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.

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.

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.

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.

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.

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.

Poor pulmonary function is associated with mild cognitive impairment, its progression to dementia, and brain pathologies: A community-based cohort study.

INTRODUCTION: The relationship between pulmonary function (PF) and mild cognitive impairment (MCI), dementia, and brain pathologies remains unclear. METHODS: A total of 1312 dementia-free participants, including a cognitively intact group (n = 985) and an MCI group (n = 327), were followed for up to 21 years to detect incident MCI and dementia. PF was assessed at baseline with a composite score and tertiled. Over follow-up, 540 participants underwent autopsies for neuropathological assessment. RESULTS: Compared to the highest PF, the hazard ratios (95% confidence intervals [CIs]) of the lowest PF were 1.95 (1.43-2.66) for MCI in the cognitively intact group and 1.55 (1.03-2.33) for dementia in the MCI group. Low PF was further related to Alzheimer's disease pathology (odds ratio [OR] 1.32, 95% CI 1.19-1.47) and vascular pathology (OR 3.05, 95% CI 1.49-6.25). DISCUSSION: Low PF increases MCI risk and accelerates MCI progression to dementia. Both neurodegenerative and vascular mechanisms may underlie the PF-dementia association.

Pulmonary function is associated with cognitive decline and structural brain differences.

The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia-free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain-specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross-sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain-specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association.

A healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes: a prospective nested case-control study in a nationwide Swedish twin cohort.

AIMS/HYPOTHESIS: We aimed to examine the association between type 2 diabetes and major subtypes of heart disease, to assess the role of genetic and early-life familial environmental factors in this association and to explore whether and to what extent a healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes. METHODS: In this prospective nested case-control study based on the Swedish Twin Registry, 41,463 twin individuals who were aged ≥40 and heart disease-free were followed up for 16 years (from 1998 to 2014) to detect incident heart disease. Type 2 diabetes was ascertained from self-report, the National Patient Registry and glucose-lowering medication use. Heart disease diagnosis (including coronary heart disease, cardiac arrhythmias and heart failure) and onset age were identified from the National Patient Registry. Healthy lifestyle-related factors consisted of being a non-smoker, no/mild alcohol consumption, regular physical activity and being non-overweight. Participants were divided into three groups according to the number of lifestyle-related factors: (1) unfavourable (participants who had no or only one healthy lifestyle factor); (2) intermediate (any two or three); and (3) favourable (four). Generalised estimating equation models for unmatched case-control design and conditional logistic regression for co-twin control design were used in data analyses. RESULTS: Of all participants, 2304 (5.5%) had type 2 diabetes at baseline. During the observation period, 9262 (22.3%) had any incident heart disease. In unmatched case-control analyses and co-twin control analyses, the multi-adjusted OR and 95% CI of heart disease related to type 2 diabetes was 4.36 (3.95, 4.81) and 4.89 (3.88, 6.16), respectively. The difference in ORs from unmatched case-control analyses vs co-twin control analyses was statistically significant (OR 1.57; 95% CI 1.42, 1.73; p < 0.001). In stratified analyses by type 2 diabetes, compared with an unfavourable lifestyle, an intermediate lifestyle or a favourable lifestyle was associated with a significant 32% (OR 0.68; 95% CI 0.49, 0.93) or 56% (OR 0.44; 95% CI 0.30, 0.63) decrease in heart disease risk among patients with type 2 diabetes, respectively. There were significant additive and multiplicative interactions between lifestyle and type 2 diabetes on heart disease. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with more than fourfold increased risk of heart disease. The association still remains statistically significant, even after fully controlling for genetic and early-life familial environmental factors. However, greater adherence to a healthy lifestyle may significantly mitigate the risk of heart disease related to type 2 diabetes. Graphical abstract.

Gestational diabetes mellitus and risks of gynecologic cancers: Results from a nationwide Swedish twin study.

BACKGROUND: Type 2 diabetes has been associated with increased risk of gynecologic cancers, yet the effect of gestational diabetes mellitus (GDM) on gynecologic cancers is unclear. OBJECTIVES: To examine associations between GDM history and subsequent gynecologic cancers in parous women, and to explore whether gestational hypertension (GH) plays a role in the associations. STUDY DESIGN: The population-based cohort study included 15,941 individuals from the Swedish Twin Registry. The history of GDM and GH was ascertained based on self-reports. Incident cases of gynecologic cancers (including cancers of the cervix, uterus, ovaries and other female genitalia) were obtained from the National Patients Registry and the Swedish Cancer Registry. Generalized estimating equation models were applied to analyze associations between GDM and gynecologic cancers. Stratified analysis was used to explore whether associations between GDM and gynecologic cancers differed by GH. Additive and multiplicative interactions were calculated between GDM and GH. RESULTS: Of all participants, 350 (2.2%) had GDM, and 1762 (11.1%) had incident gynecologic cancers. No statistically significant associations were found between GDM and risks of any gynecologic cancers. However, GDM was associated with an increased risk of ovarian cancer (OR = 5.29, 95% CI: 1.63-17.19) in women with GH. Interactions between GDM and GH were observed on the additive scale (Attributable proportion due to interaction: 0.86, 95% CI 0.42-1.30, P < 0.001). CONCLUSIONS: The associations between GDM and risks of gynecologic cancers were not evident, but the effect of GDM on the risk of ovarian cancer was modified by GH. Further validation in larger cohorts is warranted.

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study.

INTRODUCTION: The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. METHODS: Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. RESULTS: The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). CONCLUSIONS: A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.

Association of life-course depression with the risk of dementia in late life: A nationwide twin study.

INTRODUCTION: Whether depression is a prodromal phase or risk factor for dementia is under debate. We aimed to unveil the nature of depression-dementia association by looking into the time window of depression occurrence. METHODS: Dementia-free twins (n = 41,727) from the Swedish Twin Registry were followed-up for 18 years. Data were analyzed using generalized estimating equation (GEE) for all individuals and conditional logistic regression for co-twin matched pairs. RESULTS: In the GEE model, multi-adjusted odds ratios (ORs; 95% confidence intervals [CIs]) of dementia were 1.46 (1.09-1.95) for mid-life, 2.16 (1.82-2.56) for late-life, 2.24 (1.49-3.36) for mid- to late-life, and 2.65 (1.17-5.98) for lifelong depression. The ORs in conditional logistic regression and in GEE did not differ significantly (P = 0.60). Education ≥8 years attenuated dementia risk associated with mid-life depression. DISCUSSION: Not only late-life depression, but also mid-life depression is associated with dementia. Genetic and early-life environmental factors could not account for this association. Education ≥8 years might buffer the impact of mid-life depression on dementia.

Osteoporosis and Osteopenia Among Patients With Type 2 Diabetes Aged ≥50: Role of Sex and Clinical Characteristics.

INTRODUCTION/BACKGROUND: Although some studies have explored the association of adiposity and life habits (such as smoking) with osteoporosis and osteopenia among type 2 diabetes mellitus (T2DM) patients, the association between diabetic clinical characteristics (especially hypoglycemic drug use) and osteoporosis/osteopenia remains unclear. This study aimed to investigate the relationship of clinical characteristics with osteoporosis and osteopenia among T2DM patients by sex. METHODS: A total of 1222 T2DM patients aged ≥50 were included in the present study. Information on demographic, anthropometric and clinical characteristics was collected from medical records. Bone mineral density was assessed by dual-energy X-ray absorptiometry densitometer. Multiple adjusted logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of osteoporosis and osteopenia related to clinical characteristics. RESULTS: Of all participants, the prevalence of osteoporosis and osteopenia was 9.2% and 41.3%, respectively, and they were higher in females (14.7% and 48.5%) than in males (2.8% and 33%). After adjustment for potential confounders, the results showed that overweight (OR = 0.59; 95% CI, 0.42-0.81) and obesity (OR = 0.35; 95% CI, 0.24-0.50) were related to decreased odds of osteoporosis and osteopenia in both male and female T2DM patients, poor glycemic control (OR = 1.63; 95% CI, 1.08-2.47) was associated with increased odds of osteoporosis and osteopenia in males, and metformin treatment (OR = 0.65; 95% CI, 0.43-0.99) was associated with decreased odds of osteoporosis and osteopenia in females. CONCLUSIONS: Better glycemic management and rational choice of antidiabetic medication might be promising to prevent osteoporosis in T2DM patients. Further longitudinal studies are warranted to explore the association between antidiabetic treatment and osteoporosis.

Association of lifespan cognitive reserve indicator with the risk of mild cognitive impairment and its progression to dementia.

INTRODUCTION: The association of lifespan cognitive reserve (CR) with mild cognitive impairment (MCI) remains controversial. We aimed to examine the association of lifespan CR indicator with the risk of MCI and its progression to dementia, taking brain pathologies into account. METHODS: In a community-based cohort study (mean age, 79 years) with annual follow-up (median, 5.16 years; maximum, 20 years), a cognitively intact group (n = 1182) and an MCI group (n = 420) were identified at baseline. During the follow-up, 611 participants died and underwent autopsies. CR indicator encompassing education, early life to late-life cognitive and social activities were obtained and tertiled. RESULTS: The multi-adjusted hazard ratio (HR) of MCI was 0.72 (95% confidence interval [CI] 0.58 to 0.90) in the cognitively intact group, and the HR of dementia was 0.66 (95% CI 0.45 to 0.97) in the MCI group for participants with the highest CR indicator (reference: the lowest CR indicator). Among MCI participants with brain pathologies, dementia incidence was about 50% lower in people with the highest CR indicator than the lowest CR indicator. DISCUSSION: High lifespan CR indicator reduces risk of MCI, and delays its progression to dementia.

Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case-control study in a nationwide Swedish twin cohort.

AIMS/HYPOTHESIS: We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association. METHODS: In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs. RESULTS: Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780). CONCLUSIONS/INTERPRETATION: Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.

Overweight in midlife and risk of cancer in late life: A nationwide Swedish twin study.

Our study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late-life cancer risk and explored the role of genetic and early-life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30-50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case-control data (controlled for the clustering of twins within a pair). A co-twin matched case-control analysis used conditional logistic regression to compare cancer-discordant twins. Of all participants, 3968 (26.9%) were overweight and 4253 (28.8%) had cancer. In multi-adjusted GEE models using normal-weight (BMI 18.5-24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00-1.84, p = 0.049), liver cancer (OR 2.00, 95% CI: 1.11-3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19-6.91) and corpus uteri cancer (OR 1.78, 95% CI: 1.14-2.78) but lower risk of nonmelanoma skin cancer (OR 0.77, 95% CI: 0.66-0.90). In conditional logistic regression analysis, these associations were attenuated becoming nonsignificance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late-life colon, liver and uterine cancer but reduced risk of late-life nonmelanoma skin cancer. Further investigations are warranted to explore the role of genetic and early-life environmental factors in these associations.

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study.

The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged ≥ 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association.

Age at menarche and prevention of hypertension through lifestyle in young Chinese adult women: result from project ELEFANT.

BACKGROUND: Early and late age at menarche are associated with risk of hypertension, but little is known whether modifiable lifestyle can reduce this risk. METHODS: Our study leverages 60,135 healthy young Chinese women from the Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) study. Menarche age and lifestyle factors were assessed by self-reported questionnaires and hypertension was diagnosed by physicians. We estimated the odds ratios (ORs) of hypertension associated with menarche age using multivariable logistic regression. We further investigated whether modifiable lifestyles (body mass index, BMI; psychological stress; passive smoking; and imbalanced diet) increased risk in joint analyses. RESULTS: The association between age at menarche and hypertension was U-shaped, with age ≤ 12 at menarche giving the highest OR (1.46, 95% confidence interval [CI], 1.27-1.69) and ≥ 16 the second highest (OR = 1.36, 95% CI = 1.15-1.62). Simultaneous analysis of lifestyle risk factors and age of menarche showed that having one or more modifiable risk factors increased the menarche age-hypertension association. The risk of hypertension among participants with menarche age ≤ 12 decreased from OR 13.21 (95% CI = 5.17-29.36) with four high-risk lifestyle factors to 12.36 (95% CI = 9.51-16.05) with three high-risk factors, 5.24 (95% CI = 4.11-6.69) with two, and 2.76 (95% CI = 2.09-3.60) with one, in comparison to individuals with no high-risk lifestyle factors and menarche age 14. CONCLUSIONS: Our results suggest that modification of lifestyle, including maintenance of normal weight and a balanced diet, are associated with substantially reduce the risk of hypertension in high-risk individuals. Early and late age at menarche are risk factors for the development of hypertension in Western populations, and there is limited evidence that this is also true of Chinese populations. Targeted prevention of hypertension in vulnerable populations would be highly beneficial in efforts to reduce the incidence of cardiovascular disease, but it is not currently known whether lifestyle intervention could reduce hypertension risk. In this study, we analysed the risk of hypertension by age at menarche and four modifiable lifestyle factors (BMI, diet, psychological stress, and smoking tobacco) in a cohort of 60,135 young adult Chinese women (mean age 29). We identified that early and late age at menarche are associated with increased risk of hypertension in young Chinese women. There was joint effects between age at menarche and lifestyles on hypertension only participants with age at menarche ≤12 and being overweight or obese. Modification of lifestyle, including maintenance of normal weight and a balanced diet, can substantially reduce the risk of hypertension in high-risk individuals. In conclusion, our study has revealed that early and late menarche age are associated with the development of hypertension in young Chinese women, and that this risk is modified by healthy lifestyle traits.

Relation of socioeconomic status to overweight and obesity: a large population-based study of Chinese adults.

BACKGROUND: China has been going through significant changes in social and economical aspects and with great socioeconomic disparity in different regions. However, data on the association between socioeconomic status (SES) and obesity are not available in Tianjin, China. AIM: This study aimed to investigate the association between SES and high adiposity among the adult population in Tianjin. SUBJECTS AND METHODS: A total of 7351 individuals aged 20-79 were included in this study. Socioeconomic information was collected through an interview following a structured questionnaire. Waist circumference, body weight and height were measured following standard procedures. Overweight and obesity were defined according to the criteria of the Working Group on Obesity in China. Data were analysed using multinomial logistic regression with adjustment for potential confounders. RESULTS: Stratified analysis showed that higher monthly income and education were related to decreased odds of abdominal overweight/obesity in women, while high education was associated with increased odds of general overweight/obesity in men. Retirement increased the odds of abdominal overweight and obesity and non-manual work was associated with low odds of abdominal obesity in women. CONCLUSIONS: SES was associated with general and abdominal overweight/obesity and sex may play a role in such an association.