Search

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: 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.)

It is unclear whether cardiometabolic risk shares an interactive relationship with age-associated differences in cognition, and whether this relationship varies by biological sex. We conducted a cross-sectional analysis using baseline data from the Canadian Longitudinal Study on Aging (CLSA; 2010-2015) to examine whether 1) cardiometabolic risk has an interactive relationship with age-associated cognition; and 2) interactive effects are sex-dependent. We measured memory, executive function, and verbal fluency in the Comprehensive cohort ( N  = 25 830; 45-86 years). Each cognitive domain was modeled using restricted cubic splines for age and each cardiometabolic risk factor (HbA1c, HSCRP, TG, and LDL and HDL cholesterol). Sex was included as a predictor in all models. Wald χ 2 statistics were used to determine the relative importance of age, cardiometabolic risk, sex, and their interactive effects on cognition. Age was the most important variable in each model (proportion χ 2  = 34%-48%). Biological sex was the second most important variable for memory (proportion χ 2  = 26%) but was unimportant for executive function and verbal fluency (proportion χ 2  = 3%-5%). Cardiometabolic risk factors were unimportant predictors in each model (proportion χ 2  = 1%-3%). Two- and 3-way interactions between cardiometabolic risk, age, and sex were also unimportant (proportion χ 2  = 0%-2%). Thus, cardiometabolic risk factors did not meaningfully account for age-associated differences in cognition, and these associations (or lack thereof) did not vary by sex. Novelty: Males have poorer age-associated cognitive performance than females. Females and males differ in cardiometabolic risk across middle and older adulthood. Cardiometabolic risk has a small association with age-associated cognition, and there are no sex differences in this relationship.

Objective: To examine potential sex differences in the relationship between arterial stiffness and global cognitive function and executive functions., Methods: Baseline data from 80 older adults were included from two randomized controlled trials (NCT02669394 and NCT02737878). Arterial stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV). Cognitive function assessment included global cognition (Mini-Mental State Examination [MMSE]) and executive functions (set shifting [Trail Making Test Part B minus A], inhibition [Stroop Test], and working memory [Verbal Digit Span Backwards Test]). Separate statistical models were constructed to assess the effect of cf-PWV on each cognitive outcome for females and males. Each statistical model controlled for Framingham cardiovascular disease risk score and education., Results: Higher cf-PWV was associated with impaired MMSE performance in males (β = -0.48; p = 0.018), but not females (p ≥ 0.389). For executive processes, higher cf-PWV was associated with impaired Trail Making Test Part B minus A (β = 0.56; p = 0.005) and Stroop Test (β = 0.59; p = 0.004) in males, but not in females (ps ≥ 0.108). cf-PWV was not significantly associated with Verbal Digit Span Forward minus Backward Test in males or females (ps ≥ 0.108)., Conclusions: Arterial stiffness is more strongly associated with cognitive impairment in males than females. These results further elucidate the interplay between vascular health and cognitive function by providing support for sex-specific mechanisms., Competing Interests: Declarations of Competing Interest All authors report no conflicts on interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Dementia is one of the most pressing health care issues of this century. As no curative treatment for dementia exists, research efforts are growing to identify effective lifestyle interventions to prevent or delay onset. One such promising strategy that promotes cognitive and brain health is engaging in physical exercise. However, current exercise recommendations are imprecise. To advance the potential of exercise as a preventative and treatment strategy, important questions regarding moderators (ie, biological sex and age) are being addressed in the literature. Biological sex is recognized as an important variable to consider in exercise efficacy on brain health, with females showing greater cognitive gains. This may be related to sex differences in underlying mechanisms. Here, we argue to better understand the sex differences in exercise efficacy, the timing of exercise intervention should also be considered. Specifically, we present the hypothesis that midlife in females is a critical window for the implementation of exercise as an early intervention to promote brain health and prevent dementia. Further, we speculate that exercise interventions targeting midlife will be of critical importance for the female brain, as females exit this period of the lifespan at greater risk for cognitive impairment. Given the potential sex differences in dementia risk and prevalence, it is imperative to assess potential sex differences in exercise efficacy as an early intervention during midlife., (© 2020 Federation of American Societies for Experimental Biology.)

Background: Physical activity (PA) is a promising strategy for the promotion of brain health, although substantial variation exists in the effects of PA at the individual level. Given the greater prevalence and faster progression of Alzheimer's disease in women compared to men, and known sex differences in brain architecture, analysis of sex differences in the relationship between PA, cognition, and brain region volumes is warranted., Methods: To address this, we conducted secondary analyses of data from the Health, Aging, and Body Composition study. To determine whether longitudinal changes in PA over 10 years predicted declines in global cognitive functioning and executive functions and processing speed differently in males and females, latent growth curve modeling was utilized. Magnetic resonance imaging was performed at year 10, and the hippocampus and dorsolateral prefrontal cortex were identified as regions of interest., Results: Maintaining PA over 10 years predicted less declines in executive functions and processing speed in females but not males. Maintaining PA over 10 years was significantly associated with greater volume of the left dorsolateral prefrontal cortex, a brain region involved in executive functions, in year 10 in females only. Maintaining physical activity was associated with better global cognitive function in both males and females, and also predicted volume of the left hippocampus, albeit in different directions with females showing a negative relationship and males showing a positive relationship., Conclusions: These findings suggest that the relationship of PA with cognition and its neurobiological correlates differ by sex, with females apparently benefiting from PA to a greater extent than males. Development of personalized, tailored exercise recommendations to promote healthy brain aging should account for sex differences., (© The Author(s) 2019. 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.)

Exercise is a non-pharmacological strategy to mitigate the deleterious effects of aging on brain health. However, a large amount of variation exists in its efficacy. Sex of participants and exercise type are two possible factors contributing to this variation. To better understand this, we conducted a concurrent systematic review and meta-analysis of cognitively healthy older adults. Executive functions, episodic memory, visuospatial function, word fluency, processing speed and global cognitive function were examined for exercise- and sex-dependent effects. For executive functions, three types of exercise interventions - aerobic training, resistance training, and multimodal training (i.e., both aerobic and resistance training) - were associated with larger effect sizes in studies comprised of a higher percentage of women compared to studies with a lower percentage of women. This suggests that women's executive processes may benefit more from exercise than men. Regardless of sex, compared to control, all three exercise training approaches enhanced visuospatial function, but only multimodal training enhanced episodic memory. Overall, aerobic training led to greater benefits than resistance training in global cognitive function and executive functions, while multimodal combined training led to greater benefits than aerobic training for global cognitive function, episodic memory, and word fluency. Possible underlying mechanisms, including brain-derived neurotrophic factor and sex steroid hormones, are discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aerobic training (AT) is a promising, non-pharmacological intervention to mitigate the deleterious effects of aging and disease on brain health. However, a large amount of variation exists in its efficacy. This is a secondary analysis of a randomized controlled trial of AT in 71 older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1) whether sex moderates the relationship between AT and executive functions, and 2) the role of brain derived neurotrophic factor (BDNF) and gains in functional fitness capacity. Older adults were randomly assigned to either 6-month, thrice-weekly AT or to usual care plus education (CON). At baseline, trial completion, and 6-month follow-up, executive functions were assessed with the Trail Making Test (A & B), verbal digits forward and backward test, and the Stroop Test. Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared with CON, AT significantly improved Trail Making Test performance in females but not males, an effect that was retained at follow-up. AT significantly increased BDNF levels in females but decreased levels in males. On the other hand, AT led to significant gains in functional fitness capacity in males only. This study provides evidence that sex differences exist in AT efficacy on brain health as well as in the biological mechanisms subserving AT.

Pregnancy and motherhood constitute periods of tremendous hormonal variation that orchestrate parturition, lactation, maternal care, maternal aggression, and recognition of offspring, among other functions. Cognitive processing also varies during pregnancy and motherhood and may serve an adaptive function in preparation for parturition and rearing. Additionally, maternal experience may have enduring consequences for the brain, behavior, and cognition long after offspring are mature. However, the early postpartum period also renders women psychologically vulnerable as approximately 15% of women experience postpartum depression, with estimates of 50-80% reporting a milder form of depression termed "maternal blues." This review will present literature on pregnancy- and parity-related changes in both cognition and affect and how these changes likely involve plastic changes within the hippocampus, a region that is sensitive to reproductive hormones. Further, this review will discuss steroid and peptide hormones that may contribute to affective and cognitive disruptions during pregnancy and postpartum. Research in this area may reveal insight into how pregnancy and motherhood alter the likelihood of developing postpartum depression and related disorders.

Background: Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain., Scope of Review: This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats., Major Conclusions: Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning., General Significance: Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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]

Physical activity is a promising strategy for dementia prevention and disease modification. Here, we provide a narrative review of the current evidence from epidemiological and intervention studies on the role of physical activity and exercise in promoting cognitive health in older adults both without and with cognitive impairment. We highlight some of the potential underlying mechanisms and discuss biological sex as a potential moderating factor. We conclude with limitations and future directions for this rapidly expanding line of research. [ABSTRACT FROM AUTHOR]

The societal value of strategies that delay the onset and progression of dementia cannot be overstated. Physical activity-unstructured and structured-is a promising, cost-effective strategy for the promotion of brain health. However, a large degree of variation exists in its efficacy. Therefore, to increase its utility as 'medication' for healthy cognitive ageing, it is imperative to identify key moderators and mediators of the positive effects of targeted exercise training on brain health. In this commentary, we focus on the type of targeted exercise training, the determinants of individual variation, including biological sex and genotypic factors, and the mechanisms by which exercise exerts its influence on the brain. We argue that a better understanding of these factors will allow for evidence-based, personalised, tailored exercise recommendations that go beyond the one-size-fits-all approach to successfully combat dementia. [ABSTRACT FROM AUTHOR]