Cognition In Men Research Articles

Metformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men

BackgroundAn altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D. AimTo investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. MethodsWe explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (n = 172); (2) people with long-term T2D on metformin monotherapy (n = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (n = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (n = 22). Analyses were also performed stratifying by sex. ResultsSeveral bacterial species belonging to the Proteobacteria (Escherichia coli) and Verrucomicrobia (Akkermansia muciniphila) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (Romboutsia timonensis, Romboutsia ilealis) were negatively associated. Due to the consistent increase in A. muciniphila and decrease in R.ilealis in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the A.muciniphila/R.ilealis ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the A.muciniphila/R. ilealis ratio was significantly and positively associated with higher memory scores and improved memory in men.Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved in arginine metabolism, especially in production of glutamate (astA, astB, astC, astD, astE, putA), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate. ConclusionsThe beneficial effects of metformin may be mediated by changes in the composition of the gut microbiota and microbial-host-derived co-metabolites.

A Pilot Study on Sex Hormones and Cognition in Men with Multiple Sclerosis

A Pilot Study on Sex Hormones and Cognition in Men with Multiple Sclerosis

Intake of dark green vegetables may benefit specific cognitive domains in US men and women aged 60 years or older

BACKGROUND: The prevalence and relationship between dark green vegetables (DGV) and specific cognitive domains in the aging US population are not well-established for men and women. OBJECTIVE: To explore the associations between DGV, its bioactive nutrients, and cognitive function, including its specific domains, and whether they differ by sex METHODS: The study analyzed a cross-sectional sample of 2,793 US adults aged 60 or older from the 2011–2014 NHANES. DGV was dichotomized, and bioactive nutrients were divided into quartiles. Weighted linear regressions were used to analyze the association between DGV, bioactive nutrients, and standardized cognitive function scores, including specific domains (CERAD, DWR, AFT, DSST), while controlling for covariates. The study also tested for sex-based effect modification RESULTS: Overall, 61.7% of participants reported no DGV intake, and men reported no DGV intake more frequently than women (67.8 vs.56.5%, p < 0.001). DGV was associated with overall cognitive function(β= 0.10, p = 0.024) and by its specific domains: memory-related i.e., learning and remembering (CERAD:β= 0.10, p = 0.015; DWR:β= 0.10, p = 0.010), marginally associated with executive function (AFT:β= 0.10, p = 0.075), but not with problem-solving(DSST:β= 0.03, p = 0.587). Although the associations between bioactive nutrients and specific cognitive domains were mixed, a higher intake of these nutrients was still linked to higher overall cognitive function. Only β-carotene and its associations with overall cognitive and AFT were modified by sex. CONCLUSION: The majority of US older adults (>60%) lack DGV in their diet. Intake of DGV, which is rich in phylloquinone, β-carotene, and α-tocopherol, may benefit certain domains of cognition in men and women, such as learning and memory

Hypertension differentially impacts cognition in men and women in early midlife.

The current study aimed to understand how sex differences in the timing of hypertension onset contribute to early midlife risk for cognitive decline that may differ by sex and whether sex-dependent advantages in normotensive populations are influenced by the presence of hypertension. One hundred and ninety-five adults aged 45-55 from the New England Family Study underwent neuropsychological testing to assess attention, executive function, and memory. Physician-diagnosed hypertension status was self-reported via questionnaire. Mid-adulthood hypertension was associated with worse performance on measures of attention and memory, but the cognitive domains impacted varied by sex. Hypertension was associated with only attention in men, whereas in women it was associated with attention and associative and working memory. Sex differences in midlife cognitive performance found in normotensive adults were attenuated in those with hypertension. Our results underscore the importance of accounting for sex when assessing the impact of hypertension on midlife cognition that could be indicative of later decline and risk for cognitive impairment and dementia, given hypertension is an independent risk factor.

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults.

IntroductionExcitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex.MethodsNinety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning.ResultsIn the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions.ConclusionGreater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association.

Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial

ObjectivesThe aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and...

Pilot trial of physical and cognitive changes related to fall risk in enzalutamide patients with castration-resistant prostate cancer (CRPC).

e17018 Background: Advanced prostate cancer disproportionally affects older men (age ≥ 75 years). Despite representing only 26% of diagnoses, older men represent half of those diagnosed with metastatic disease and half of all prostate cancer deaths. Treatment options for CRPC include enzalutamide (enza), a competitive inhibitor of the androgen receptor, which shows improved overall survival and other cancer-specific responses in older men. However, enza is also reportedly associated with increased fall frequency of unclear pathophysiology. This pilot study examines strength, balance, and cognition in men before and 12 weeks after starting enza therapy for CRPC. Methods: This prospective single-arm study included men about to begin enza for CRPC, ≥ 65 years, able to ambulate independently. The following tests were administered at baseline and 12 weeks after initiation of enza: Sit-to-stand test (STS), Timed-Up-and-Go test, proprioception assessment, computerized dynamic posturography including sensory organization test (SOT), motor control test (MCT), and limits of stability; Functional Assessment of Cancer Therapy-Prostate, BPI-SF, Activities-specific Balance Confidence (ABC), Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire (IPAQ), and the Godin leisure-time exercise questionnaire (GLTEQ). Falls were assessed with self-report fall diaries and calls from study team to participants over the course of 12 months. Results: Twenty-five participants enrolled. Median age was 75 years. There were 23 (92%) with both baseline and 12-week assessments, and 21 (84%) participants had complete falls data. From baseline to the 12-week follow up, ABC scale scores decreased (median 90.4 to 85.2), GLTEQ scale scores decreased (median 31.4 to 28.0), and time sitting per day from IPAQ increased (4 hours to 5 hours). Of those evaluable for falls, 15 (71%) did not fall during the 12 months and 6 (29%) fell at least once. The fallers and non-fallers did not differ with respect to age or MoCA scores at baseline and on re-assessment. Those who fell performed more poorly on the STS test, the ABC and the dynamic posturography evaluations. Those who fell also had a higher level of activity by GLTEQ. Conclusions: This pilot study does not clearly elucidate the pathophysiology of falls in older men with CRPC taking enza but does provide useful and important guidance for the design of future studies in this area. Baseline and 12-week testing should be repeated at the 24-week time-point to allow for sufficient exposure to enza. To avoid confounding by practice effects, physical tests, particularly dynamic posturography, should be performed at least once prior to baseline assessment. Further research is needed to understand the mechanisms underlying the increased risk of falls previously observed in older men with CPRC taking enza.

Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial.

Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. Randomized trial of transdermal estradiol 0.9 mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory, and spatial problem solving over time. Men receiving androgen deprivation therapy (ADT) for prostate cancer. Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, Month 1, Month 3, and Month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Seventy-eight participants were randomized. Baseline mean scores were 21.0 (standard deviation [SD] 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (SD 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% confidence interval [CI] -1.2 to 2.5), p = .36, or the GML, MAD -3.2 (95% CI -12.0 to 5.6), p = 0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by the administration of estradiol.

Social Disengagement and Cognitive Function: Does the Association Vary by Gender?

Although social disengagement is considered to be a predictor of cognitive decline, and increase risk of Alzheimer’s and related dementias, little is known regarding the gender-specific association between social disengagement and cognition among Korean middle-aged and older adults. Korea’s Confucianism-based gender roles provide unique contexts to examine gender differences in the influence of social disengagement on cognition. This study investigated the association between social disengagement and cognitive function in a nationally representative sample of Koreans aged 45 years or older (N = 5,196 women and 2,707 men), using data from the Korean Longitudinal Study of Aging (2008-2018). Results from the generalized estimating equation model showed that compared to consistent social engagement, consistent non-engagement was significantly associated with lower cognitive function among both genders. Transitioning from social engagement to non-engagement was significant for males only. Of various types of social activities (religious, senior center, sport, reunion, voluntary, political), consistent non-engagement in a senior center was most associated with lower cognitive function among both genders, while consistent non-engagement in religious activities was significant for females only. While household arrangements were not associated with cognition in men, widowed women had increased risk of cognitive decline than married women, as did women living in households of three or more people. Depression was a predictor of cognitive decline among males only. In this gender-specific study, we found that consistent participation in social activities, especially via membership in a senior community center, is beneficial in preventing cognitive decline among both genders.

Gender differences in the moderating capacity of reserve and resilience factors on the association of Alzheimer’s disease brain pathology and cognitive function

AbstractBackgroundIn the context of ageing and Alzheimer’s disease (AD), factors linked to reserve and resilience may confer protection against impact of underlying neuropathology on cognitive function. Such factors are differentially manifested in men and women, yet limited studies have explored potential divergence in their capacity to moderate cognitive outcomes, particularly within at‐risk preclinical populations. Here we evaluate gender dichotomies in the effect modification of independent brain and cognitive reserve factors on associations of AD‐related neuropathology and cognition.MethodGender‐stratified analysis of CHARIOT:PRO SubStudy data (2,451 preclinical older adults: 60‐85 years, screened at Imperial College London and University of Edinburgh) was performed using a‐priori confounder‐adjusted linear regression models. The effect modifying role of brain (intracranial volume) and cognitive (educational attainment, estimated premorbid‐intelligence: epIQ, physical activity) reserve proxies on the associations of AD neuropathology (brain amyloid load: via PET/CSF Aβ42; and hippocampal volumes: structural MRI) with multidomain cognitive performance (assessed via learning effect [i.e. difference in initial administration and baseline scores – median 3.5 months] on the Repeatable Battery Assessment of Neuropsychological Status‐RBANS) were independently examined in men and women.ResultLearning effects were negatively modulated by amyloid positivity and male gender. Larger hippocampal volumes predicted better global cognition in men, and better immediate memory for both men and women (All P‐values<0.05). In mutually adjusted models (additionally accounting for age and ApoE), education and physical activity modified the effects of amyloid positivity on cognition, while epIQ moderated associations with hippocampal volume. The moderation was more pronounced for highly physically active men (β=7.7; p=0.04) and marginally for women educated to Bachelors’ level (β=5.9; p=0.06). Above‐median epIQ moderated associations of hippocampal volume with global cognition only in women (β=0.0003; p=0.03). Adjustment for BMI, smoking, blood pressure and diabetes had no remarkable effect on the results.ConclusionWe noted differential effects of cognitive reserve in men and women supporting the importance of accounting for sex/gender divergence when exploring moderators of AD‐related neuropathology on function. Further research into mechanisms underlying sex/gender differences in preservation and maintenance of cognitive function are warranted for personalised strategies towards increasing neurocognitive resilience and delaying transitions to more severe clinical states.

Discrimination impairs cognitive function in ageing men and women

Abstract Background We sought to assess changes in episodic memory and executive functioning among men and women in the Midlife in the United States (MIDUS) cohort study; and to delineate variations in episodic memory and executive functioning by gender; and to determine the impact of discrimination on longitudinal changes in episodic memory and executive functioning. Methods We used data from the MIDUS study - a national probability sample of non-institutionalized, English speaking respondents aged 25-74 living in the 48 contiguous states of the United States. The initial wave in our study (1995) included 4963 non-institutionalized adults aged 32 to 84 (M = 55, SD = 12.4). Dependent variables are episodic memory and executive functioning, assessed with the Brief Test for Cognition. The independent variables were discrimination (lifetime and daily discrimination) variables. Furthermore, we investigated baseline cognition score, race/ethnicity (White, Hispanic, other), education (some college or more vs high school of less), whether or not living with partner, income (per 100% above Federal Poverty Level), unemployed (vs employed), retired (vs employed), physical health (self-reported), vigorous physical activity, depression (continuous scale), anxiety (continuous scale). To assess cognition changes we estimated adjusted linear regression models. Results Cross-sectional, work discrimination was associated with cognition in men and women. Longitudinally, adjusting for baseline cognition score, race/ethnicity, education, living situation, income, (un)employed, (not)retired, physical health, vigorous physical activity, depression, and anxiety, we found an association of family strain with cognition changes in high-income men, and an association of daily discrimination with cognition changes in men (Beta 0.01, P-value: 0.001). Conclusions Reducing discrimination might be an important measure to support cognitive function in ageing populations.

Multimodal neuroimaging markers of variation in cognitive ability in older HIV+ men.

This study used converging methods to examine the neural substrates of cognitive ability in middle-aged and older men with well-controlled HIV infection. Seventy-six HIV+ men on antiretroviral treatment completed an auditory oddball task and an inhibitory control (Simon) task while time-locked high-density EEG was acquired; 66 had usable EEG data from one or both tasks; structural MRI was available for 43. We investigated relationships between task-evoked EEG responses, cognitive ability and immunocompromise. We also explored the structural correlates of these EEG markers in the sub-sample with complete EEG and MRI data (N = 27). EEG activity was associated with cognitive ability at later (P300) but not earlier stages of both tasks. Only the oddball task P300 was reliably associated with HIV severity (nadir CD4). Source localization confirmed that the tasks engaged partially distinct circuits. Thalamus volume correlated with oddball task P300 amplitude, while globus pallidus volume was related to the P300 in both tasks. This is the first study to use task-evoked EEG to identify neural correlates of individual differences in cognition in men living with well-controlled HIV infection, and to explore the structural basis of the EEG markers. We found that EEG responses evoked by the oddball task are more reliably related to cognitive performance than those evoked by the Simon task. We also provide preliminary evidence for a subcortical contribution to the effects of HIV infection severity on P300 amplitudes. These results suggest brain mechanisms and candidate biomarkers for individual differences in cognition in HIV.

Do depressive symptoms link chronic diseases to cognition among older adults? Evidence from the Health and Retirement Study in the United States

BackgroundFew studies have assessed psychological pathways that connect the association between non-psychotropic chronic disease and cognition. We assessed the extent to which the association between the two was mediated by depressive symptoms in older adults. MethodsData came from waves 10–13 (2010–2016) of the Health and Retirement Study in the United States (7,651 men and 10,248 women). Multilevel path analysis, allowing for random intercepts and slopes, was employed to estimate the extent to which depressive symptoms mediated the total effect of a chronic disease on cognition. ResultsWe found that the presence of stroke, high blood pressure, diabetes, heart problems, and comorbidity, in both men and women, and lung disease in women, was associated with lower levels of cognition. The total effects of chronic diseases on cognition were partially mediated through depressive symptoms. Depressive symptoms mediated approximately 19%–39% and 23%–54% of the total effects of chronic diseases on cognition in men and women, respectively. LimitationsWe relied on self-reported diagnoses of diseases and depressive symptoms. Our use of a multilevel path analysis with random slopes precluded the inclusion of binary/categorical dependent variables, and the estimation of standardized beta values. ConclusionsTo understand the cognitive challenges that chronically ill older adults face, practitioners and policymakers should consider not just the direct symptoms related to chronic diseases, but also the often overlooked psychological conditions faced by older adults.

Urinary Steroid Metabolome Signature is Associated With Cognitive Function in Older Adults

Abstract Background: Elevated urine cortisol (<1% of urinary steroid metabolome) was reported to predict future development of dementia. Our objective was to determine the association of urine steroid metabolome and its diurnal variation with cognitive function in men and women. Methods: Cross-sectional study of community-dwelling adults ≥ 50 years. Participants with adrenal disorders, end-stage renal or liver disease, on exogenous steroids or drugs affecting steroid metabolism were excluded. All participants completed day and night separate urine collection. A series of seven IPad-based tests using the National Institute of Health Toolbox Cognition Battery were administered to evaluate five key domains; performance was reported using fully corrected T-scores for age, sex, education, and race with a national normative mean of 50. T-scores were generated for the two summary measures: 1) fluid cognition (includes executive function, episodic memory, working memory, and processing speed), and 2) total composite (composite of fluid and language score). Urine samples were analyzed with the liquid-chromatography, high-resolution, accurate-mass mass spectrometry for 25 urine steroid metabolites. Results: Of 109 participants, 56 (51%) were women, and age and educational status were similar in men and women. On cognitive assessment, men and women had similar median composite cognition (T-score of 53 vs 54, p=0.74) and fluid cognition (T-score of 53 vs 51, p-value 0.96). Urine steroid metabolome analysis demonstrated 21/25 steroids were higher in men vs women. In both women and men, the ratio of total cortisol metabolites/total androgen metabolites (TCM/TAM) was associated with lower fluid cognition (women: ρ= -0.34, p=0.01, men: ρ= -0.43, p=0.001) and composite cognition (women: ρ= -0.27, p=0.04, men: ρ= -0.39, p=0.004). Higher ratio of day to night TCM were associated with a better fluid cognition in men (ρ= 0.35, p=0.01), but not in women (ρ= -0.11, p=0.41). Steroid ratios suggesting a relative enzymatic deficiency of 5α-Reductase type 2 was associated with lower fluid cognition in women (ρ= -0.29, p=0.03). In men, the fluid composite score was associated with a relative deficiency in 21-Hydroxylase (ρ= 0.42, p=0.002), 3β-Hydroxysteroid dehydrogenase (ρ= 0.43, p=0.001), and P450oxidoreductase (ρ= -0.35, p=0.01). Conclusion: We showed that a higher glucocorticoid to androgen ratio and a flattened circadian steroid variation were associated with lower global and fluid cognition score. Steroid ratios reflecting steroidogenesis enzymatic activity demonstrated sex differences in relation to cognition. Additional studies should examine whether the steroid fingerprint associated with lower cognition is predictive of a future dementia onset.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men.

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators.Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50–70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)].Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits.Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.

Predicting cognitive function based on physical performance: findings from the China Health and Retirement Longitudinal Study.

Physical performance tests are simple means of predicting an individual's risk of cognitive decline. This study aimed to assess the predictive value of physical performance tests and develop predictive models for cognitive function. Cognitive function was tested biennially and calculated for mental intactness, episodic memory, and global cognition. Using a generalized estimating equation (GEE), we examined each baseline physical performance test as a predictor of cognitive decline. Using a multivariate linear regression model (MLRM), we developed predictive models for cognitive function. Bland-Altman analysis was performed to analyze the agreement between estimated and measured cognition. We validated the predictive model internally with 1000 bootstrap resamples. Better physical performance test results, except for standing balance, were associated with a slower cognitive decline over time and better cognitive function at follow-up. Regarding the predictive models, all physical performance tests were included in men; only five chair stands test was included in women. Bland-Altman analysis showed that measured cognition was equivalent to estimated cognition in men (mean bias, 0; 95% limits of agreement, - 8.56 to 8.56) and women (mean bias, 0; 95% limits of agreement - 8.79 to 8.7). Bootstrap analysis showed that predictors were selected in 78.4-100% for men and 64.5-100% for women. Bland-Altman and bootstrap analysis demonstrated good agreement and stability of the predictive models. Physical performance tests are simple, easily obtainable, and clinically relevant markers for cognitive function with aging; predictive models based on physical performance can be used to predict cognitive function.

Gender differences in the association of childhood socioeconomic status and late‐life cognition among African Americans: Findings from the STAR study

AbstractBackgroundLow socioeconomic status in childhood has been linked with poor cognitive function in old age. But few studies have focused on African Americans or evaluated gender differences. We examined cross‐sectional associations of childhood socioeconomic factors with late‐life cognition and effect modification by gender.MethodsStudy of Healthy Aging in African Americans (STAR) participants were 722 African Americans (69% women; mean age = 68.4 and education: 60% <High school) community‐residing long‐term members of Kaiser Permanente Northern California. Summary scores in 3 cognitive domains (executive function, semantic memory, verbal memory) and a global cognition composite were based on the Spanish and English Neuropsychological Assessment Scales (SENAS). Participants rated frequency of experiencing hunger as a child (sometimes/often vs. rarely/never), their family’s financial status (average/high vs. poor), and parental education (>= high school vs. < high school), as indicators of childhood SES. Linear regression models adjusted for age were used to examine childhood SES and late‐life cognition, and effect modification by gender.ResultsThere were no gender differences in experiencing childhood hunger (p=.08), having poor family finances (p=0.30), or parental education (p=0.17). In the pooled model with women and men, higher frequency of childhood hunger was associated with worse cognition overall (β=‐0.36, 95% CI=‐0.66, ‐0.06) and in all domains (executive: β=‐0.32, 95% CI=‐0.63, ‐0.01; semantic: β=‐0.38, 95% CI=‐0.53, ‐0.23; verbal: β=‐0.42, 95% CI=‐0.73, ‐0.12). Low parental education was only associated with lower global cognition β=‐0.18, 95% CI=‐0.33, ‐0.02 and semantic memory (β=‐0.40, 95% CI=‐0.57, ‐0.23). Childhood family financial status was not associated with late‐life cognition. In gender‐stratified models, women who reported greater frequency of childhood hunger had worse cognition in every domain except semantic memory (overall: β=‐0.53, 95% CI=‐0.94, ‐0.13; executive: β=‐0.61, 95% CI=‐1.01, ‐0.20; semantic: β=‐0.21 95% CI=‐0.64, 0.21; verbal: β=‐0.46, 95% CI=‐0.87, ‐0.06). In contrast, childhood hunger was not associated with cognition in men (overall: β=‐0.14, 95% CI=‐0.59, 0.32; executive: β=0.11, 95% CI=‐0.35, 0.58; semantic: β=‐0.05 95% CI=‐0.57, 0.48; verbal: β=‐0.40, 95% CI=‐0.88, 0.08), but low parental education was associated with semantic memory (β=‐0.43, 95% CI=‐0.73, ‐0.14).ConclusionChildhood hunger is associated with worse cognition in old age, particularly among women.

Role of testosterone in cognition and mobility of aging men.

Cognitive decline and impairment of physical performance and mobility are age-related clinical problems with major negative impact on quality of life of elderly men. In how far the decline of testosterone production contributes to these problems in older men and whether testosterone therapy can contribute to slow down, prevent, or reverse their development remains subjects of debate. This narrative review presents the current knowledge on association of sex steroid status with cognitive decline and impairment of physical function and mobility in elderly men and on the effects of testosterone therapy on cognition and on physical performance and mobility in elderly men. The review is based on electronic database searches with primary focus on evidence from larger prospective observational studies and from controlled randomized trials, respectively. In most observational studies, testosterone levels do not predict cognitive decline or development of Alzheimer's disease. In randomized trials, testosterone therapy did not significantly affect cognition in men with low or low-to-normal serum testosterone, regardless of whether they have preexisting cognitive impairment. Overall, observational data indicate that the usually moderate decline of androgen exposure in older men cannot fully account for the parallel decline of physical performance and mobility. Trials of testosterone therapy in older men with low or low-normal serum testosterone, whether they were generally healthy or suffered from physical function impairments, either did not show any effect on mobility and physical performance or showed limited effects of uncertain clinical relevancy. The whole of the evidence tends to downplay the role of sex steroid status in the decline of cognitive function and impairment of physical function and mobility in older men. Based on the available evidence, prevention or treatment of cognitive decline or of impairment of mobility and physical function are not valid indications for testosterone treatment in older men with low or low-to-normal serum testosterone levels.

Ageing and cognition in men with fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The aim of our longitudinal study was to describe ageing-related cognitive changes in men with FXS. A neuropsychologist determined the raw scores (RSs) of 19 men with FXS twice with the Leiter International Performance Scale at an average interval of 22years. The ages of the participants at baseline ranged from 16 to 50 (mean 27) years. At follow-up, the RSs improved in two men, remained the same in two men and declined in 15 men. Overall, the RS of the study group deteriorated by an average 4 points in RSs (p<.001). Cognitive ageing in men with FXS started earlier than that in men in the general population; in many cases, cognitive ageing in men with FXS began before middle age, usually without any medical or other underlying cause.

Timing of peripubertal steroid exposure predicts visuospatial cognition in men: Evidence from three samples

Experiments in male rodents demonstrate that sensitivity to the organizational effects of steroid hormones decreases across the pubertal window, with earlier androgen exposure leading to greater masculinization of the brain and behavior. Similarly, some research suggests the timing of peripubertal exposure to sex steroids influences aspects of human psychology, including visuospatial cognition. However, prior studies have been limited by small samples and/or imprecise measures of pubertal timing. We conducted 4 studies to clarify whether the timing of peripubertal hormone exposure predicts performance on male-typed tests of spatial cognition in adulthood. In Studies 1 (n = 1095) and 2 (n = 173), we investigated associations between recalled pubertal age and spatial cognition in typically developing men, controlling for current testosterone levels in Study 2. In Study 3 (n = 51), we examined the relationship between spatial performance and the age at which peripubertal hormone replacement therapy was initiated in a sample of men with Isolated GnRH Deficiency. Across Studies 1–3, effect size estimates for the relationship between spatial performance and pubertal timing ranged from.−0.04 and −0.27, and spatial performance was unrelated to salivary testosterone in Study 2. In Study 4, we conducted two meta-analyses of Studies 1–3 and four previously published studies. The first meta-analysis was conducted on correlations between spatial performance and measures of the absolute age of pubertal timing, and the second replaced those correlations with correlations between spatial performance and measures of relative pubertal timing where available. Point estimates for correlations between pubertal timing and spatial cognition were −0.15 and −0.12 (both p < 0.001) in the first and second meta-analyses, respectively. These associations were robust to the exclusion of any individual study. Our results suggest that, for some aspects of neural development, sensitivity to gonadal hormones declines across puberty, with earlier pubertal hormone exposure predicting greater sex-typicality in psychological phenotypes in adulthood. These results shed light on the processes of behavioral and brain organization and have implications for the treatment of IGD and other conditions wherein pubertal timing is pharmacologically manipulated.