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Exercise training is among the main strategies that have been proposed to promote cognitive and brain health outcomes in older individuals with and without cognitive impairment. The effects of exercise on cognition are mediated, in part, by structural and functional adaptations in the brain, including changes in gray matter volumes and white matter microstructural integrity. Muscular contractions during exercise produce a category of cytokines referred to as myokines, which represent a potential molecular pathway mediating neuroplastic adaptations and associated cognitive improvements in response to exercise. Understanding the ideal combination of exercise training parameters across populations and life stages could lead to interventions that promote greater effects on cognitive and brain health outcomes. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Sex differences for subsequent falls and falls risk factors in community-dwelling older adults who have fallen are unknown. Our aim was to: (1) compare the number of falls between sexes, (2) identify modifiable falls risk factors, and (3) explore the interaction of sex on falls risk factors in older adults who fall. Methods: Four hundred sixty-two community dwellers seeking medical attention after an index fall were recruited from the Vancouver Falls Prevention Clinic and participated in this 12-month prospective cohort study. Ninety-six participants were part of a randomized controlled trial of exercise. Falls were tracked with monthly falls calendars. Demographics, falls risk measures, and the number of subsequent falls were compared between sexes. A principal component analysis (PCA) was employed to reduce the falls risk measures to a smaller set of factors. The PCA factors were used in negative binomial regression models to predict the number of subsequent falls. Age, exposure time (i.e., number of falls monitoring days), and prescribed exercise (yes/no) were used as covariates, and sex (male/female) and PCA factors were used as main effects. The interaction of sex by PCA factor was then included. Results: Males fell more over 12 months (males: 2.80 ± 6.86 falls; females: 1.25 ± 2.63 falls) than females, and poorer executive function predicted falls in males. Four PCA factors were defined – impaired cognition and mobility, low mood and self-efficacy, mobility resilience, and perceived poor health – each predicted the number of falls. The sex by mobility resilience interaction suggested that mobility resilience was less protective of falls in males. Conclusion: Modifiable risk factors related to cognition, physical function, psychological wellbeing, and health status predicted subsequent falls. In males, better mobility was not as protective of falls compared with females. This may be due to males' poorer executive function, contributing to decreased judgement or slowed decision-making during mobility. These results may inform efficacious sex-specific falls prevention strategies. [ABSTRACT FROM AUTHOR]

Aerobic training (AT) can promote cognitive function in adults with Subcortical Ischemic Vascular Cognitive Impairment (SIVCI) by modifying cardiovascular risk factors. However, pre-existing cardiovascular health may attenuate the benefits of AT on cognitive outcomes in SIVCI. We examined whether baseline cardiovascular risk moderates the effect of a 6-month progressive AT program on executive functions with a secondary analysis of a randomized controlled trial in 71 adults, who were randomized to either: (1) 3×/week progressive AT; or (2) education program (CON). Three executive processes were measured: (1) response inhibition by Stroop Test; (2) working memory by digits backward test; and (3) set shifting by the Trail Making Test. Baseline cardiovascular risk was calculated using the Framingham cardiovascular disease (CVD) Risk Score (FCRS), and participants were classified as either low risk (< 20% FCRS score; LCVR) or high risk (≥ 20% FCRS score; HCVR). A complete case analysis (n = 58) was conducted using an analysis of covariance (ANCOVA) to evaluate between-group differences in the three executive processes. A significant interaction was found between cardiovascular risk group and intervention group (AT or CON) for the digit span backward and the Trail Making Test. AT improved performance compared with CON in those with LCVR, while in those with HCVR, AT did not improve performance compared with CON. Baseline cardiovascular risk significantly moderates the efficacy of AT on cognition. Our findings highlight the importance of intervening early in the disease course of SIVCI, when cardiovascular risk may be lower, to reap maximum benefits of aerobic exercise. [ABSTRACT FROM AUTHOR]

Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood.Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD.Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05.Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β  = -0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132).Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function. [ABSTRACT FROM AUTHOR]

The number of older people worldwide living with cognitive impairment and neurodegenerative diseases is growing at an unprecedented rate. Despite accumulating evidence that engaging in physical activity is a promising primary behavioral strategy to delay or avert the deleterious effects of aging on brain health, a large degree of variation exists in study findings. Thus, before physical activity and exercise can be prescribed as "medicine" for promoting brain health, it is imperative to understand how different biological factors can attenuate or amplify the effects of physical activity on cognition at the individual level. In this review article, we briefly discuss the current state of the literature, examining the relationship between physical activity and brain health in older adults and we present the argument that biological sex is a potent moderator of this relationship. Additionally, we highlight some of the potential neurobiological mechanisms underlying this sex difference for this relatively new and rapidly expanding line of research. [ABSTRACT FROM AUTHOR]

Abstract Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be an important source of heterogeneity seen in cognitive aging, although the specific relationship between this polymorphism and cognition remains controversial and may depend on the sex of participants. We assessed 2668 older black and white adults and fit linear mixed models to digit symbol substitution test (DSST) performance assessed in years 0 (baseline), 4, 7, and 9 to examine the interaction between sex and BDNF genotype on the intercept (i.e., estimated baseline DSST) and change in DSST over 9 years, adjusted for covariates. Sex interacted with BDNF genotype to predict DSST intercept (F [1,1599] = 7.4, p < 0.01) and 9-year change (F [1,1183] = 4.1, p = 0.04) in white participants only. Initially, white male Val/Val carriers had lower DSST scores (37.6, SE = 0.8) in comparison with male Met carriers (difference, −1.7; 95% CI, −3.2 to −0.3) and female Val/Val carriers (difference, −5.6; 95% CI, −6.8 to −4.3). White female Met carriers showed a slower rate of change (annual rate of change = −0.6, SE = 0.1) in comparison with female Val/Val carriers (difference, −0.2; 95% CI, −0.4 to −0.02) and male Met carriers (difference, −0.3; 95% CI, −0.5 to −0.02). Our findings suggest that BDNF Val66Met and sex should be considered in future endeavors aimed at treating or preventing neurodegenerative disorders. Highlights • BDNF Val66Met polymorphism effect on cognitive decline is controversial and may be due to an interaction with biological sex. • There was an interaction such that the Met allele was protective against declines in executive functioning for females, but in white participants only. • Interaction between sex and BDNF Val66Met polymorphism was not seen in black participants. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the population is aging and the number of individuals diagnosed with dementia is rising rapidly. Currently, there are no effective pharmaceutical cures. Hence, identifying lifestyle approaches that may prevent, delay, or treat cognitive impairment and dementia in older adults is becoming increasingly important. Computerized Cognitive Training (CCT) is a promising strategy to combat cognitive decline. Yet, the underlying mechanisms of the effect of CCT on cognition remain poorly understood. Hence, the primary objective of this systematic review was to examine peer-reviewed literature ascertaining the effect of CCT on both structural and functional neuroimaging measures among older adults to gain insight into the underlying mechanisms by which CCT may benefit cognitive function.Methods: In accordance with PRISMA guidelines, we used the following databases: MEDLINE, EMBASE, and CINAHL. Two independent reviewers abstracted data using pre-defined terms. These included: main study characteristics such as the type of training (i.e., single- versus multi-domain), participant demographics (age ≥ 50 years; no psychiatric conditions), and the inclusion of neuroimaging outcomes. The Physiotherapy Evidence Database (PEDro) scale was used to assess quality of all studies included in this systematic review.Results: Nine studies were included in this systematic review, with four studies including multiple MRI sequences. Results of this systematic review are mixed: CCT was found to increase and decrease both brain structure and function in older adults. In addition, depending on region of interest, both increases and decreases in structure and function were associated with behavioural performance.Conclusions: Of all studies included in this systematic review, results from the highest quality studies, which were two randomized controlled trials, demonstrated that multi-domain CCT could lead to increases in hippocampal functional connectivity. Further high quality studies that include an active control, a sample size calculation, and an appropriate training dosage, are needed to confirm these findings and their relation to cognition. [ABSTRACT FROM AUTHOR]

• Exercise helps maintain executive functions during prolonged bed rest in adults aged 55–65 years. • Exercise mitigates the effects of bed rest on the intraindividual variability in cognition. • The benefits of exercise for executive functions are more robust in women. 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. 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. 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 (p s > 0.05). Exercise training during bed rest preserved intraindividual variability of executive functions but not processing speed. ClinicalTrials.gov NCT04964999 [ABSTRACT FROM AUTHOR]