We investigated sex differences in the association between a measure of physical health, cardiorespiratory fitness (CRF), and brain function using resting-state functional connectivity fMRI. We examined these sex differences in the default, frontoparietal control, and cingulo-opercular networks, assemblies of functionally connected brain regions known to be impacted by both age and fitness level. Healthy older adults ( n = 49; 29 women) were scanned to obtain measures of intrinsic connectivity within and across these 3 networks. We calculated global efficiency (a measure of network integration) and local efficiency (a measure of network specialization) using graph theoretical methods. Across all three networks combined, local efficiency was positively associated with CRF, and this was more robust in male versus female older adults. Furthermore, global efficiency was negatively associated with CRF, but only in males. Our findings suggest that in older adults, associations between brain network integrity and physical health are sex-dependent. These results underscore the importance of considering sex differences when examining associations between fitness and brain function in older adulthood. NEW & NOTEWORTHY We examined the association between cardiorespiratory fitness and resting state functional connectivity in several brain networks known to be impacted by age and fitness level. We found significant associations between fitness and measures of network integration and network specialization, but in a sex-dependent manner, highlighting the interplay between sex differences, fitness, and aging brain health. Our findings underscore the importance of considering sex differences when examining associations between fitness and brain function in older adulthood.

Menopause is associated with cognitive decline, and hormone therapies (HTs) may improve cognition depending on type and timing of HTs. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin 6 months later, and all rats were trained in the Morris water maze. Premarin improved early spatial learning and memory in nulliparous rats but impaired early learning in primiparous rats. With training, primiparity increased hippocampal neurogenesis, and Premarin decreased immature neurons, regardless of parity. Moreover, Premarin increased serum tumor necrosis factor α and the CXC chemokine ligand 1 (CXCL1) in trained nulliparous, but not primiparous, rats. However, Premarin decreased the expression of the immediate early gene zif268 in the dorsal CA3 region in primiparous rats after training. Thus, primiparity alters how Premarin affects spatial learning, neuronal activation, and serum cytokines. These findings have implications for the treatment of age-associated cognitive decline in women.

Objective: Adults with acquired brain injury (ABI) often experience memory impairments that are persistent and difficult to treat. Although evidence has shown that rehabilitation programs may improve cognitive performance in persons with ABI, there is an opportunity to look more closely at the benefits provided by specific interventions. We conducted a systematic review and meta-analysis to evaluate whether compensation-based memory programs improve memory or everyday outcomes (e.g., mood, quality of life, community integration, everyday functioning). Method: The review was limited to published, Englishlanguage controlled trials that evaluated compensatory memory interventions for adults (18+) with ABI using at least one memory or everyday outcome. The final search was conducted in April 2021 using PsychINFO, Medline, EMBASE, the Cochrane Review database, Google Scholar, and the reference lists of relevant articles. Results: Of 2,817 identified articles, 22 controlled trials met inclusion criteria, of which 12 provided sufficient data to include in the meta-analyses. Risk of bias assessment identified problems with recruitment and masking procedures. Results indicate that compared to controls, these interventions produce positive effects on outcomes of immediate verbal recall (g = 0.43), participant-reported memory (g = 0.28), and strategy use (g = 0.39) and that these improvements are maintained at follow-up. Conclusions: Compensatory memory programs produce meaningful memory improvements and are a promising avenue for reducing ABI-related memory impairment. Future research focusing on specific subsets of ABI populations and a broader range of participant-reported outcomes is needed. This review was preregistered in the PROSPERO database (Registration number: CRD42020197592).