No abstract

Age is accompanied by differences in the organization of functional brain networks, which impact behavior in adulthood. Functional networks tend to become less segregated and more integrated with age. However, sex differences in network segregation declines with age are not well-understood. Further, network segregation in the context of female reproductive stage is relatively understudied, though unmasking such relationships would be informative for elucidating biological mechanisms that contribute to sex-specific differences in aging. In the current work, we used data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository to evaluate differences in resting-state network segregation as a product of sex and reproductive stage. Reproductive stage was categorized using the Stages of Reproductive Aging Workshop (STRAW+10) criteria. Replicating prior work, we investigated the following functional networks: auditory, cerebellar-basal ganglia, cingulo-opercular task control, default mode, dorsal attention, fronto-parietal task control, salience, sensory somatomotor mouth, sensory somatomotor hand, ventral attention, and visual. First, our results mirror findings from previous work indicating that network segregation is lower with increasing age. Second, when analyzing associations between network segregation and age within each sex separately, we find differences between females and males. Finally, we report significant effects of reproductive stage on network segregation, though these findings are likely driven by age. Broadly, our results suggest that impacts of sex are important to evaluate when investigating network segregation differences across adulthood, though further work is needed to determine the unique role of menopause and sex hormones on the organization of functional brain networks within aging females.

Metabolic Syndrome (MetS) is associated with increased rates of mortality and increased risk for developing dementia. Changes in brain structure and cognitive functioning have been reported within the literature. However, research examining cognitive performance in individuals with MetS is limited, inconclusive, and focuses primarily on older cohorts. As such, the effect of MetS on cognitive functioning earlier in the lifespan is unclear. This study aimed to investigate cognitive performance in young, middle-aged, and older adults with multiple metabolic and vascular risk factors in a sample of community dwelling participants (N = 128). Participants were administered a comprehensive neuropsychological battery and self-report measures. As expected, older adults performed more poorly than young and middle-aged adults across most assessments. Relative to controls, individuals with MetS reported greater hunger and disinhibited eating. MetS participants performed more poorly on Color-Word Interference: Inhibition. Additionally, when weight was accounted for, there was a significant relationship between MetS and select executive functioning tasks in middle-aged adults. These findings suggest that aspects of executive functioning may be impaired in MetS and could be further impacted by excess weight in middle-age. Future studies aimed at investigating potential causal relationships between metabolic and vascular risk factors, disinhibited eating, and executive dysfunction may provide insight into effective intervention targets to prevent MetS.

Sex hormones fluctuate over the course of the female lifespan and are associated with brain health and cognition. Thus, hormonal changes throughout female adulthood, and with menopause in particular, may contribute to sex differences in brain function and behavior. Further, sex hormones have been correlated with sleep patterns, which also exhibit sex-specific impacts on the brain and behavior. As such, the interplay between hormones and sleep may contribute to late-life brain and behavioral outcomes in females. Here, in a sample of healthy middle-aged and older females (n = 79, ages 35-86), we evaluated the effect of hormone-sleep interactions on cognitive and motor performance as well as cerebellar-frontal network connectivity. Salivary samples were used to measure 17β-estradiol, progesterone, and testosterone levels while overnight actigraphy was used to quantify sleep patterns. Cognitive behavior was quantified using the composite average of standardized scores on memory, processing speed, and attentional tasks, and motor behavior was indexed with sequence learning, balance, and dexterity tasks. We analyzed resting-state connectivity correlations for two specific cerebellar-frontal networks: a Crus I to dorsolateral prefrontal cortex network and a Lobule V to primary motor cortex network. In sum, results indicate that sex hormones and sleep patterns interact to predict cerebellar-frontal connectivity and behavior in aging females. Together, the current findings further highlight the potential consequences of endocrine aging in females and suggest that the link between sex hormones and sleep patterns may contribute, in part, to divergent outcomes between sexes in advanced age.

Age is accompanied by differences in the organization of functional brain networks, which impact behavior in adulthood. Functional networks become less segregated and more integrated with age. However, sex differences in network segregation declines with age are not well‐understood. Further, network segregation in the context of female reproductive stage is relatively understudied, though unmasking such relationships would be informative for elucidating biological mechanisms that contribute to sex‐specific differences in aging. In the current work, we used data from the Cambridge Centre for Ageing and Neuroscience (Cam‐CAN) repository to evaluate differences in resting‐state network segregation as a product of sex and reproductive stage. Reproductive stage was categorized using the Stages of Reproductive Aging Workshop (STRAW+10) criteria. Replicating prior work, we investigated the following functional networks: auditory, cerebellar‐basal ganglia, cingulo‐opercular task control, default mode, dorsal attention, fronto‐parietal task control, salience, sensory somatomotor mouth, sensory somatomotor hand, ventral attention, and visual. First, our results mirror findings from previous work indicating that network segregation is lower with increasing age. Second, when analyzing associations between network segregation and age within each sex separately, we find qualitative differences between females and males. Finally, we report significant effects of reproductive stage on network segregation, though these findings are likely driven by age. Broadly, our results suggest that impacts of sex may be important to evaluate when investigating network segregation differences across adulthood, though further work is needed to determine the unique role of menopause and sex hormones on the organization of functional brain networks within aging females.