Two separate, large cohorts reveal potential modifiers of age-associated variation in visual reaction time performance.

To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (ntotal = 75,666, nwomen = 47,700, nmen = 27,966; ages 18-85 years old, mean (M)Age = 46.54, standard deviation (SD)Age = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (ntotal = 158,249 nwomen = 89,333 nmen = 68,916; ages 40-70 years old, MAge = 55.81, SDAge = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (ntotal = 39,795, nwomen = 29,640, nmen = 10,155; ages 40-70 years old, MAge = 56.59, SDAge = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.

Smoking is associated with impaired verbal learning and memory performance in women more than men.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.

An update on the cognitive impact of clinically-used hormone therapies in the female rat: models, mazes, and mechanisms.

In women, ovarian hormone loss associated with menopause has been related to cognitive decline. Hormone therapy (HT) may ameliorate some of these changes. Understanding the cognitive impact of female steroids, including estrogens, progestogens, and androgens, is key to discovering treatments that promote brain health in women. The preclinical literature has presented elegant and methodical experiments allowing a better understanding of parameters driving the cognitive consequences of ovarian hormone loss and HT. Animal models have been a valuable tool in this regard, and will be vital to future discoveries. Here, we provide an update on the literature evaluating the impact of female steroid hormones on cognition, and the putative mechanisms mediating these effects. We focus on preclinical work that was done with an eye toward clinical realities. Parameters that govern the cognitive efficacy of HT, from what we know thus far, include but are not limited to: type, dose, duration, and route of HT, age at HT initiation, timing of HT relative to ovarian hormone loss, memory type examined, menopause history, and hormone receptor status. Researchers have identified intricate relationships between some of these factors by studying their individual effects on cognition. As of late, there is increased focus on studying interactions between these variables as well as multiple hormone types when administered concomitantly. This is key to translating preclinical data to the clinic, wherein women typically have concurrent exposure to endogenous ovarian hormones as well as exogenous combination HTs, which include both estrogens and progestins. Gains in understanding the parameters of HT effects on cognition provide exciting novel avenues that can inform clinical treatments, eventually expanding the window of opportunity to optimally enhance cognition and brain health in aging women. This article is part of a Special Issue entitled Hormone Therapy.