Search Results (191)

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

Background/Objectives: A growing body of literature has demonstrated that living with food insecurity (FI) increases risk for mental health concerns in addition to nutritional deficits (e.g., suboptimal micronutrient consumption, excessive macronutrient consumption, malnutrition). Yet, research is needed to improve our understanding of subpopulations potentially at increased risk for mental health concerns when living in the context of FI. The current study examined psychosocial health across women of different developmental life stages all living with FI. Methods: Female clients of a large, urban food bank (N = 680) living with FI completed measures of mental health and health-related quality of life (HRQOL) in a cross-sectional design conducted on site at the food bank. Results: Consistent with past research, FI severity was correlated with poorer psychosocial health across all variables. A multivariate analysis of covariance compared women living with FI across 4 developmental life stages (young adult, early midlife, late midlife, and older adult; age range = 18–94 years), controlling for FI severity and race/ethnicity, on outcomes related to mental health and HRQOL. Women in early and late midlife reported higher anxiety, eating disorder symptoms, and eating-related psychosocial impairment than younger and older women. Conclusions: The mental health toll of living with FI is profound; midlife may comprise a developmental period of increased vulnerability to experience this mental health burden of living with FI for women. Thus, efforts are needed to develop innovative pathways for interventions to support the mental health of midlife women living with FI, likely involving multi-level and/or multicomponent approaches to resource access. Full article

Background and Objectives: Body composition changes with aging and menopause, often leading to increased adiposity and a shift in fat distribution. While BMI is commonly used in clinical practice, it does not accurately reflect fat mass or distribution. This study aims to evaluate age-related changes in both total and regional adiposity using DXA-derived indices in Korean women aged ≥ 40 years and to assess the limitations of BMI-based obesity classification. Materials and Methods: This retrospective multicenter study analyzed the DXA scans and clinical records of 914 Korean women aged 40–80 years who attended menopause clinics across multiple institutions between 2018 and 2021. We analyzed five adiposity indices: body mass index (BMI), total body fat percentage (TB%F), fat mass index (FMI), visceral adipose tissue (VAT) area, and android-to-gynoid (A/G) fat ratio. Excess adiposity was defined as BMI ≥ 23 kg/m², TB%F ≥ 40%, FMI ≥ 9 kg/m², VAT > 100 cm², or A/G ratio > 1.0. Age group comparisons were made using ANOVA, and misclassification was assessed by comparing BMI with other indices. Results: Mean BMI increased with age, peaking in the 60s before declining in the 70s. TB%F and FMI peaked in the 50s, while VAT and A/G ratio increased continuously with age. Excess adiposity was found in 41.9% of women by TB%F, 40.5% by FMI, and 59.4% by VAT in the 70s. Notably, 22% of women with normal BMI (<23 kg/m²) had VAT > 100 cm², and 35.7% had A/G > 1.0, indicating central obesity. Conclusions: DXA-based indices provide a more accurate assessment of adiposity and associated cardiometabolic risks in aging women than BMI alone. Clinical screening strategies should consider incorporating regional fat distribution markers, particularly in midlife and postmenopausal populations, to better identify individuals at risk. Full article

Backgrounds/Objective: The impact of metabolic disturbances induced by an unbalanced diet on cognitive decline in mid-life is now widely observed, although the mechanisms are not well identified. Here we report that glutamatergic vasoactive pathways are a key feature of high-fat-diet (HFD)-induced neurogliovascular uncoupling in mice. Methods: C57Bl6/J mice are fed either with normal diet (ND) or high-fat diet (HFD) during 6 or 12 months and characterized for metabolic status. Cerebral vascular tree from pial to intraparenchymal arteries, is investigated with Halpern’s arteriography and with differential interference contrast infrared imaging of brain slices. Results: A 70% alteration in the myogenic tone of the basilar artery is observed as early as 6 months (M6) after the HFD. Infrared imaging revealed a 77% reduction in the glutamate-induced vasodilation of intraparenchymal arterioles appearing after 12 months (M12) of the HFD. The respective contributions of enzymes involved in glutamatergic pathways were altered as a function of HFD and time. The decrease in astrocytic COX I observed at M6 was followed by a loss of neuronal COX II and a compensatory action of NOS at M12. Conclusions: This HFD-induced neurogliovascular uncoupling pathway offers therapeutic targets to consider for improving cerebral vasoactive functions while preventing peripheral metabolic disturbances. Full article

Night shift work (NSW), has been associated with adverse health outcomes in women, including increased risks of metabolic disorders, cardiovascular diseases, and reproductive dysfunctions. However, the specific effects of NSW during the climacteric period remain underexplored. This narrative review aimed to examine original studies evaluating the health impacts of NSW on women in their climacteric, with a focus on menopausal timing, hormonal balance, and related symptoms. Relevant studies published in PubMed, Embase, and Scopus were reviewed in January 2025. Of 664 articles screened, 15 met the inclusion criteria. Results indicate that NSW may lead to circadian rhythm disruption, which in turn affects hormonal regulation, the timing of menopause, and the intensity of climacteric symptoms. Prolonged exposure to night shift work appears to increase the risk of metabolic and cardiovascular conditions, and certain cancers. These findings underscore the need to consider NSW as a potential modifiable risk factor for adverse health outcomes during midlife in women. They also highlight the importance of developing targeted occupational health policies and workplace interventions to mitigate these risks and promote healthier aging and quality of life. Full article

Hypertensive disorders of pregnancy are associated with a higher risk of later cardiovascular disease, but the mechanistic links are unknown. We recruited two groups of women, one during pregnancy and another at least two years after delivery, including both cases (with a hypertensive disorder of pregnancy) and controls (with a normotensive pregnancy). We measured metabolites using liquid chromatography–mass spectroscopy and applied machine learning to identify metabolomic signatures at three time points: antepartum, postpartum, and mid-life. The mean ages of the pregnancy cohort (58 cases, 46 controls) and the mid-life group (71 cases, 74 controls) were 33.8 and 40.8 years, respectively. The levels of 157 metabolites differed significantly between the cases and the controls antepartum, including 19 acylcarnitines, 12 gonadal steroids, 11 glycerophospholipids, nine fatty acids, six vitamin D metabolites, and four corticosteroids. The machine learning model developed using all antepartum metabolite levels discriminated well between the cases and the controls antepartum (c-index = 0.96), postpartum (c-index = 0.63), and in mid-life (c-index = 0.60). Levels of 10,20-dihydroxyeicosanoic acid best distinguished the cases from the controls both antepartum and postpartum. These data suggest that the pattern of differences in metabolites found antepartum continues to distinguish women who had a hypertensive disorder of pregnancy from women with a normotensive pregnancy for years after delivery. Full article

Japan’s shift to a super-aged society is reshaping household carbon footprint (HCF) in ways that vary by age, income, and region. Drawing on a two-tier national–prefectural framework, we quantify the influence of demographic shifts on HCF and evaluate inequalities, and project prefectural HCF to 2050 under fixed 2005 technology and consumption baselines. Nationally, emissions follow an inverted-U age curve, peaking at the 50–54 s (2.16 tCO₂) and dropping at both the younger and older ends. Carbon inequality—the gap between high- and low-income households—displays the opposite U shape, being the widest below 30 and above 85. Regional HCF patterns add a further layer: while the inverted U persists, its peak shifts to the 60–64 s in high-income prefectures such as Tokyo—where senior emissions rise by 44% by 2050—and to the 45–49 s in low-income prefectures such as Akita, where younger age groups cut emissions by 58%. Although spatial carbon inequality narrows through midlife, it widens again in old age as eldercare and home energy needs grow. These findings suggest that a uniform mitigation trajectory overlooks key cohorts and regions. To meet the 2050 net-zero target, Japan should integrate age-, income-, and region-specific interventions—for example, targeted carbon pricing, green finance for middle-aged consumers, and less-urban low-carbon eldercare—into its decarbonization roadmap. Full article

Retinoic acid (RA) exerts biological effects through RA receptors (RARs) to regulate transcription. RA also elicits rapid, RAR-independent (noncanonical) activities mediated by Cellular RA Binding Protein 1 (CRABP1) to modulate cytosolic signaling. CRABP1 functions by forming protein complexes, named CRABP1 signalosomes, to modulate signal propagation in a cell type-specific manner. This review summarizes multiple CRABP1 signalosomes and their physiological functions. CRABP1 knockout (CKO) mice develop multiple phenotypes progressively throughout the lifespan. These include altered brain function, obesity, and insulin resistance starting at young adult stages, increased vulnerability to heart failure and altered serum exosome profiles in midlife, and motor deterioration and thyroid dysfunction (hypothyroidism) in later life. The mouse Crabp1 gene is tightly regulated by multiple epigenetic mechanisms, whereas human CRABP1 gene dysregulation is associated with multiple human diseases in which age is an important factor. Further, CRABP1 expression in human and mouse thyroid glands gradually increases with aging. This underscores the clinical relevance of CRABP1 signalosomes in maintaining health and the functions of certain cells/organ systems, especially in the thyroid and during the aging process. The CRABP1 sequence is highly conserved, likely due to its functional constraint in forming various signalosomes; its tight regulation ensures proper expression of CRABP1 required for the forming of various signalosomes critical to the health and functions of multiple cell types/organ systems. Finally, CRABP1-specific (without activating RARs) signaling pathway-selective compounds have been designed. It may be an attractive therapeutic strategy to exploit these CRABP1-specific compounds to modulate selective signaling pathways in certain disease conditions, such as thyroid dysfunction, to maximize efficacy while minimizing retinoid toxicity. Full article

Menopause is associated with significant hormonal and reproductive changes in women. Evidence documents interindividual differences in the signs and symptoms associated with menopause, including cognitive decline. Hypothesized reasons for the cognitive decline include changes in hormone levels, especially estrogen, but study findings have been inconsistent. Hormone replacement therapies (HRTs) are often recommended to alleviate menopause-related symptoms in both peri- and postmenopausal women. However, the North American Menopause Society does not recommend the use of HRT for the management of cognitive complaints in perimenopausal women due to lack of evidence. Additionally, there are many women for which the use of HRT is contraindicated. As such, it would be helpful to have an alternative method for alleviating symptoms, including declines in cognition, during the menopause transition. Iron supplementation may be a promising candidate as it has been associated with improved cognitive performance in premenopausal women with iron deficiency and iron deficiency anemia. Because many women will experience heavy blood losses during perimenopause, they are at risk of becoming iron deficient and/or anemic. The use of iron supplementation in women with iron deficiency may serve to not only improve iron status but also to alleviate many of the signs and symptoms associated with perimenopause (lethargy, depressed affect, etc.), including cognitive decline. However, evidence to inform treatment protocols is lacking. Well-designed studies of iron supplementation in perimenopausal women are needed in order to understand the potential of such supplementation to alleviate the cognitive decline associated with perimenopause. Full article

Background: Individual nutrients are associated with cognitive performance, but there is less evidence on the relationship between overall dietary patterns and cognitive performance in midlife. Objective: To examine the relation between dietary patterns and cognitive performance in midlife adults within the Bogalusa Heart Study (BHS). Methods: Cross-sectional data from the 2013–2016 cycle of the Bogalusa Heart Study, a life-course prospective cohort study, were used to generate diet quality scores, including the Alternate Healthy Eating Index 2010 (AHEI), the Healthy Eating Index 2015 (HEI), and the Alternate Mediterranean Dietary Pattern (aMed), based on food frequency questionnaires. Cognitive scores assessing attention and processing, episodic memory, and executive function were generated through validated cognitive tests. Generalized linear and logistic regression models were fit with adjustment for potential confounders. Results: Of 1053 participants included in the analysis, the mean age was 48.18 (SD = 5.22) years; 38.94% were male; and 31.14% identified as Black. Higher diet quality scores were associated with a higher global cognitive score (P-trend = 0.01 for AHEI, 0.02 for HEI, and 0.04 for aMed) after adjusting for age, sex, race, employment, education, smoking status, total energy intake, physical activity, BMI, diabetes, and hypertension. In dichotomous outcome analyses, higher AHEI and aMed scores remained inversely associated with low cognition when adjusting for similar covariates (P-trend = 0.03 for AHEI, 0.03 for aMed), but the association was attenuated to non-significance for HEI. In joint effect analysis between employment and dietary patterns (P-interaction = 0.28 for AHEI, 0.01 for HEI, and 0.11 for aMed), unemployment with a lower quality diet was associated with lower cognitive performance (P-trend = 0.02 for AHEI, 0.02 for HEI, and 0.01 for aMed). Conclusions: A high-quality diet is associated with optimal cognitive performance among midlife adults, and unemployment status may influence this association. These findings suggest that dietary interventions during midlife may represent a public health strategy to preserve cognitive function and reduce future neurodegenerative disease burden, especially in disadvantaged populations. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating global health concern. Hypervirulent strains are on the rise, causing morbidities and mortalities worldwide. In tertiary care hospitals, critically ill patients, those undergoing invasive procedures, and pediatric and geriatric patients are at risk. It is not fully clear how strains adapt and specialize in humans and emerge despite the well-established commonality of the S. aureus genome from humans and animals. This study investigates the influence of age-, gender-, and source-specific profiles (clinical, intensive care unit (ICU vs. non-ICU)) on the evolution of hospital-associated (HA)-MRSA versus community-associated (CA)-MRSA lineages. A total of 253 non-duplicate S. aureus isolates were obtained from May 2023 to March 2025. The patients were stratified by age and gender in ICUs and non-ICUs. Standard microbiology methods and Clinical and Laboratory Standards Institute (CLSI) guidelines were used for identification and susceptibility testing, with cefoxitin and oxacillin disk diffusions and molecular diagnosis confirming MRSA. Mann–Whitney U and Chi-square tests assessed the demographic distributions, clinical specimen sources, and MRSA/methicillin-sensitive S. aureus (MSSA) prevalence. Of 253, 41.9% originated from ICUs (71% male; 29% female) and 58.1% from non-ICU wards (64% male; 36% female). In both settings, MRSA colonized the two extremes of age (10–29 and 70+) for males and females, with different mid-life peaks or declines by gender. However, the overall demographic distribution did not differ significantly between the ICU and non-ICU groups (p = 0.287). Respiratory specimens constituted 37% and had the highest MRSA rate (42%), followed by blood (24.5%) and wounds (10.3%). In contrast, MSSA dominated wounds (20.3%). Overall, 73.9% were resistant to cefoxitin and cefotaxime, whereas vancomycin, linezolid, daptomycin, and tigecycline remained highly effective. Younger non-ICU patients (10–29) had higher MSSA, whereas older ICU ones showed pronounced HA-MRSA profiles. By the virtue of methicillin resistance, all MRSA were classified as multidrug resistance. Thus, MRSA colonization of the two extremes of life mostly in ICU seniors and the dominance of invasive MSSA and CA-MRSA patterns in non-ICU youth imply early age- and gender-specific adaptations of the three lineages. MRSA colonizes both ICU and non-ICU populations at extremes of age and gender specifically. High β-lactam resistance underscores the importance of robust stewardship and age- and gender-specific targeting in screening. These findings also indicate host- and organ-specificity in the sequalae of MSSA, CA-MRSA, and HA-MRSA evolutionary dynamics, emphasizing the need for continued surveillance to mitigate MRSA transmission and optimize patient outcomes in tertiary care settings. Full article

Aging is associated with gradual mobility decline, often undetected until it affects daily life. This study investigates the potential of smartphone-based accelerometry to detect early age-related changes in gait and stair performance in middle-aged adults. Eighty-eight healthy participants were divided into four age groups: young (20–35 years), early middle-aged (45–54 years), late middle-aged (55–65 years), and older adults (65–80 years). They completed single-task, cognitive, and physical dual-task gait assessments and stair negotiation tests. While single-task walking did not reveal early changes, cognitive dual-task cost (DTC) of stride time variability deteriorated in late middle age. A strong indicator of early mobility changes was movement similarity, measured using dynamic time warping (DTW), which declined from early middle age for both cognitive DTC and stair negotiation. These findings highlight the potential of smartphone-based assessments, particularly movement similarity, to detect subtle mobility changes in midlife, allowing for targeted interventions to promote healthy aging. Full article

Background: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings. Methods: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through interviews. The participants’ coronary artery calcification (CAC) was measured using chest CT scans, and left-ventricular mass (LVM) was measured using M-mode echocardiography. The values of the individual social determinants of health (iSDH) index were determined based on individual-level measures and CAC using a supervised learning method—the Boosted Regression Tree (BRT) model. This index’s association with the LVM index (LVMI) was evaluated as an external validation using linear regression models adjusting for race, sex, BMI, smoking status, alcohol intake, and physical activity. Results: Each one-standard-deviation (SD) increase in the iSDH index was associated with an increase in LVMI ranging from 0.376 (95% CI −0.016, 0.767) at year 0 to 0.468 (95% CI 0.115, 0.821) at year 20. The association between the iSDH index and the LVMI was more pronounced as the participants aged. Also, the iSDH indices were more strongly associated with LVMI among Black participants (β = 0.969, 95% CI = 0.081, 1.858) than White participants (β = 0.202, 95% CI = −0.228, 0.633) at year 5. Conclusions: Higher iSDH indices in early adulthood were associated with increased LVMI values in midlife. The association between the iSDH index and CVD was stronger among Black adults than with White adults. Full article

Internet addiction is an emerging public health concern among adults, potentially affecting psychological well-being and sleep quality. Although a substantial body of research has focused on adolescents and younger adults, less is known about middle-aged and older adult populations. This study investigated the relationships between Internet addiction, sleep quality, and psychological well-being in 629 adults (aged 30–60 years) and examined the socio-demographic predictors of Internet addiction. Participants completed online questionnaires assessing Internet addiction, psychological well-being, and sleep quality (Pittsburgh Sleep Quality Index). The final sample had a mean age of 39.4 (SD = 7.8), with 53.4% female participants. Most were employed (77.9%), and nearly half held an undergraduate degree (49.1%). The mean Internet addiction score was 38.1 ± 13.6. Poor sleep quality was prevalent (67.2%), and Internet addiction was positively correlated with total PSQI scores (r = 0.593; p < 0.001). Higher psychological well-being was inversely associated with both Internet addiction (r = −0.417; p < 0.001) and poor sleep quality (r = −0.490; p < 0.001). Younger age, female gender, regular employment, and higher income predicted greater Internet addiction, whereas having an undergraduate degree was associated with lower scores. Taken together, the findings of this study emphasize the importance of addressing sleep quality and psychological well-being to mitigate excessive Internet use in mid-life and older populations, particularly among those at higher risk. Full article

Background: Few studies have examined whether sleep is related to dietary intake in aging adults. To address this gap, this study investigated (1) the associations between sleep duration and sleep quality with fruits and vegetables (FV), fiber, and fat intake in lower-income midlife and older adults and (2) sex differences in these relationships. Methods: Baseline data from 163 ethnically diverse, lower-income midlife and older adults in the NIH-funded Steps for Change trial were analyzed. Dietary intake was assessed using the Block Fruit/Vegetable/Fiber and Fat Intake Screeners, operationalized as weekly servings. Sleep duration (hours per night) and quality were self-reported via the Stanford WELL for Life Scale. Linear regression models assessed the association between sleep duration and FV, fiber, and fat intake, adjusting for potential confounding covariates with separate models for sleep quality. Sex differences were tested using interaction terms, with stratified models also used to explore differences. Results: The sample was 73.2% female, with a mean age of 70.5 (SD = 9.7) years (range: 41–99). The mean sleep duration was 6.8 (1.2) hours per night, with 79.2% reporting fairly or very good sleep quality. Mean weekly servings were 24 for FV, 7 for fiber, and 18 for fat. Sleep duration was positively associated with FV intake (β = 2.2; p = 0.02). The interaction between duration and sex was marginally significant (p = 0.08), with a positive association in males (β = 5.5; p = 0.02) but not in females (β = 0.9; p = 0.41). No significant associations were found between sleep duration and fiber or fat intake or between sleep quality and any dietary intake outcomes. Conclusions: This study found that longer sleep duration was associated with higher FV intake in males but not in females. These findings suggest the possibility of sex differences in the sleep–diet relationship among aging populations that merit further exploration in longitudinal studies. Full article