Association of past and current sleep duration with structural brain differences: A large population-based study from the UK Biobank.

OBJECTIVE: This study aimed to examine the association between past/current sleep duration and macro-/micro-structural brain outcomes and explore whether hypertension or social activity plays a role in such association. METHODS: Within the UK Biobank, 40 436 dementia-free participants (age 40-70 years) underwent a baseline assessment followed by a brain magnetic resonance imaging (MRI) scan 9 years later. Past (baseline) and current (MRI scans) sleep duration (hours/day) were recorded and classified as short (≤5), intermediate (6-8), and long (≥9). Brain structural volumes and diffusion markers were assessed by MRI scans. RESULTS: Compared with past intermediate sleep, past short sleep was related to smaller cortex volumes (standardized ß [95 % CI]: -0.04 [-0.07, -0.02]) and lower regional fractional anisotropy (FA) (-0.08 [-0.13, -0.03]), while past long sleep was related to smaller regional subcortical volumes (standardized ß: -0.04 to -0.07 for thalamus, accumbens, and hippocampus). Compared to current intermediate sleep, current short sleep was associated with smaller cortex volumes (-0.03 [-0.05, -0.01]), greater white matter hyperintensities (WMH) volumes (0.04 [0.01, 0.08]), and lower regional FA (-0.07 [-0.11, -0.02]). However, current long sleep was related to smaller total brain (-0.03 [-0.05, -0.02]), grey matter (-0.05 [-0.07, -0.03]), cortex (-0.05 [-0.07, -0.03]), regional subcortical volumes [standardized ß: -0.05 to -0.09 for putamen, thalamus, hippocampus, and accumbens]), greater WMH volumes (0.06 [0.03, 0.09]), as well as lower regional FA (-0.05 [-0.09, -0.02]). The association between current long sleep duration and poor brain health was stronger among people with hypertension or low frequency of social activity (all Pinteraction <0.05). CONCLUSIONS: Both past and current short/long sleep are associated with smaller brain volume and poorer white matter health in the brain, especially in individuals with hypertension and low frequency of social activity. Our findings highlight the need to maintain 6-8 h' sleep duration for healthy brain aging.

The association of the dietary inflammatory potential with risk of overall and site-specific cancers: A community-based longitudinal study in the UK Biobank.

OBJECTIVES: The association of the dietary inflammatory potential with cancer risk remains uncertain. We examined the relationship of the dietary inflammatory potential with risk of overall and site-specific cancers and explored its sex and age differences. DESIGN: A community-based longitudinal study. SETTING: Participants from the UK Biobank completed baseline surveys during 2006-2010 and were followed for up to 15 years to detect incident cancer. PARTICIPANTS: 170,899 cancer-free participants with dietary data available (mean age: 55.73 ± 7.95, 54.10% female). MEASUREMENTS: At baseline, dietary intake was assessed with a 24-h dietary record for up to 5 times. The inflammatory diet index (IDI) was calculated to assess the dietary inflammatory potential as a weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein (hsCRP) levels, and tertiled as low (indicating low-inflammatory diet), moderate, and high IDI (as reference). Overall and site-specific cancers were ascertained via linkage to routine hospital admission, cancer registry, and death certificate data. Data were analyzed using Cox regression and Laplace regression. RESULTS: During the follow-up (median 10.32 years, interquartile range: 9.95-11.14 years), 18,884 (11.05%) participants developed cancer. In multi-adjusted Cox regression, low IDI scores were associated with decreased risk of rectal cancer (hazard ratio [95% confidence interval, CI] 0.76 [0.61, 0.94]), thyroid cancer [0.45 (0.27, 0.74)], lung cancer [0.73 (0.61, 0.88)]. However, the association between IDI score and the risk of overall cancer was not significant. Laplace regression analysis showed that 10th percentile differences (95% CIs) of cancer onset time for participants with low IDI scores was prolonged by 1.29 (0.32, 2.27), 1.44 (0.58, 2.30), and 2.62 (0.98, 4.27) years for rectal cancer, thyroid cancer, and lung cancer, respectively, compared to those with high IDI scores. Stratified analysis revealed that low IDI scores were associated with a lower risk of rectal cancer (p interaction between IDI score and sex = 0.035) and lung cancer in males, but not in females, and with a reduced risk of thyroid cancer in females, but not in males. Moreover, low IDI scores were associated with a reduced risk of rectal cancer and lung cancer in the participants aged ≥60 years, but not in those <60 years, and with a reduced risk of thyroid cancer in those aged ≥60 years and <60 years. CONCLUSIONS: A low-inflammatory diet is associated with decreased risk and prolonged onset time of rectal cancer and lung cancer, especially among males and individuals aged ≥60 years, and thyroid cancer among females.

Association of cognitive reserve with the risk of dementia in the UK Biobank: role of polygenic factors.

BACKGROUND: It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions. AIMS: We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia. METHOD: Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression. RESULTS: In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61-0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35-1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17-0.31). CONCLUSIONS: High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.

Association of a low-inflammatory diet with survival among adults: The role of cardiometabolic diseases and lifestyle.

BACKGROUND & AIMS: Evidence on the association between dietary inflammation and longevity is limited. We aimed to examine the association of a low-inflammatory diet with mortality and longevity, and to explore whether cardiometabolic diseases (CMDs) and lifestyle factors may play a role in this association. METHODS: Within the UK Biobank, 188,443 participants aged 39-72 years (mean 56.07) were followed for up to 16 years to detect survival status from the death registry. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was calculated as weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein levels, and tertiled as low, moderate, and high IDI scores. Baseline lifestyle beyond diet was assessed by summing the number of healthy lifestyle factors (i.e., never smoking, regular physical activity, and normal BMI) and categorized as unfavorable (≤1) and favorable (≥2). Presence of CMDs was defined as having any one of type 2 diabetes, ischemic heart disease, atrial fibrillation, heart failure, and stroke. Data were analyzed using Cox regression, Laplace regression, and generalized structural equation modelling. RESULTS: During the follow-up (median 9.79 years, interquartile range: 9.68-10.57 years), 9178 (4.9%) participants died. In multi-adjusted Cox regression models, a low-inflammatory diet (i.e. low IDI score) was associated with lower risk of all-cause mortality [hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.78 to 0.86]. Laplace regression analysis showed that the multi-adjusted 10th percentile difference (10th PD, 95% CI) of death time was delayed by 0.80 (0.55, 1.06; P < 0.001) years for participants with a low IDI score compared to those with a high IDI score. In mediation analysis, 21.48% of the association between IDI and mortality was mediated by CMDs. In joint effect analysis, participants with a low IDI score and favorable lifestyle had a 42% lower risk of death (HR = 0.58, 95% CI: 0.54, 0.62) compared to those with a high IDI score and unfavorable lifestyle. There was a significant additive interaction between low IDI score and favorable lifestyle on decreased mortality. CONCLUSIONS: A low-inflammatory diet is associated with a lower risk of death and could prolong survival time. CMDs may partially mediate the IDI-mortality association. A favorable lifestyle beyond diet may augment the positive effect of a low-inflammatory diet on longevity.

Association of Kidney Function With Dementia and Structural Brain Differences: A Large Population-Based Cohort Study.

BACKGROUND: The association between kidney function and dementia risk and the mechanisms underlying this relationship remain unclear. METHODS: Within the UK Biobank, 191 970 dementia-free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and Cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2). Kidney function was categorized as normal (eGFR ≥ 90), mildly impaired (60 ≤ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self-reported medical history and medical records. During the follow-up, a subsample of 12 637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. RESULTS: Over the follow-up, 5 327 (2.8%) participants developed dementia. Compared to normal kidney function, there was an increased risk of dementia with moderate to severely impaired kidney function (hazard ratio = 1.53, 95% confidence interval [CI]: 1.32-1.76) but not mildly impaired kidney function. In Laplace regression, dementia onset among people with moderate to severely impaired kidney function occurred 1.53 (95% CI: 0.98-2.08) years earlier than those with normal kidney function. Moderate to severely impaired kidney function was related to significantly lower gray matter volume (ß = -0.11, 95% CI: -0.19 to -0.03), but not to other brain magnetic resonance imaging measures. CONCLUSIONS: Impaired kidney function is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the kidney function-dementia association.

Association of Motor Function With Cognitive Trajectories and Structural Brain Differences: A Community-Based Cohort Study.

BACKGROUND AND OBJECTIVES: The association of motor function with cognitive health remains controversial, and the mechanisms underlying this relationship are unclear. We aimed to examine the association between motor function and long-term cognitive trajectories and further explore the underlying mechanisms using brain MRI. METHODS: In the Rush Memory and Aging Project, a prospective cohort study, a total of 2,192 volunteers were recruited from the communities in northeastern Illinois and followed up for up to 22 years (from 1997 to 2020). Individuals with dementia, disability, missing data on motor function at baseline, and missing follow-up data on cognitive function were excluded. At baseline, global motor function was evaluated using the averaged z scores of 10 motor tests covering dexterity, gait, and hand strength; the composite score was tertiled as low, moderate, or high. Global and domain-specific cognitive functions-including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed-were measured annually through 19 cognitive tests. A subsample (n = 401) underwent brain MRI scans and regional brain volumes were measured. Data were analyzed using linear mixed-effects models and linear regression. RESULTS: Among the 1,618 participants (mean age 79.45 ± 7.32 years) included in this study, baseline global motor function score ranged from 0.36 to 1.82 (mean 1.03 ± 0.22). Over the follow-up (median 6.03 years, interquartile range 3.00-10.01 years), low global motor function and its subcomponents were related to significantly faster declines in global cognitive function (ß = -0.005, 95% CI -0.006 to -0.005) and each of the 5 cognitive domains. Of the 344 participants with available MRI data, low motor function was also associated with smaller total brain (ß = -25.848, 95% CI -44.902 to -6.795), total white matter (ß = -18.252, 95% CI -33.277 to -3.226), and cortical white matter (ß = -17.503, 95% CI -32.215 to -2.792) volumes, but a larger volume of white matter hyperintensities (ß = 0.257, 95% CI 0.118-0.397). DISCUSSION: Low motor function is associated with an accelerated decline in global and domain-specific cognitive functions. Both neurodegenerative and cerebrovascular pathologies might contribute to this association.

PECAM-1 drives ß-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

Assessing Healthy Aging Score and Its Association With All-Cause Mortality: Findings From the China Health and Retirement Longitudinal Study.

Background and Objectives: To construct a comprehensive healthy aging score (HAS) and explore its association with all-cause mortality and its potential interactions with other demographics on mortality. Research Design and Methods: This study included 5,409 participants aged ≥60 years from the China Health and Retirement Longitudinal Study. An HAS was constructed based on three dimensions of healthy aging including intrinsic capacity (IC), environmental support (ES), and chronic disease (CD), which were assessed at baseline, and categorized by tertiles (poor, moderate, and high). Participants were followed up biennially for all-cause mortality through the death registration or family interview from 2011 to 2018. Data were analyzed using Cox regression, Laplace regression, and receiver-operating characteristic analysis. Results: During 7 years of follow-up, 877 (16.21%) participants died. An HAS was constructed based on the cognition, mobility, and instrumental activity of daily living in the IC dimension; housing in the ES dimension; and hypertension, diabetes, chronic lung disease, stroke, and cancer in the CD dimension, which was associated with death. HAS seems a good predictor of all-cause mortality, with an area under the curve of 0.749. The hazard ratios and 95% confidence intervals for all-cause mortality related to moderate and poor HAS (vs high HAS) were 1.26 (1.01-1.56) and 2.38 (1.94-2.91), respectively. The median survival time was 2.46 years shorter in participants with poor HAS than those with high HAS. There were significant additive interactions of HAS with age, sex, and marital status on death. Discussion and Implications: Poor HAS may increase mortality and shorten survival, especially among older, male, and single adults.

Association of lifespan reproductive duration with depression in Swedish twins: The role of hormone replacement therapy.

OBJECTIVE: To examine the association between reproductive duration and postmenopausal depression (taking the use of hormone replacement therapy [HRT] into account). METHODS: In this population-based cohort study, 11 320 postmenopausal women (mean age 63.6 years) were followed for up to 18 years. Reproductive duration was categorized into three groups: short (≤34 years), average (35-39 years), and long (≥40 years). Depression was ascertained from the Sweden National Patient Registry. RESULTS: During the follow up, 593 (5.24%) women developed depression. In the multi-adjusted generalized estimating equation model, the odds ratios (ORs) of depression were 1.28 (95% confidence interval [CI] 1.05-1.55) and 1.25 (95% CI 1.01-1.55) for women with short and long reproductive durations, respectively, compared with those women with average reproductive duration. Women with a non-typical reproductive duration (≤34 or ≥40 years) who received HRT were at a higher risk of depression (OR 1.82, 95% CI 1.42-2.33). There was a significant additive interaction between non-typical reproductive duration and the use of HRT on depression (attributable proportion 0.26, 95% CI 0.03-0.50). CONCLUSION: Women with a short or long reproductive duration, especially those with a history of HRT use, have a higher risk of depression after menopause compared with those with an average reproductive duration.

Association of impaired kidney function with dementia and brain pathologies: A community-based cohort study.

INTRODUCTION: The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. METHODS: A total of 1354 dementia- and kidney disease-free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2-9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow-up, 453 participants died and underwent autopsies for neuropathological assessment. RESULTS: Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. DISCUSSION: Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. HIGHLIGHTS: Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

High lifelong cognitive reserve prolongs disability-free survival: The role of cognitive function.

INTRODUCTION: The association between cognitive reserve (CR) and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability-free survival and explored the extent to which cognitive function mediates this association. METHODS: Within the Rush Memory and Aging Project, 1633 dementia- and disability-free participants were followed annually for up to 22 years. Lifelong CR including education, early-/mid-/late-life cognitive activities, and late-life social activity was assessed and tertiled. RESULTS: CR score was dose-dependently associated with disability/death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93-0.99). Compared to low CR, the HR (95% CI) of disability/death was 0.82 (0.70-0.95) for high CR. The median disability-free survival time was prolonged by 0.99 (95% CI 0.28-1.71) years for participants with high CR. Cognitive function mediated 35.7% of the association between CR and disability-free survival. DISCUSSION: High lifelong CR was associated with prolonged disability-free survival. Cognitive function mediates about one-third of this association. Our findings underscore the importance of CR for healthy aging.

Association of life-course traumatic brain injury with dementia risk: A nationwide twin study.

INTRODUCTION: The impact of life-course traumatic brain injury (TBI) on dementia is unclear. METHODS: Within the Swedish Twin Registry (STR), 35,312 dementia-free twins were followed for up to 18 years. TBI history was identified via medical records. Data were analyzed using generalized estimating equation (GEE) and conditional logistic regression. RESULTS: In multi-adjusted GEE models, the odds ratio (OR, 95% confidence interval [CI]) of dementia was 1.27 (1.03-1.57) for TBI at any age, 1.55 (1.04-2.31) for TBI at 50 to 59 years, and 1.67 (1.12-2.49) for TBI at 60 to 69 years. Cardiometabolic diseases (CMDs) increased dementia risk associated with TBI at age 50 to 69 years. The ORs in GEE and conditional logistic regression did not differ significantly (P = .37). DISCUSSION: TBI, especially between ages 50 and 69 years, is associated with an increased risk of dementia, and this is exacerbated among people with CMDs. Genetic and early-life environmental factors may not account for the TBI-dementia association.

Pulmonary Function Trajectories Preceding Death Among Older Adults: A Long-Term Community-Based Cohort Study.

BACKGROUND: Poor pulmonary function (PF) has been linked to mortality, but the timing of PF changes before death remains unclear. We aimed to examine the association between PF and mortality and identify different PF trajectories precedes death. METHODS: Within the Rush Memory and Aging Project, 1 438 participants without chronic obstructive pulmonary disease were followed for up to 22 years. PF was assessed annually using a composite score (tertiled as low, medium, and high) based on forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory flow (PEF). Survival status was observed during the follow-up period. Data were analyzed using Cox regression, Laplace regression, and mixed-effect models. RESULTS: During the follow-up, 737 (51.25%) participants died. Compared to high PF, the hazard ratio (95% confidence interval [CI]) of mortality was 1.35 (1.05, 1.72)/1.63 (1.25, 2.12) for medium/low PF. The median survival time (95% CI) was shortened by 0.80 (0.01-1.61)/1.72 (0.43-3.01) years for participants with medium/low PF, compared to high PF. In multiadjusted trajectory analysis, the significant differences between decedents and survivors occurred at 7 years before death for composite PF (mean difference [95% CI]: 0.14 [0.02-0.25]), 6 years for FEV1 (0.21 [0.08-0.33]) and FVC (0.21 [0.08-0.34]), and 8 years for PEF (0.21 [0.06-0.37]), and became greater thereafter. CONCLUSION: Poor PF is associated with elevated mortality and shortens survival for nearly 2 years. An acceleration in PF decline tends to occur 7 years before death. Poor PF, together with its decline, might be a predictor of mortality among community-dwelling older adults.

Injurious falls before, during and after dementia diagnosis: a population-based study.

BACKGROUND: the timing of incident injurious falls at different stages of dementia diagnosis is unclear. OBJECTIVES: to identify when the occurrence of injurious falls begins to increase among individuals who are going to develop dementia, to explore the time point at which people living with dementia are at highest risk of injurious falls and to ascertain differences in fall-related factors pre- and post-dementia diagnosis. DESIGN: this study included 2,707 participants with incident dementia and 2,707 1:1 matched (i.e. same birth year and sex) controls without dementia. METHODS: dementia diagnosis and date of onset were identified from the National Patient Registry (NPR) and the Swedish Cause of Death Register following international criteria. Information on injurious falls and history of chronic disease was obtained from the NPR. Data were analysed using conditional Poisson regression and generalized estimating equation models. RESULTS: compared with controls, the incidence of injurious falls among participants with dementia started to increase beginning 4 years pre-diagnosis (incidence rate ratio [IRR] 1.70, 95% confidence interval [CI] 1.30-2.22), reaching a peak (IRR 3.73, 95% CI 3.16-4.41) in the year of dementia diagnosis. Heavy drinking, physically active and cardiometabolic diseases (CMDs) were associated with incident falls among those with dementia. CONCLUSION: people with dementia have a higher incidence of injurious falls beginning 4 years leading up to diagnosis and peaking during the year of diagnosis. Older age, female, heavy drinking, physically active and CMDs may predict injurious falls among people with dementia.

Association of depression with mortality in nationwide twins: The mediating role of dementia.

BACKGROUND: The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association. METHODS: From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45-64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively. RESULTS: In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46-2.00) for depression at any age, 1.72 (1.36-2.17) for early-life, 1.51 (1.19-1.90) for midlife, and 4.10 (2.02-8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09). CONCLUSIONS: Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.

Association between Dietary Fiber Intake and Mortality among Colorectal Cancer Survivors: Results from the Newfoundland Familial Colorectal Cancer Cohort Study and a Meta-Analysis of Prospective Studies.

We examined dietary fiber intake for its relevance to Colorectal cancer (CRC) survival in a cohort of CRC patients and a meta-analysis including results from four prospective cohort studies. We analyzed 504 CRC patients enrolled in the Newfoundland Familial Colorectal Cancer Study (NFCCS) who were newly diagnosed with CRC between 1999 and 2003. Follow-up for deaths was through April 2010. All participants completed a self-administered food frequency questionnaire to evaluate their dietary intakes one year before diagnosis. Multivariable Cox proportional hazard models were used to explore the associations of dietary fiber intake with all-cause mortality and CRC-specific mortality. In the meta-analysis, we identified prospective cohort studies published between January 1991 and December 2021 by searching PubMed, EMBASE, and Cochrane Library. Fixed-effects or random-effects models were used to combine the study-specific hazard ratio (HR) from our original analysis and three other cohorts. In the NFCCS, we found that CRC patients with the second quartile of dietary fiber intake had a 42% lower risk of all-cause mortality (HR: 0.58, 95% CI: 0.35-0.98) and 58% lower risk of CRC-specific mortality (HR: 0.42, 95% CI: 0.21-0.87) compared with those with the lowest quartile. In the meta-analysis, a similar inverse association between dietary fiber and total mortality was detected among CRC patients; each 10 g/day increase in dietary fiber intake was associated with a 16% decreased risk of total mortality. The dose-response meta-analysis showed a linear relationship between dietary fiber intake and all-cause mortality, with no sign of a plateau. For CRC-specific mortality, intriguingly, the benefit associated with increasing dietary fiber intake achieved its maximum at approximately 22 g/day, and no further reduction in CRC-specific mortality was observed beyond this intake level. Our results suggest that high dietary fiber intake may be associated with prolonged survival among CRC patients. Our findings add to the sparse literature on the role of dietary fiber in CRC survival.

Influence of cardiovascular risk burden on pulmonary function trajectory: role of physical and social activities.

The impact of cardiovascular risk burden on long-term trajectories of pulmonary function (PF) remains unclear. We examined the association of cardiovascular risk burden assessed by Framingham general cardiovascular risk score (FGCRS) with PF decline and explored whether cardiovascular diseases (CVD), physical and social activities play a role in the association. Within the Rush Memory and Aging Project, 1,442 participants (mean age:79.83) were followed up to 22 years. FGCRS at baseline was calculated and categorized into tertiles. Composite PF was measured annually based on peak expiratory flow, forced expiratory volume in one second, and forced vital capacity. We found that the highest FGCRS was associated with faster PF decline (ß: -0.013, 95% CI: -0.023 to -0.003) compared with the lowest FGCRS. There were significant interactions between higher FGCRS and low level of physical/social activity (ß: -0.014, 95% CI: -0.026 to -0.003)/(ß: -0.020, 95% CI:-0.031 to -0.009) or CVD(ß: -0.023, 95% CI:-0.034 to -0.011) compared to the low FGCRS with high level of physical/social activity or without CVD (P-interaction<0.05). Our results suggest that higher cardiovascular risk burden is associated with a faster PF decline, especially among people with CVD. High level of physical activity and social activity appears to mitigate this association.

Association of life-course reproductive duration with mortality: a population-based twin cohort study.

BACKGROUND: Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear. OBJECTIVE: This study aimed to examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such an association. STUDY DESIGN: A total of 11,669 women (mean age, 63.54 years) from the Swedish Twin Registry were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected on the basis of a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. The data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression. RESULTS: In the generalized estimating equation model, compared with those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68-0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24-1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio, 0.28; 95% confidence interval, 0.23-0.35) were at a lower risk of all-cause mortality than those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion, 0.584; 95% confidence interval, 0.016-1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=.67). CONCLUSION: A longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.

Association of Sleep Duration, Napping, and Sleep Patterns With Risk of Cardiovascular Diseases: A Nationwide Twin Study.

Background Although sleep disorders have been linked to cardiovascular diseases (CVDs), the association between sleep characteristics and CVDs remains inconclusive. We aimed to examine the association of nighttime sleep duration, daytime napping, and sleep patterns with CVDs and explore whether genetic and early-life environmental factors account for this association. Methods and Results In the Swedish Twin Registry, 12 268 CVD-free twin individuals (mean age=70.3 years) at baseline were followed up to 18 years to detect incident CVDs. Sleep duration, napping, and sleep patterns (assessed by sleep duration, chronotype, insomnia, snoring, and daytime sleepiness) were self-reported at baseline. CVDs were ascertained through the Swedish National Patient Registry and the Cause of Death Register. Data were analyzed using a Cox model. In the multiadjusted Cox model, compared with 7 to 9 hours/night, the hazard ratios (HRs) of CVDs were 1.14 (95% CI, 1.01-1.28) for <7 hours/night and 1.10 (95% CI, 1.00-1.21) for ≥10 hours/night, respectively. Compared with no napping, napping 1 to 30 minutes (HR, 1.11 [95% CI, 1.03-1.18]) and >30 minutes (HR, 1.23 [95% CI, 1.14-1.33]) were related to CVDs. Furthermore, a poor sleep pattern was associated with CVDs (HR, 1.22 [95% CI, 1.05-1.41]). The co-twin matched control analyses showed similar results as the unmatched analyses, and there was no significant interaction between sleep characteristics and zygosity (P values >0.05). Conclusions Short or long sleep (<7 or ≥10 hours/night), napping, and poor sleep patterns are associated with an increased CVD risk. Genetic and early-life environmental factors may not account for the sleep-CVD association.

Influence of Cardiovascular Risk Burden on Motor Function Among Older Adults: Mediating Role of Cardiovascular Diseases Accumulation and Cognitive Decline.

Purpose: This study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association. Methods: In Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis. Results: At baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9-9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (ß = -0.0038; 95% confidence interval [CI]: -0.0069 to -0.0008), dexterity (ß = -0.0056; 95% CI: -0.0093 to -0.0020), gait (ß = -0.0039; 95% CI: -0.0077 to -0.0001), and hand strength (ß = -0.0053; 95% CI: -0.0098 to -0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively. Conclusion: Higher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.