Divergent patterns of cognitive deficits and structural brain alterations between older adults in mixed-sex and same-sex relationships

Data availability statement: Publicly available datasets were analyzed in this study. These data can be found at: https://naccdata.org/.Copyright © 2022 Manca, Correro, Gauthreaux and Flatt. Background: Sexual minority (SM) older adults experience mental health disparities. Psychiatric disorders and neuropsychiatric symptoms (NPS) are risk factors for cognitive decline. Although older people in same-sex (SSR) compared to mixed-sex relationships (MSR) perform more poorly on cognitive screening tests, prior studies found no differences in rates of dementia diagnosis or neuropsychological profiles. We sought to explore the role of NPS on neurocognitive outcomes for SM populations. We compared cognitive performance and structural brain parameters of older adults in SSR and MSR. Methods: Data were originally collected at Alzheimer's Disease Research Centers (ADRCs). Inclusion criteria were: age of 55+ years, a study partner identified as a spouse/partner, and availability of T1-MRI brain volumes/thickness. Participants were labeled as either SSR or MSR based on their/their co-participant's reported sex. We identified 1,073 participants (1,037 MSR−555 cognitively unimpaired [CU]; 36 SSR−23 CU) with structural MRI data, Mini-Mental State Exam (MMSE), and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores. A subset of the overall sample completed comprehensive neuropsychological assessment (n = 939; 908 MSR−494 CU; 31 SSR−22 CU). Covariates included in statistical models were age, sex, education, total intracranial volume, and apolipoprotein E genotype. Results: Multivariate general linear models showed significant diagnosis-by-relationship interaction effects on the left parahippocampal gyrus volume. After stratification by relationship group, only cognitively impaired (CI) MSR had significantly smaller left parahippocampal volumes than MSR-CU. The SSR group showed better episodic memory performance. Severity of neuropsychiatric symptoms was negatively associated with volume/thickness of bilateral fronto-temporal areas and with MMSE scores, predominantly in the MSR group. Conclusion: In our study, MSR participants presented with a more compromised cognitive profile than SSR participants. MSR-CI participants showed significantly smaller left medio-temporal volumes, a neural signature of AD. Neuropsychiatric symptoms predicted smaller fronto-temporal volumes in the MSR more consistently than in the SSR group. These findings may be due to unexplored protective factors against cognitive decline in SM elders. Indeed, social support has been proposed as a protective factor warranting future investigation.K01AG056669 and R24AG066599 (JF). The NACC database was funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD)

Designing programmes of physical activity through sport: Learning from a widening participation intervention, 'City of Football'

Background: Implementation profoundly influences how well new audiences engage with sport-based physical activity programmes. Recognising that effective implementation relies on concurrently generating supportive contexts, systems and networks for the least engaged ‘target’ groups; this paper aims to address what underpins children’s (non) engagement with football-based physical activity. Methods: An observational research design, using a non-probability sample of N=594 primary and secondary schoolchildren assessed outcomes of a three-year ‘City of Football’ (CoF) programme. Pupils self-reported football participation, personal friendship networks and exposure to six concurrent sources of influence (SoI). A 2-step hierarchical cluster analysis and univariate analyses assessed between-cluster differences. Results: Girls played football least regularly (χ2 [4] = 86.722, p = 0.000). Overall, participation was significantly associated with personal networks engaged in football. Boys’ personal networks were more stable and structurally effective. Football participation was also positively and linearly association with SoI scores. Girls and pupils with no personal networks around football reported the lowest SoI scores. Three clusters emerged, dominated by social network influences. The Traditional Market (n=157, 27.7%) comprised 81.7% boys; they regularly played football, had the most effective network structure and scored highly across all six domains of SoI. The Sporadically Engaging Socialisers (n=190, 33.5%) comprised 52.9% girls who rarely played football, reported low SoI scores and an inferior network structure. In the Disconnected cluster (n=220, 38.8%), 59.3% were non-footballing girls who reported the lowest motivation and ability SoI scores; and no personal networks engaged in football. Conclusions: This study reveals new insights about the primacy of social network effects for engaging children in football-based physical activity programmes. With little or no attention to these social-oriented issues, such interventions will struggle to attract ‘target’ children, but will readily engage already well-connected, experienced football-playing boys. The challenge for drawing non-footballing children into football-based interventions lies with engaging children – especially girls - whose social networks are not football-focused, while they also find football neither personally motivating nor easy to do

Mating alters gene expression patterns in Drosophila melanogaster male heads

<p>Abstract</p> <p>Background</p> <p>Behavior is a complex process resulting from the integration of genetic and environmental information. <it>Drosophila melanogaster </it>rely on multiple sensory modalities for reproductive success, and mating causes physiological changes in both sexes that affect reproductive output or behavior. Some of these effects are likely mediated by changes in gene expression. Courtship and mating alter female transcript profiles, but it is not known how mating affects male gene expression.</p> <p>Results</p> <p>We used <it>Drosophila </it>genome arrays to identify changes in gene expression profiles that occur in mated male heads. Forty-seven genes differed between mated and control heads 2 hrs post mating. Many mating-responsive genes are highly expressed in non-neural head tissues, including an adipose tissue called the fat body. One fat body-enriched gene, <it>female-specific independent of transformer </it>(<it>fit</it>), is a downstream target of the somatic sex-determination hierarchy, a genetic pathway that regulates <it>Drosophila</it> reproductive behaviors as well as expression of some fat-expressed genes; three other mating-responsive loci are also downstream components of this pathway. Another mating-responsive gene expressed in fat, <it>Juvenile hormone esterase </it>(<it>Jhe</it>), is necessary for robust male courtship behavior and mating success.</p> <p>Conclusions</p> <p>Our study demonstrates that mating causes changes in male head gene expression profiles and supports an increasing body of work implicating adipose signaling in behavior modulation. Since several mating-induced genes are sex-determination hierarchy target genes, additional mating-responsive loci may be downstream components of this pathway as well.</p

Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p

The effect of dietary restriction on reproduction: a meta-analytic perspective

Background: Dietary restriction (DR), a reduction in the amount of food or particular nutrients eaten, is the most consistent environmental manipulation to extend lifespan and protect against age related diseases. Current evolutionary theory explains this effect as a shift in the resolution of the trade-off between lifespan and reproduction. However, recent studies have questioned the role of reproduction in mediating the effect of DR on longevity and no study has quantitatively investigated the effect of DR on reproduction across species. Results: Here we report a comprehensive comparative meta-analysis of the effect of DR on reproduction. In general, DR reduced reproduction across taxa, but several factors moderated this effect. The effect of DR on reproduction was greater in well-studied model species (yeast, nematode worms, fruit flies and rodents) than non-model species. This mirrors recent results for longevity and, for reproduction, seems to result from a faster rate of decline with decreasing resources in model species. Our results also suggested that not all reproductive traits are affected equally by DR. High and moderate cost reproductive traits suffered a significant reduction with DR, but low cost traits, such as ejaculate production, did not. Although the effect of DR on reproduction was stronger in females than males, this sex difference reduced to near zero when accounting for other co-factors such as the costliness of the reproductive trait. Thus, sex differences in the effect of DR on longevity may be due to a failure to expose males to as complete a range of the costs of reproduction as females. Conclusions: We suggest that to better understand the generality of the effect of DR, future studies should attempt to address the cause of the apparent model species bias and ensure that individuals are exposed to as many of the costs of reproduction as possible. Furthermore, our meta-analytic approach reveals a general shortage of DR studies that record reproduction, particularly in males, as well as a lack of direct side-by-side comparisons of the effect of DR on males and females

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Is evolvability evolvable?

In recent years, biologists have increasingly been asking whether the ability to evolve — the evolvability — of biological systems, itself evolves, and whether this phenomenon is the result of natural selection or a by-product of other evolutionary processes. The concept of evolvability, and the increasing theoretical and empirical literature that refers to it, may constitute one of several pillars on which an extended evolutionary synthesis will take shape during the next few years, although much work remains to be done on how evolvability comes about