistance, And INterval (BRAIN) Training Trial is to determine the effects of two forms of exercise, high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) each compared with a sham exercise control group on cognition in older adults with MCI., Methods and Analysis: One hundred and sixty community-dwelling older (≥ 60 years) people with MCI have been randomised into the trial. Interventions are delivered supervised 2-3 days per week for 12 months. The primary outcome measured at baseline, 6 and 12 months is performance on a cognitive composite score measuring the executive domain calculated from a combination of computerised (NeuroTrax) and paper-and-pencil tests. Analyses will be performed via repeated measures linear mixed models and generalised linear mixed models of baseline, 6-month and 12-month time points, adjusted for baseline values and covariates selected a priori. Mixed models will be constructed to determine the interaction of GROUP × TIME., Ethics and Dissemination: Ethical approval was obtained from the University of Sydney (HREC Ref.2017/368), University of Queensland (HREC Ref. 2017/HE000853), University of British Columbia (H16-03309), and Vancouver Coastal Health Research Institute (V16-03309) Human Research Ethics. Dissemination will be via publications, conference presentations, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers.It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT and POWER on subclinical markers of disease., Trial Registration Number: ACTRN12617001440314 Australian New Zealand Clinical Trials Registry., Competing Interests: Competing interests: JMH, JSC and TL-A report funding received from a subcontract between USYD and their institutions to support the conduct of this study; PSS receives funding from a NHMRC Investigator Grant and is a member of Advisory Committee for Biogen Australia and Roche Australia., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sleep and physical activity (PA) are important for the maintenance of executive functions. Whether these lifestyle factors independently contribute to associated neural correlates of executive functions is unknown. We therefore investigated the independent associations of PA and sleep with neural activity during executive performance using task-based functional magnetic resonance imaging (fMRI). Baseline data from a subset of participants (n = 29) enrolled in a randomised trial were used for this cross-sectional analysis. We measured PA, sleep duration and efficiency for 7 days using the SenseWear Mini and examined neural activity underlying response inhibition using the Go/NoGo executive performance task. Brain activation patterns during the NoGo condition were contrasted to activation patterns during the Go condition (i.e., NoGo-Go). We constructed two separate models (controlling for age, sex, and education) to examine the independent associations of (i) PA and sleep duration; and (ii) PA and sleep efficiency with brain activation. Significant clusters were corrected for multiple comparisons (p < 0.05) to determine region-specific activation patterns. The mean (SD) participant age was 61 (9) years, and 79% were female. PA was independently associated with greater task-related blood-oxygen-level dependent (BOLD) signal activity in the left cingulate gyrus; longer sleep duration was independently associated with greater BOLD signal activity in the left putamen. Higher sleep efficiency was independently associated with increased BOLD signal activity in the left hippocampus. PA, sleep duration, and efficiency are each independently associated with greater neural activity underlying response inhibition, which further illustrates that PA and sleep are each uniquely important for brain health., (© 2022 European Sleep Research Society.)

Objectives: Physical activity (PA) and total sleep time (TST) are each associated with cognition; however, whether these relationships vary by age and biological sex is unclear. We examined the relationships of PA or TST with cognition, and whether age and sex moderated these relationships, using baseline data from the Canadian Longitudinal Study on Aging (CLSA; 2010-2015)., Study Design: A cross-sectional analysis of participants from the Comprehensive cohort of the CLSA with complete PA and sleep data (n = 20,307; age range 45-86 years)., Main Outcome Measures: PA and TST were measured using the Physical Activity Scale for the Elderly (PASE) and self-reported TST over the past month. Cognition was indexed using a three-factor structural equation model (i.e., memory, executive function, and verbal fluency)., Results: Non-linear restricted cubic spline models indicated that PA and TST explained statistically significant (p < 0.01) but modest variance of each cognitive domain (<1 % of 23-24 % variance). Age and sex did not moderate associations of PA with any cognitive domain. However, age and sex moderated relationships of TST with cognition, whereby: 1) associations of TST with memory decreased with age for males and females; and 2) males and females had different age-associated relationships of TST with executive function and verbal fluency., Conclusions: PA and TST modestly contribute to multiple domains of cognition across middle and older adulthood. Importantly, the association of PA with cognition does not appear to vary across middle or older adulthood, nor does it vary by biological sex; however, TST appears to have a complex relationship with multiple domains of cognition which is both age- and sex-dependent., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Poor sleep and chronic fatigue are common in people with chronic stroke (i.e. ≥ 6 months post-stroke). Exercise training is a viable, low-cost therapy for promoting sleep and reducing fatigue; however, the effects of exercise on sleep and fatigue in people with chronic stroke are unclear. Thus, we conducted a systematic review ascertaining the effects of exercise on sleep and fatigue in people with chronic stroke. We systematically searched EMBASE, MEDLINE, AgeLine, the Cochrane Database of Systematic Reviews, CINAHL, SPORTDiscus, SCOPUS, and reference lists of relevant reviews for articles that examined the effects of exercise on sleep or fatigue in chronic stroke. Search results were limited to adults ≥ 18 years, randomized controlled trials, non-randomized trials, and pre-post studies, which were published in English and examined the effects of exercise on sleep or fatigue in people with chronic stroke. We extracted study characteristics and information on the measurement of sleep and fatigue, and assessed study quality and risk of bias using the CONSORT criteria and Cochrane risk-of-bias tool, respectively. We found two studies that examined the effects of exercise on sleep, and two that examined the effects of exercise on fatigue. All studies reported positive effects of exercise training on sleep and fatigue; however, there were concerns of bias and study quality in all studies. There is preliminary evidence that exercise promotes sleep and reduces fatigue in people with chronic stroke; however, the extent to which exercise impacts these health parameters is unclear., (© 2022 European Sleep Research Society.)

We investigated whether myelin is associated with gait parameters in older adults with cerebral small vessel disease (cSVD). Cross-sectional data from sixty-four participants with cSVD and mild cognitive impairment were analyzed. Myelin was assessed via MRI multi-echo gradient and spin echo T 2 relaxation sequence, indexed as myelin water fraction (MWF). Gait was assessed using an electronic walkway. Hierarchical regression models adjusting for total intracranial volume, age, sex, Mini-Mental State Examination, and body mass index were conducted to determine associations between MWF and gait parameters. Significant models were further adjusted for white matter hyperintensities. Sixty-four participants were included (mean [SD], age = 75.2y [5.4], 62.5% female). In adjusted models, lower MWF in the cingulum (p = 0.015), superior longitudinal fasciculus (p = 0.034), posterior corona radiata (p = 0.039), and body of the corpus callosum (p = 0.040) was associated with higher cycle time variability. White matter hyperintensities weakened these associations. Lower myelin in specific white matter tracts may contribute to higher gait variability, increasing the overall risk of mobility impairment., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Among older adults, health-related quality of life (HRQoL) and falls are associated. Generic patient-reported outcomes measures (PROMs) assess individual's HRQoL. The role for PROMs, a potential tool for predicting subsequent falls, remains under-explored. Our primary aim was to determine whether a baseline PROMs assessment of HRQoL may be a useful tool for predicting future falls., Methods: A secondary analysis of a 12-month randomized clinical trial (RCT) of a home-based exercise program among 344 adults (67% female), aged ≥ 70 years, with ≥ 1 falls in the prior year who were randomized (1:1) to either a home-based exercise program (n = 172) or usual care (n = 172). A negative binomial regression model with total falls count as the dependent variable evaluated the main effect of the independent variable-baseline HRQoL (measured by the Short-Form-6D)-controlling for total exposure time and experiment group (i.e., exercise or usual care) for the total sample. For the usual care group alone, the model controlled for total exposure time., Results: For the total sample, the rate of subsequent total falls was significantly predicted by baseline HRQoL (IRR = 0.044; 95% CI [0.005-0.037]; p = .004). For the usual care group, findings were confirmed with wider confidence intervals and the rate of prospective total falls was significantly predicted by baseline HRQoL (IRR = 0.025; 95% CI [0.001-0.909]; p = .044)., Conclusion: These findings suggest the ShortForm-6D should be considered as part of falls prevention screening strategies within a Falls Prevention Clinic setting. Trial Registrations ClinicalTrials.gov Protocol Registration System. Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 . Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596 ., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)