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BackgroundOlder 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.MethodsTo 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.ResultsSignificant 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.ConclusionThe 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.

BackgroundPhysical 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.MethodsTo 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.ResultsMaintaining 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.ConclusionsThese 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.

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.

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]

Gonadal and stress hormones modulate neuroplasticity and behaviour. This review focuses on our findings over the past decade on the effects of estrogens and androgens on hippocampal neurogenesis, hippocampus-dependent learning and memory and the effects of reproductive experience in the rodent. Evidence suggests that acute estradiol initially enhances and subsequently suppresses cell proliferation in the dentate gyrus of adult female rodents. Repeated exposure to estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents while, testosterone and dihydrotestosterone upregulate hippocampal neurogenesis in adult male rodents. Estradiol dose-dependently affects different brain regions involved in working memory (prefrontal cortex, hippocampus), reference memory (hippocampus) and conditioned place preference (amygdala). Pregnancy and motherhood differentially regulate adult hippocampal neurogenesis and spatial working memory in the dam after weaning. These studies and others demonstrate that the female brain responds to steroid hormones differently than the male brain. It is of the upmost importance to investigate the effects on neuroplasticity and behaviour in both the male and the female, particularly when modelling diseases that exhibit sex differences in incidence, etiology or treatment. Keywords: estradiol, neurogenesis, learning and memory, hippocampus, reproductive experience Les hormones de stress et gonadiques modulent la neuroplasticite et le comportement. Cette revue met l'accent sur Ies decouvertes des dernieres decennies quant aux effets des estroge, nes et des androgbnes sur la neurogenese de l'hippocampe, l'apprentissage dependant de l'hippocampe et les effets de l'experience de reproduction chez les rongeurs. Les donnees suggbrent qu'une quantite importante d'oestradiol augmente initialement puis diminue subsequemment la proliferation cellulaire dans le gyrus dente des rongeurs femelles adultes. Une exposition repetee a l'oestradiol module la neurogenese de l'hippocampe et la mort cellulaire chez les rongeurs femelles, mais pas chez les males, alors que la testosterone et la dihydrotestosterone regulent positivement la neurogenese de l'hippocampe chez les rongeurs adultes males. L'oestradiol peut affecter, independamment de la dose, differentes regions du cerveau impliquees dans la memoire de travail (cortex prefrontal et hippocampe), la memoire de reference (hippocampe) et la preference spatiale conditionnee (amygdale). La grossesse et la maternite regulent differemment la neurogenese de l'hippocampe et la memoire de travail chez les rongeurs femelles adultes apres la periode de sevrage. Ces etudes et d'autres demontrent que le cerveau de la femelle reagit differemment aux hormones steroidiennes que le cerveau des males. Il est de la plus grande importance d'en etudier Ies effets sur la neuroplasticite et le comportement autant chez les males que les femelles, particulierement lors de la modelisation de pathologies dont l'incidence, l'etiologie ou le traitement differe selon le sexe. Mots-cles: oestradiol, neurogenese, apprentissage et memoire, hippocampe, experience de reproduction