INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear.

METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations.

RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654).

DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation.

INTRODUCTION: The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear.

METHODS: In the UK Biobank, 46,562 dementia-free participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age-stratified (middle age [< 60] versus older [≥ 60]) mixed-effects models and linear regression.

RESULTS: A higher number of CMDs was associated with significantly steeper global cognitive decline in older (β = –0.008; 95% confidence interval: −0.012, −0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age.

DISCUSSION: CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age.

Background: The impact of late-life weight changes on incident dementia is unclear. We aimed to investigate the associations of body mass index (BMI) and weight changes with dementia and to explore the role of APOE ɛ4 in these associations.

Methods: A total of 1 673 dementia-free participants aged ≥60 and older were followed for an initial 6 years to detect changes in BMI/weight and then for an additional 6 years to detect incident dementia. BMI change ([BMI_{first 6-year follow-up} - BMI_baseline]/BMI_baseline) was categorized as stable (≤5%), and moderate (5%-10%) or large (>10%) gain or loss. Weight change (weight_{first 6-year follow-up} - weight_baseline) was categorized as stable (≤2.5 kg), and moderate (2.5-7.5 kg) or large (>7.5 kg) gain or loss. Dementia was diagnosed following standard criteria. Data were analyzed using Cox regression models.

Results: Over the second 6-year follow-up period, 102 incident dementia cases were identified. Compared with stable BMI, the hazard ratios (95% CI) of dementia were 2.61 (1.09-5.54) and 2.93 (1.72-4.91) for BMI gain or loss >10%, respectively. The risk of dementia was higher among APOE ɛ4 carriers experiencing a large BMI gain (9.93 [3.49-24.6]) or loss (6.66 [2.83-14.4]) than APOE ɛ4 noncarriers with stable BMI. Similar results were observed for weight change and dementia associations.

Conclusions: BMI and weight changes showed U-shaped associations with dementia risk. Large bodyweight gain and loss alike are associated with an almost 3-fold higher risk of dementia, which may be amplified by APOE ɛ4.

Background: The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples.

Methods: Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged >= 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS.

Results: In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64-2.47) and 1.76 (95%CI: 1.44-2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged < 70 years (P-interaction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04-1.63). The interaction of smoking with age was also replicated.

Conclusions: Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged < 70 years.

Social isolation has been recommended as a strategy for reducing COVID-19 risk, but it may have unintended consequences for mental well-being. We explored the relationship between social isolation and symptoms of depression and anxiety in older adults during the first wave of the COVID-19 pandemic and assessed the role of cardiometabolic diseases (CMDs) in this association. Between May and September 2020, 1,190 older adults from the Swedish National Study on Aging and Care in Kungsholmen were surveyed about their behaviors and health consequences during the first wave of the COVID-19 pandemic. In total, 913 (76.7%) participants reported socially isolating at home to avoid infection during this period. Social isolation was associated with a greater likelihood of reduced mental well-being (i.e., feelings of depression or anxiety) (OR: 1.74, 95% CI: 1.15-2.65). In joint exposure analysis, there was a significant likelihood of reduced mental well-being only among people who were socially isolating and had CMDs (OR: 2.13, 95% CI: 1.22-3.71) (reference: not isolating, CMD-free). In conclusion, social isolation as a COVID-19 prevention strategy was related to reduced mental well-being in an urban sample of Swedish older adults, especially among individuals with CMDs.

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.

BACKGOUND: 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. 

Background: The association of pulmonary function (PF) with motor function and disability remains unclear. We investigate the association of PF with motor function trajectories and disability progression, and explore the role of social activity, cognitive function, and cardiovascular diseases (CVDs) in this relationship.

Methods: Within the Rush Memory and Aging Project, 1 403 disability-free participants (mean age: 79.28 years) were followed for up to 22 years. PF was measured with a composite score based on peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity at baseline. Global motor function including dexterity, gait, and hand strength was assessed annually using 10 motor tests. Disability was evaluated according to the basic activities of daily living. Social activity was defined as the frequency of common types of social interaction. Global cognitive function was assessed using a battery of 19 cognitive performance tests. CVDs (including stroke, congestive heart failure, and heart diseases) were ascertained at baseline. Linear mixed-effects models were used.

Results: Compared to high PF, low PF was related to faster decline in global motor function (β = −0.005, 95% confidence interval [CI]: −0.008 to −0.001) and all 3 specific motor abilities (p < .05), as well as faster progression of disability (β = 0.012, 95% CI: 0.009 to 0.014). There was a statistically significant interaction between PF and social activity/cognitive function on disability progression (β = 0.005, 95% CI: 0.001 to 0.009, p = .010/β = 0.004, 95% CI: 0.001 to 0.009, p = .025).

Conclusion: Poor PF accelerates motor function decline and the progression of disability. A high level of social activity and cognitive function appear to decelerate disability progression related to poor PF.

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.

Background: Diabetes has been related to disability and excess mortality. We estimated the extent to which diabetes shortens disability-free survival and identified modifiable factors that may prolong disability-free survival in older adults with diabetes.

Methods: Disability-free older adults (n = 2 216, mean age: 71 years, female: 61%) were followed for up to 15 years. Diabetes was ascertained through medical examinations, medication use, or glycated hemoglobin ≥6.5% (48 mmol/mol). Disability-free survival was defined as survival until the occurrence of disability. A favorable (vs unfavorable) lifestyle profile was defined as the presence of at least 1 of the following: healthy (vs unhealthy) behaviors, active (vs inactive) engagement in leisure activities, or moderate-to-rich (vs poor) social network. Data were analyzed using Cox regression and Laplace regression.

Results: During the follow-up, 1 345 (60.7%) participants developed disability or died. Diabetes, but not prediabetes, was related to the outcome (hazard ratio [HR] 1.29, 95% CI 1.06–1.57), and 2.15 (1.02–3.27) years shorter median disability-free survival. In joint exposure analysis, disability-free survival was shortened by 3.29 (1.21–5.36), 3.92 (2.08–5.76), and 1.66 (0.06–3.28) years for participants with diabetes plus unhealthy behaviors, inactive engagement in leisure activities, or poor social network. Among participants with diabetes, a favorable profile led to a nonsignificant HR of 1.19 (0.93–1.56) for disability/death and prolonged disability-free survival by 3.26 (2.33–4.18) years compared to those with an unfavorable profile.

Conclusions: A healthy and socially active lifestyle may attenuate the risk of diabetes on disability or death and prolong disability-free survival among people with diabetes.