Life course weight transitions from birth to childhood to midlife and risk of cardiovascular diseases and its subtypes.

BACKGROUND AND AIMS: Evidence on weight transitions across life stages and cardiovascular diseases (CVDs) is limited. We aimed to explore weight transition patterns from birth to childhood to midlife and risk of incident CVDs. METHODS: A total of 193,905 participants from the UK Biobank were included. Weight at birth, childhood, and midlife were collected at baseline (2006-2010). CVD outcomes were collected at year 2022. We constructed 27 transition patterns from birth to age 10 years to midlife. Cox proportional hazard models yielded hazard ratios (HRs) and 95% confidence intervals (CI) between weight transition patterns and CVDs. Mediation analyses were performed. Rate advancement periods (RAP) were also calculated. RESULTS: Several weight transition patterns were clearly linked to risk of CVDs, including "Low birth weight → high weight at age 10 years → obesity at midlife" (HR 2.64, 95% CI 2.24-3.11), "Low birth weight → low weight at age 10 years → obesity at midlife" (2.27, 1.93-2.66), "High birth weight → low weight at age 10 years → obesity at midlife" (2.29, 1.96-2.67), and "High birth weight → high weight at age 10 years → obesity at midlife" (2.14, 1.89-2.42), which showed even stronger association with HF. RAPs of these patterns were 8.3-10.6 years for CVD and 10.0-13.1 for HF. 50% of the association between birth weight and CVDs was mediated by weight at midlife. CONCLUSIONS: Our findings highlight the importance of weight management throughout the life course in reducing the risk of CVDs, especially maintaining a heathy weight at midlife.

Age at menopause and all-cause and cause-specific dementia: a prospective analysis of the UK Biobank cohort.

STUDY QUESTION: Are there associations between natural or surgical menopause and incident dementia by age at menopause? SUMMARY ANSWER: Compared to age at menopause of 46-50 years, earlier natural menopause (≤40 and 41-45 years) was related to higher risk of all-cause dementia, while a U-shape relationship was observed between age at surgical menopause and risk of dementia. WHAT IS KNOWN ALREADY: Menopause marks the end of female reproductive period. Age at menopause reflects the length of exposure to endogenous estrogen. Evidence on the association between age at natural, surgical menopause, and risk of dementia has been inconsistent. STUDY DESIGN, SIZE, DURATION: A population-based cohort study involving 160 080 women who participated in the UK Biobank study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no dementia at baseline, and had no missing data on key exposure variables and covariates were included. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs on the association of categorical menopause age with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). Restricted cubic splines were used to model the non-linear relationship between continuous age at natural, surgical menopause, and risk of dementia. In addition, we analyzed the interaction effect of ever-used menopausal hormone therapy (MHT) at baseline, income level, leisure activities, and age at menopause on risk of dementia. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with age at menopause of 46-50 years, women with earlier natural menopause younger than 40 years (1.36, 1.01-1.83) and 41-45 years (1.19, 1.03-1.39) had a higher risk of all-cause dementia, while late natural menopause >55 years was linked to lower risk of dementia (0.83, 0.71-0.98). Compared to natural menopause, surgical menopause was associated with 10% higher risk of dementia (1.10, 0.98-1.24). A U-shape relationship was observed between surgical menopause and risk of dementia. Women with surgical menopause before age 40 years (1.94, 1.38-2.73) and after age 55 years (1.65, 1.21-2.24) were both linked to increased risk of all-cause dementia. Women with early natural menopause without ever taking MHT at baseline had an increased risk of AD. Also, in each categorized age at the menopause level, higher income level or higher number of leisure activities was linked to a lowers risk of dementia. LIMITATIONS, REASONS FOR CAUTION: Menopausal age was based on women's self-report, which might cause recall bias. WIDER IMPLICATION OF THE FINDINGS: Women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures to delay the development of dementia. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Start-up Foundation for Scientific Research in Shandong University (202099000066), Science Fund Program for Excellent Young Scholars of Shandong Provence (Overseas) (2022HWYQ-030), and the National Natural Science Foundation of China (82273702). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Healthy lifestyle and all-cause and cause-specific dementia in individuals with type 2 diabetes and the roles of diabetes duration and insulin use in UK Biobank cohort.

AIMS: To examine the effect of a healthy lifestyle score derived from seven lifestyle factors recommended by the diabetes management guidelines on all-cause and cause-specific dementia in individuals with type 2 diabetes mellitus (T2DM), and how diabetes duration and insulin use status modify their association. MATERIALS AND METHODS: This study analysed data of 459 840 participants from the UK Biobank. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals for the association of an overall healthy lifestyle score with all-cause and cause-specific dementia of Alzheimer's disease, vascular dementia and non-Alzheimer non-vascular dementia. RESULTS: Using diabetes-free participants who scored 5-7 as the reference group, in diabetes-free participants, we observed higher healthy lifestyle score was related to lower risk of all-cause and cause-specific dementia. However, in people with T2DM, those scored 2-3, 4 and 5-7 all had around the two-time risk of all-cause dementia (HR: 2.20-2.36), while those scored 0-1 had over a three-time risk (HR: 3.14, 95% confidence interval 2.34-4.21). A dose-response trend was observed with vascular dementia (each 2-point increase: 0.75, 0.61-0.93) and no significant association with Alzheimer's disease (0.95, 0.77-1.16). The reduced risk of all-cause and cause-specific dementia with higher lifestyle score was observed in patients with a diabetes duration less than 10 years, or in patients with no insulin use. CONCLUSION: In people with T2DM, higher healthy lifestyle score was associated with lower risk of all-cause dementia. Diabetes duration and insulin use moderated the association between healthy lifestyle score and risk of dementia.

Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression.

BACKGROUND: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-ß. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of AKT/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line. CONCLUSION: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

Atomic Engineering of Clusterzyme for Relieving Acute Neuroinflammation through Lattice Expansion.

Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 µM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.

Catastrophic health expenditure among single empty-nest elderly with multimorbidity in rural Shandong, China: the effect of co-occurrence of frailty.

BACKGROUND: Previous studies have indicated that older adults with multimorbidity had higher risk of incurring catastrophic health expenditure (CHE). However, the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity remains unclear. This study aims to explore the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity, and whether this effect is moderated by economic status. METHODS: A cross-sectional household survey of the older adults in 2019 in Shandong province, China. A total of 606 single empty-nest elderly aged 60 years or older were included in this study. CHE was defined as the out-of-pocket payments for health care that equals or exceeds 40% of the household' s capacity to pay. Logistic regression models are employed to examine the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity. The interaction term is introduced to explore the economic status difference in this effect. RESULTS: The CHE incidence for single empty-nest elderly with multimorbidity alone is 64.2%, and the co-occurrence of frailty results in an increase by almost 1.3 times (84.0%) in CHE incidence among single empty-nest elderly with multimorbidity. The co-occurrence of frailty increases the risk of incurring CHE among the single empty-nest elderly with multimorbidity, with the odds of incurring CHE increased by 3.19 times (OR = 3.19; P = 0.005). Furthermore, the interaction analysis shows that the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity still exist in lower economic status groups (OR = 4.64; P = 0.027), but not in higher economic status (OR = 2.76; P = 0.062). CONCLUSIONS: This study demonstrates that there is a positive effect of co-occurrence of frailty on the CHE among the single empty-nest elderly with multimorbidity, and this effect varies by economic status. The health policy-makers should reorganize the healthcare system to make it pro-poor, so as to meet the multiple medical demand and reduce the potential economic burden and inequalities of older adults.

Association of smoking status and health-related quality of life: difference among young, middle-aged, and older adults in Shandong, China.

PURPOSE: Few studies explored the relationship between smoking status and health-related quality of life (HRQOL) among adults in China. This study aims to explore the relationship between smoking status and HRQOL among adults (18 +) and examine whether there is a difference in this relationship among young, middle-aged, and older adults in China. METHODS: A total of 23,021 respondents were included in this study. The HRQOL is measured by EQ-5D-3L. The smoking status is divided into never smokers, current smokers, and former smokers. Tobit regression and Logistic regression are employed to explore the association between smoking status and HRQOL. The interaction term is included to explore the difference among young, middle-aged, and older adults. RESULTS: This study finds smoking status is significantly associated with HRQOL. An interaction analysis shows that the association between smoking status and HRQOL is significantly different among young, middle-aged, and older adults (P < 0.05). The smoking status is only significantly associated with HRQOL in middle-aged and older adults, but not for young adults. Compared with never smokers, former smokers report significantly lower EQ-5D-3L utility value in middle-aged adults (coefficient = - 0.089; 95%CI - 0.128 to - 0.050), current smokers report significantly higher EQ-5D-3L utility value in older adults (coefficient = 0.041; 95%CI 0.005 to 0.076). CONCLUSIONS: This study demonstrates a significant association between smoking status and HRQOL among adults in China, and there is a difference in this relationship among young, middle-aged, and older adults. The government should take efforts to formulate a variety of measures to control tobacco use among adults.

Physical multimorbidity and lifetime suicidal ideation and plans among rural older adults: the mediating role of psychological distress.

BACKGROUND: Previous studies have revealed that single physical chronic condition was associated with suicidal ideation/plans, but few studies have examined the relationship between multimorbidity and suicidal ideation/plans, and no studies have explored the underlying potential mechanism on this relationship in China. This study aimed to explore association between physical multimorbidity and suicidal ideation as well as plans, and further examine the mediating role of psychological distress (PD) on this relationship. METHODS: This study was based on the data from a survey about the health service of rural elderly household in Shandong, China. A total of 3242 adults aged 60 years and older were included in this study. PD was measured by Kessler Psychological Distress Scale (K10). Ordinal and binary logistic regression analyses were employed to explore the association between physical multimorbidity, PD and suicide ideation/plans. Bootstrapping analysis was further used to examine the mediation effect of PD on the association of multimorbidity and suicidal ideations/plans. RESULTS: The prevalence of multimorbidity, lifetime suicidal ideation, and suicidal plan in rural older adults was 35.2, 10.6 and 2.2%, respectively. Older adults living in rural areas with two or more chronic physical conditions experienced significantly higher risk of suicidal ideation and suicidal plans. The association between multimorbidity and suicidal ideations/plans was partially mediated by PD, of which, the mediating effect of PD accounted for 31.7 and 25.5% of the total effect, respectively. CONCLUSION: This study demonstrated the associations between physical multimorbidity and suicidal ideation/plans, and the mediating role of PD on this relationship among Chinese rural elderly. Healthcare providers in rural community should provide regular surveillance for the mental health status among the rural elderly with multimorbidity, and carry out various effective intervention measures to improve the mental health status, so as to reduce the risk of suicide.

Body mass index and mild cognitive impairment among rural older adults in China: the moderating roles of gender and age.

BACKGROUND: Evidence concerning the association between body mass index (BMI) and cognitive function among older people is inconsistent. This study aimed to investigate gender and age as moderators in association between BMI and mild cognitive impairment (MCI) among rural older adults. METHODS: Data were derived from the 2019 Health Service for Rural Elderly Families Survey in Shandong, China. In total, 3242 people aged 60 years and above were included in the analysis. Multilevel mixed-effects logistic regression was used to examine the moderating roles of gender and age, then further to explore the relationship between BMI and MCI. RESULTS: There were 601 (18.5%) participants with MCI. Compared with normal BMI group, low BMI group had a higher risk of MCI among older people [adjusted odds ratio (aOR) = 2.08, 95% confidence interval (CI): 1.26-3.44], women (aOR = 2.06, 95% CI: 1.35-3.12), or the older elderly aged ≥75 years old (aOR = 3.20, 95% CI: 1.34-7.45). This effect remained statistically significant among older women (aOR = 3.38, 95% CI: 1.69-6.73). Among older men, elevated BMI group had a higher risk of MCI (aOR = 2.32, 95% CI: 1.17-4.61) than normal BMI group. CONCLUSIONS: Gender and age moderated the association between BMI and MCI among Chinese rural older adults. Older women with low BMI were more likely to have MCI, but older men with elevated BMI were more likely to have MCI. These findings suggest rural community managers strengthen the health management by grouping the weight of older people to prevent the risk of dementia.

Catalytically active gold clusters with atomic precision for noninvasive early intervention of neurotrauma.

BACKGROUND: Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency. RESULTS: Herein, we proposed the noninvasive delivery route to brain trauma by employing highly active gold clusters with enzyme-like activity to achieve the early intervention. The decomposition rate to H2O2 of the ultrasmall gold clusters is 10 times that of glassy carbon (GC) electrodes, indicating excellent catalytic activity. The gold clusters can relieve the oxidative stress and decrease the excessive O2·- and H2O2 both in vitro and in vivo. Besides, gold clusters can accelerate the wound healing of brain trauma and alleviate inflammation via inhibiting the activation of astrocytes and microglia through noninvasive adminstration. decrease the peroxide and superoxide of brain tissue. CONCLUSIONS: Present work shows noninvasive treatment is a promising route for early intervention of brain trauma.

Subjective burdens among informal caregivers of critically ill patients: a cross-sectional study in rural Shandong, China.

BACKGROUND: Informal caregivers are the main source of care for the critically ill, especially after discharge or during the terminal stages at home. However, the concern for informal caregivers is often overshadowed by critically ill patients. The purpose of this study is to determine the influencing factors of the subjective burden of informal caregivers and to seek solutions accordingly. METHODS: Between July and August 2019, a cross-sectional study was conducted in Shandong, China, focusing on family caregivers and critically ill patients. Subjective caregiver burden was measured by the Chinese version of Zarit Burden Interview (ZBI). The stress process model was used to identify conditions relevant to the caregiving burden and to assess their impact on family caregivers. RESULTS: 554 samples were selected for analysis. The average scores of Zarit Caregiver Burden Interview (ZBI) scores in this study was 30.37±19.04 (n=554). ZBI scores of older, less educated, and spouse caregivers were significantly lower (4.12; 95%CI, 0.42 to 7.81; P =0.029). Objective and subjective burdens increased proportionally. Secondary role stress factors included the higher out-of-pocket (OOP) costs of critical diseases and lower household income, both of which increased caregivers' subjective burdens (1.28; 95%CI, -0.06 to 2.63; p=0.062). Formal medical aid systems played a positive role in reducing subjective caregiving burdens (-7.31; 95%CI, -13.23 to -1.40; p=0.016). CONCLUSIONS: Health policies should address both the direct medical burdens and the intangible psychological burdens of critical diseases.

What Role Does Activity Engagement Play in the Association between Cognitive Frailty and Falls among Older Adults? Evidence from Rural Shandong, China.

INTRODUCTION: Previous studies have demonstrated the relationship between cognitive frailty and falls among older adults. Activity engagement (AE) is known to be related to falls in older adults but the subject has been limited to empirical study. This study aimed to explore the mediating role of AE between cognitive frailty and falls among older adults in rural Shandong, China. METHODS: A total of 3,242 rural seniors (age ≥60 years; 63.6% women) were included in this cross-sectional study. Regression and bootstrap analyses were performed to explore the mediating role of AE between cognitive frailty and falls. RESULTS: The prevalence of falls was 13.1% and the prevalence of cognitive frailty was 6.6% among the participants. AE mediated the association between cognitive frailty and falls (95% CI 0.077-0.223). However, the direct effect was no longer significant after being adjusted for AE (95% CI -0.037 to 0.684; p = 0.078). CONCLUSION: Cognitive frailty was found to be associated with falls among rural older adults, and AE mediated this association. More attention should be paid to promote AE among Chinese rural older adults with cognitive frailty.

The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling.

BACKGROUND: Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are well-known to regulate T cell responses. However, their direct influence on the differentiation of B cell subsets remains largely elusive. This study investigated the effects of EgPSC-ESPs on the differentiation of IL-10-producing B cells (B10), and explored the possible role of Toll-like receptor 2 (TLR-2) signaling in this process. RESULTS: In comparison to phosphate buffered saline (PBS), B cells exposed to the excretory-secretory products (ESPs) generated higher percentages of B10 cells, with higher expression of IL-10 mRNA, and larger amount of IL-10 production, which were in a dose dependent way. The mRNA and protein expression of TLR-2 in the ESPs-stimulated B cells were significantly higher than those in PBS, which was consistent to the results in B cells isolated from EgPSC infected mice. Moreover, TLR-2-/- B cells in response to ESPs stimulation expressed lower levels of IL-10 mRNA and produced undetectable IL-10 in comparison to those in normal B cells. In addition, Phosphatase and tensin homolog deleted on chromosome ten/AKT/Phosphatidylinositol-3 kinase (PTEN/AKT/PI3K) pathway was activated in ESPs-treated B cells, which was also dependent on TLR-2 signaling. Pam3CSK4, the agonist of TLR-2, could mock the effects of ESPs on the expression of PTEN, AKT and PI3K. CONCLUSION: Overall, this study revealed that TLR-2 signaling was required for B10 induction mediated by EgPSC-ESPs, which might be an immunomodulatory target against the parasite infection.

Ionomycin inhibits Jurkat T cell behaviors in the presence of phorbol-12,13-dibutyrate.

Ionomycin in conjunction with phorbol-12,13-dibutyrate (PDBu) is conventionally used as a stimulator to activate cells, especially original T cells. But we accidently found it had an entirely opposite action on malignant tumor cells derived from T cells. Thus, influence of ionomycin on human leukemia Jurkat T cell behaviors and its preliminary mechanistic process were explored in the presence of PDBu. Ionomycin could remarkably inhibit colony formation of the cells, and inhibitory rate of the cell proliferation was increased with ionomycin treatment in a dose- or time-related relationship, following the reduction of ERK1/2 and phosphorylated-ERK1/2 levels. However, a high dose of ionomycin might moderately repress mid-stage activation of the cells. It also blocked the cell entry at S-phase and G2/M-phase with the attenuation of transforming growth factor-ß (TGF-ß) level in the cells, and promoted the cell apoptosis following the augment of caspase-3 and cleaved caspase-3 in the cells. The dramatic elevation of [Ca2(+)]i and intracellular pH (pHi) was simultaneously followed by the above alteration of the cell behaviors. These results indicate that ionomycin may strongly inhibit human acute T lymphocyte leukemia progress in the presence of PDBu through the inhibition of ERK1/2 signaling, the activation of caspase-3 and the attenuation of TGF-ß mediated by the [Ca2(+)]i and pHi enhancement, providing a novel insight into function and potential application of both ionomycin and PDBu.

Reproductive factors and their association with physical and comprehensive frailty in middle-aged and older women: a large-scale population-based study.

STUDY QUESTION: Are women's reproductive factors associated with physical frailty and comprehensive frailty in middle-age and later life? SUMMARY ANSWER: Early menarche at <13 years, age at menopause <45 years, surgical menopause, experiencing miscarriage and a shorter reproductive period of <35 years were associated with increased odds of frailty, while having two or three children was related to decreased likelihood of frailty. WHAT IS KNOWN ALREADY: Evidence has shown that women are frailer than men in all age groups and across different populations, although women have longer lifespans. Female-specific reproductive factors may be related to risk of frailty in women. STUDY DESIGN SIZE DURATION: A population-based cross-sectional study involved 189 898 women from the UK Biobank. PARTICIPANTS/MATERIALS SETTING METHODS: Frailty phenotype and frailty index were used to assess physical frailty and comprehensive frailty (assessed using 38 health indicators for physical and mental wellbeing), respectively. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CI between reproductive factors and likelihood of physical frailty and comprehensive frailty. Restricted cubic spline models were used to test the non-linear associations between them. In addition, we examined the combined effect of categorized age at menopause and menopause hormone therapy (MHT) on frailty. MAIN RESULTS AND THE ROLE OF CHANCE: There was a J-shape relationship between age at menarche, reproductive period, and frailty; age at menarche <13 years and >16 years, and reproductive period <35 years or >40 years were all associated with increased odds of frailty. There was a negative linear relationship between menopausal age (either natural or surgical) and odds of frailty. Surgical menopause was associated with 30% higher odds of physical frailty (1.34, 1.27-1.43) and 30% higher odds of comprehensive frailty (1.30, 1.25-1.35). Having two or three children was linked to the lowest likelihood of physical frailty (0.48, 0.38-0.59) and comprehensive frailty (0.72, 0.64-0.81). Experiencing a miscarriage increased the odds of frailty. MHT use was linked to increased odds of physical frailty in women with normal age at natural menopause (after 45 years), while no elevated likelihood was observed in women with early natural menopause taking MHT. LIMITATIONS REASONS FOR CAUTION: The reproductive factors were self-reported and the data might be subject to recall bias. We lacked information on the types and initiation time of MHT, could not identify infertile women who later became pregnant, and the number of infertile women may be underestimated. Individuals participating in the UK Biobank are not representative of the general UK population, limiting the generalization of our findings. WIDER IMPLICATION OF THE FINDINGS: The reproductive factors experienced by women throughout their life course can potentially predict frailty in middle and old age. Identifying these reproductive factors as potential predictors of frailty can inform healthcare providers and policymakers about the importance of considering a woman's reproductive history when assessing their risk for frailty. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Key Research and Development Program of China (2022YFC2703800), National Natural Science Foundation of China (82273702), Science Fund Program for Excellent Young Scholars of Shandong Province (Overseas) (2022HWYQ-030), Taishan Scholars Project Special Fund (No. tsqnz20221103), and the Qilu Young Scholar (Tier-1) Program (202099000066). All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Sex-specific associations between diabetes and dementia: the role of age at onset of disease, insulin use and complications.

BACKGROUND: Whether the association of type 2 diabetes (T2DM) with dementia was differed by sex remains unclear, and the roles of age at onset of disease, insulin use and diabetes' complications in their association are unknown. METHODS: This study analyzed data of 447 931 participants from the UK Biobank. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between T2DM and incident dementia [all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD)]. The roles of age at onset of disease, insulin use and diabetes' complications in their association were also analyzed. RESULTS: Compared to people with no diabetes at all, people with T2DM had increased risk of all-cause dementia (HR 2.85, 95% CI 2.56-3.17). The HRs between T2DM and AD were higher in women than men, with an RHR (95%CI) of 1.56 (1.20, 2.02). There was a trend that people who experienced T2DM before age 55 had higher risk of VD than those who had T2DM after age 55. In addition, there was a trend that T2DM had higher effect on VD that occurred before age 75 years than events that occurred after age 75. Patients with T2DM using insulin had higher risk of all-cause dementia than those without insulin, with an RHR (95%CI) of 1.54 (1.00-2.37). People with complications had doubled risk of all-cause dementia, AD and VD. CONCLUSIONS: Adopting a sex-sensitive strategy to address the risk of dementia in patients with T2DM is instrumental for a precision medicine approach. Meanwhile, it is warranted to consider patients' age at onset of T2DM, insulin use status and complications conditions.

Number of Live Births, Age at the Time of Having a Child, Span of Births and Risk of Dementia: A Population-Based Cohort Study of 253,611 U.K. Women.

Objectives: The association between birth-related factors and dementia is unclear. We aimed to investigate their association and subsequent risk of dementia in a large-scale follow-up prospective study. Materials and Methods: This population-based cohort study used data from U.K. Biobank (2006-2010), and the median follow-up was 12.0 years. Multivariable-adjusted Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) between number of children, age of first live birth, age of last live birth, span of births, and dementia. Restricted cubic spline models were used to quantify dose-response relationships. Results: A total of 253,611 women with mean age (standard deviation) of 56.3 (8.0) years were included. Compared with women with no child, women who had three or more children and first birth at age before 25 years, had elevated risk of all-cause dementia (HR: 1.30, 95% CI: 1.10-1.54), Alzheimer's disease (AD; 1.21, 1.00-1.46), and vascular dementia (VD; 1.59, 1.19-2.13). Also, women with three or more children and the last birth at age before 30 years, had increased risk of all-cause dementia (1.33, 1.11-1.59), AD (1.27, 1.03-1.57), and VD (1.55, 1.12-2.13). Moreover, women who had three or more children in <7 years, had an increased risk of all-cause dementia (1.25, 1.04-1.49). Dose-response relationship showed a lowest risk of dementia at having two children, and having three or more children in 7-9 years. Conclusions: Number of children, age of births, and span of births were all related to risk of dementia. These findings may help developing fertility policies or dementia prevention programs.

Midlife Life's Simple 7, Psychosocial Health, and Physical Frailty, Hospital Frailty, and Comprehensive Frailty 10 Years Later.

This study aims to examine the associations between midlife Life's Simple 7 (LS7) status, psychosocial health (social isolation and loneliness), and late-life multidimensional frailty indicators, and to investigate their synergistic effect on frailty. We used cohort data from the UK Biobank. Frailty was assessed using physical frailty phenotype, hospital frailty risk score, and frailty index. Cox proportional-hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between the LS7 score, psychosocial health, and frailty. For the association of LS7 with physical and comprehensive frailty, 39,047 individuals were included. After a median follow-up of 9.0 years, 1329 (3.4%) people were identified with physical frailty, and 5699 (14.6%) with comprehensive frailty. For the association of LS7 with hospital frailty, 366,570 people were included. After a median follow-up of 12.0 years, 18,737 (5.1%) people were identified with hospital frailty. Compared to people with a poor LS7 score, those with an intermediate (physical frailty: 0.64, 0.54-0.77; hospital frailty: 0.60, 0.58-0.62; and comprehensive frailty: 0.77, 0.69-0.86) and optimal LS7 score (physical frailty: 0.31, 0.25-0.39; hospital frailty: 0.39, 0.37-0.41; and comprehensive frailty: 0.62, 0.55-0.69) were associated with a lower risk of frailty. Poor psychosocial health was associated with an increased risk of frailty. People who had a poor psychosocial status and poor LS7 score had the highest risk of frailty. A better LS7 score in midlife was associated with a reduced risk of physical, hospital, and comprehensive frailty. There was a synergistic effect of psychosocial status and LS7 on frailty.

Long-Term Food Variety and Dietary Patterns Are Associated with Frailty among Chinese Older Adults: A Cohort Study Based on CLHLS from 2014 to 2018.

(1) Objective: To examine the association between posterior-derived dietary patterns, food variety, and frailty measured by frailty index (FI) in Chinese elderly. (2) Method: A cohort study based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2014 to 2018 was conducted among older adults. The food variety was defined by the food variety score (FVS), which was calculated using the frequency of food categories consumption. Dietary patterns were obtained using factor analysis. A FI composed of 38 health deficits was used to measure subjects' frailty status. Logistic regression analyses were performed to explore the correlation between dietary factors and the incidence of frailty. (3) Results: Compared with low FVS, a high dietary diversity score at baseline was not associated with a reduced incidence of frailty after four years. Regarding long-term food variety, compared with the low variety maintained group, people with high variety maintained were associated with a lower risk of frailty (0.59, 95%CI 0.39-0.90). Adherence to the "egg-bean-pickle-sugar pattern" and "fruit-vegetable-meat-fish pattern" was associated with a lower risk of frailty. (4) Conclusion: Maintaining high food variety and adherence to two patterns, i.e., the egg-bean-pickle-sugar pattern and fruit-vegetable-meat-fish pattern, could reduce the incidence of frailty among Chinese older adults.

Sex Differences in Memory: Do Female Reproductive Factors Explain the Differences?

Background: The sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors. Methods: Data were obtained from the China Health and Retirement Longitudinal Study. Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used. Results: The relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors. Conclusions: Postmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.