Fereshteh Farajdokht ¹ Craig Myrum ² Clive R Bramham ³ Akash Gautam ^4*

• ¹ Tabriz University of Medical Sciences, Tabriz, Iran
• ² Loyola University Maryland, Baltimore, Maryland, United States
• ³ University of Bergen, Bergen, Hordaland, Norway
• ⁴ University of Hyderabad, Hyderabad, India

Aging is often accompanied by declines in cognitive function and behavior. These changes include subtle deficits in memory to the devastating effects of Alzheimer’s disease (AD) and substantial inter-individual variability in gait function among older adults. Not only do such differences exist between individuals, but many age-related health outcomes, vulnerabilities, and therapeutic responses also vary by sex and gender. This topic highlights some of these differences to advance our understanding of the complex interplay between sex, gender, hormones, and other factors in neurocognitive aging and behavior. The cross-sectional study by Ma et al. was conducted to examine the prevalence and risk factors of subjective cognitive decline (SCD) among 1,120 older adults aged 60+. The study demonstrated a high prevalence of SCD in this population, with 37.9%. Numerous risk factors for SCD were identified, such as advanced age, obesity, long-term smoking, coronary heart disease, visual impairment, vegetarian diet, average sleep duration less than 6 hours per night, unmarried status, and residing in a rural region. Gender-based analysis revealed statistically significant differences in SCD prevalence across marital status, dietary habits, sleep duration, smoking, drinking, and hypertension. Given the higher prevalence of SCD in rural populations compared to urban ones, it suggests that socio-cultural influences, such as lower educational attainment and reduced opportunities for cognitive engagement, may contribute to diminished cognitive reserve and increased vulnerability to cognitive deterioration. These results underscore the substantial cognitive health challenges that the elderly encounter and offer valuable insights for the development of public health strategies and targeted interventions. The study underscores the significance of early screening and prevention programs, as well as the potential advantages of fostering physical activity and social engagement in the preservation of cognitive health in geriatric populations. Sex differences were also observed in the study by Wang et al. where men displayed a greater degree of age-related cerebellar atrophy than women. The authors utilized convolutional neural networks to segment the cerebellum into 28 subregions and measured subregional volumes and shape analysis to measure cerebellar thickness. In addition to significant sex differences, the study supports earlier reports of region-specific changes in cerebellar volume, as well as region-specific rates of decline. Despite growing recognition of substantial sex differences in aging, including those described above, studies specifically focusing on the effects of aging in women are lacking. This research topic also includes studies that aim to address this gap in knowledge. The narrative review by Warren looks into the complex relationships between neuroinflammation, AD, and gender-specific dietary habits, emphasizing the substantial gender disparity in the prevalence and severity of AD. The research demonstrates that males have a preference for red and processed meats, while women tend to favor healthier options such as vegetables and whole grains. Additionally, the study identifies distinct dietary preferences and eating patterns between the genders. Additionally, women demonstrate increased morning appetite and more frequent snacking. The review suggests that these gender-specific dietary practices may contribute to neuroinflammatory states that influence the pathogenesis of AD. The study offers valuable insights into the potential impact of diet on neuroinflammation and risk of AD by investigating a variety of factors that influence dietary choices, including biological, psychological, sociocultural, and socioeconomic influences. The significance of gender Finally, in the paper by Nerattini et al. the authors note that while neuroprotective effects of estrogen are well-documented in women, the effect of menopausal hormone therapy on AD risk reduction is less clear. To that end, they carried out a large meta-analysis of randomized controlled trials and observational studies. Their stratified analysis estimated a 32% reduced risk of dementia with midlife estrogen therapy alone, while estrogen-plus-progesterone therapy was less effective, as was late-life hormone therapy. Together this collection of studies serves to illustrate the wide impacts of sex and gender on neurocognitive aging and behavior and underscores the knowledge gaps and challenges in this still-emerging field.