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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.

Objectives To examine the association between low birth weight (LBW) and cardiometabolic diseases (CMDs, including heart disease, stroke and type 2 diabetes mellitus) in adulthood, and to explore whether genetic, early-life environmental and healthy lifestyle factors play a role in this association. Design A population-based twin study. Setting Twins from the Swedish Twin Registry who were born in 1958 or earlier participated in the Screening Across the Lifespan Twin (SALT) study for a full-scale screening during 1998-2002 and were followed up until 2014. Participants 19 779 twin individuals in Sweden with birthweight data available (mean age: 55.45 years). Primary and secondary outcome measures CMDs were assessed based on self-reported medical records, medication use and records from the National Patient Registry. A lifestyle index encompassing smoking status, alcohol consumption, exercise levels and Body Mass Index was derived from the SALT survey and categorised as unfavourable, intermediate or favourable. Data were analysed using generalised estimating equation (GEE) models and conditional logistic regression models. Results Of all participants, 3998 (20.2%) had LBW and 5335 (27.0%) had incident CMDs (mean age at onset: 63.64 +/- 13.26 years). In GEE models, the OR of any CMD was 1.39 (95% CI 1.27 to 1.52) for LBW. In conditional logistic regression models, the LBW-CMD association became non-significant (OR=1.21, 95% CI 0.94 to 1.56). The difference in ORs from the two models was statistically significant (p<0.001). In the joint effect analysis, the multiadjusted OR of CMDs was 3.47 (95% CI 2.72 to 4.43) for participants with LBW plus an unfavourable lifestyle and 1.25 (95% CI 0.96 to 1.62) for those with LBW plus a favourable lifestyle. Conclusion LBW is associated with an increased risk of adult CMDs, and genetic and early-life environmental factors may account for this association. However, a favourable lifestyle profile may modify this risk.

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.

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.

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 followup (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.

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 incr

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.

Importance Evidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown. Objective To examine the association of lifespan CR with dementia risk, taking brain pathologies into account. Design, setting, and participants This study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018. Exposures Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest). Main outcomes and measures Dementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression. Results Of the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease-related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the low