ObjectiveTo investigate the associations of midlife diet quality with incident dementia and brain structure.DesignPopulation-based prospective study and cross-sectional study.SettingUK Biobank.ParticipantsIn total, 187,783 participants (mean age 56.8 years, 54.9% women) who completed the 24-hour recall dietary questionnaire were included in the prospective study. A subgroup of 25,380 participants (mean age 55.7 years, 52.9% women) with brain structure data were included in the cross-sectional study.Main exposure and outcome measuresCox proportional hazards models and linear regression models were used to examine the associations of seven diet quality scores, i.e., hPDI (Healthful Plant-based Diet index), MDS (Mediterranean Diet score), aMED (alternate Mediterranean diet), RFS (Recommended Food Score), DASH (Dietary Approaches to Stop Hypertension), MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay diet) and AHEI-2010 (the Alternative Healthy Eating Index-2010), with incident dementia and brain structure (estimated using magnetic resonance imaging), respectively.ResultsDuring a total follow-up of 1,969,993 person-years, 1,363 (0.73%) participants developed dementia. Higher diet quality scores (except for hPDI) were consistently associated with a lower incidence risk of dementia (all P for trend<0.001). For instance, for RFS, the hazard ratios of the intermediate tertile group and the highest tertile group relative to the lowest tertile group were 0.85 (95% confidence interval [95%CI]=0.75 to 0.97) and 0.70 (95%CI=0.61 to 0.81), respectively. Moreover, higher diet quality scores were significantly associated with larger regional brain volumes including volumes of grey matter (GM) in the parietal and temporal cortex and volumes of the hippocampus and thalamus. For instance, higher RFS was associated with larger volumes of GM in the postcentral gyrus (β=16.05±4.08, P<0.001) and the hippocampus (β=5.87±1.26, P<0.001). A series of sensitivity analyses confirmed the main results.ConclusionGreater adherence to MDS, aMED, RFS, DASH, MIND, and AHEI-2010 were individually associated with lower risk of incident dementia and larger brain volumes in specific regions. This study shows a comprehensive picture of the consistent associations of midlife diet quality with dementia risk and brain health, providing mechanistic insights into the role of healthy diet in the prevention of dementia.Summary boxWhat is already known on this topicPrevious prospective studies and meta-analyses suggested significant associations between a few diet quality scores (i.e., MDS, DASH, MIND, and AHEI-2010) and the risk of dementia in different populations; however, the results did not reach agreement.Nutrient intakes or very few diet quality scores have been demonstrated to be associated with brain volumes derived from MRI. There is limited research on the associations of various diet quality scores with the risk of dementia and brain structures in the same population.What this study addsGreater adherence to MDS, aMED, RFS, DASH, MIND, and AHEI-2010, but not hPDI was individually associated with lower risks of incident dementia.Greater adherence to MDS, aMED, DASH, and AHEI-2010, especially RFS, was individually associated with larger brain volumes in special regions (e.g., parietal and temporal cortex, and hippocampus).This study shows a comprehensive picture of the consistent associations of midlife diet quality with dementia risk and brain health, providing mechanistic insights into the role of healthy diets in the prevention of dementia.

IMPORTANCE Accelerated aging makes adults more vulnerable to chronic diseases and death.Whether childhood adversity is associated with accelerated aging processes, and to what extent lifestyle mediates the association, remain unknown. OBJECTIVE To examine the associations of childhood adversity with a phenotypic aging measure and the role of unhealthy lifestyle in mediating these associations.

BackgroundAccelerated aging makes adults more vulnerable to chronic diseases and death. This study evaluates the association of childhood traumas with a phenotypic aging measure that captures mortality and morbidity risk, and the role of unhealthy lifestyle in mediating these associations.MethodsWe assembled data from 110,596 members of the UK Biobank aged 40-69 years who participated in the baseline survey (2006-2010) and online mental health questionnaire (2016). A phenotypic aging measure—Phenotypic Age Acceleration (PhenoAgeAccel) was calculated, with the higher value indicating the acceleration of aging. Body mass index, smoking status, alcohol consumption, physical activity, and diet were combined to construct an unhealthy lifestyle score (range: 0-5). Childhood traumas including physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse were assessed. General linear regression and formal mediation analysis were performed.ResultsEach individual childhood trauma and cumulative childhood traumas were significantly associated with PhenoAgeAccel. For instance, compared with participants who did not experience childhood traumas, those who experienced four (β=0.292, standard error [SE]: 0.091) or five childhood traumas had higher PhenoAgeAccel (β=0.669, SE: 0.169) in fully adjusted models. The formal mediation analysis revealed that unhealthy lifestyle partially mediated the associations of childhood traumas with PhenoAgeAccel (26.1%-42.6%).ConclusionsIn a large sample from UKB, childhood traumas were positively associated with acceleration of aging; and more importantly, unhealthy lifestyle partially mediated these associations. These findings reveal a novel pathway from childhood traumas to late-life health through lifestyle and underscore the potential of more psychological strategies beyond lifestyle interventions to promote healthy aging.

Background Aging-related inflammation is associated with chronic diseases and mortality. This study aimed to: 1) develop composite inflammaging metrics (CIMs) in UK biobank (UKB), and validate them in UKB and National Health and Nutrition Examination Survey (NHANES); 2) estimate mortality and CVD risk predictions of CIMs; 3) compare CIMs with single inflammatory blood biomarkers and conventional inflammatory indexes; 4) examine associations between lifestyles and CIMs. Methods We utilized algorithms including multiple linear regression, principal component analysis (PCA), allostatic load (AL), and Klemera and Doubal method (KDM), to develop four CIMs from five inflammatory blood biomarkers, using data of 438,321 adults (40-70 years) from UK Biobank (UKB). We validated these CIMs in UKB and 10,667 adults (20-84 years) from NHANES IV. We performed a parametric proportional hazard model based on Gompertz distribution to estimate CVD and mortality risk predictions of CIMs. Areas under receiver operating characteristic curves (AUCs) were calculated to compare the predictive abilities of CIMs. Multiple linear regression models were used to access associations between lifestyles and CIMs. Results With adjustment for age and sex, four CIMs were significantly associated with higher risks of all-cause mortality and incident CVD in UKB, among which CIMKDM outperformed the others (all-cause mortality: hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.46, 1.50; incident CVD: HR = 1.34, 95% CI = 1.33, 1.36). CIMKDM had the best discriminative ability for predicting 10-year survival and incident CVD in UKB (all-cause mortality: AUC = 0.728; incident CVD: AUC = 0.712). CIMs were responsive to lifestyle variables. For example, in UKB, compared to never smokers, current smokers had a significant increment in CIMKDM (coefficient = 0.30 SD, P < 0.001). Similar results were well validated in NHANES IV. Conclusions We developed and validated four novel CIMs that were predictive of mortality and CVD risk. CIMKDM outperformed the others and had the potential to be used in aging related preventive and intervention programs. Intervention programs targeting lifestyles could slow inflammaging and further reduce disease burden.

Background Arthritis is a common chronic disease, leading to poor quality of life, which has received increasing attention. This study aimed to examine the associations of arthritis with functional disability and depressive symptom among the general US adults. Methods Participants were from the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 1999–2018. Arthritis was self-reported or graded by the Kellgren-Lawrence score after an objective X-ray examination. Functional disability included disability in activities of daily living (ADL disability), instrumental activities of daily living (IADL disability) and mobility disability. Depressive symptom was assessed using the Patient Health Questionnaire (PHQ). Multivariable logistic regression models were used to examine the associations. Results We included 22,566 older adults (≥ 60 years; 10,961 had self-reported arthritis) for functional disability analysis (2,377 older adults with data on X-ray examination; 1,012 had radiographic knee osteoarthritis) and 32,056 adults (≥ 20 years; 9,175 had self-reported arthritis) for depressive symptom analysis. After controlling for all covariates, self-reported arthritis was associated with ADL disability (odds ratios [OR]: 2.68; 95% confidence interval [CI]: 2.50–2.87), IADL disability (OR: 2.06; 95% CI: 1.94–2.20) and mobility disability (OR: 2.95; 95% CI: 2.78–3.14), and depressive symptom (OR: 2.18; 95% CI: 1.98–2.40). In participants with data on X-ray examination, radiographic knee osteoarthritis was only associated with mobility disability (OR: 1.44; 95% CI: 1.18–1.74). Conclusions Arthritis was associated with functional disability and depressive symptom in general US adults. Appropriate managements of physical and mental health are needed for those with arthritis, to improve their quality of life.

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With a well-validated aging measure – Phenotypic Age Acceleration (PhenoAgeAccel), this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9,972 adults (20-84 years) from US National Health and Nutrition Examination Surveys (NHANES). The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident cardiovascular disease, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (P values <0.001) in UKB, respectively. The mediation proportion of PhenoAgeAccel in associations of lifestyles with cancer mortality, and all-cause mortality were 25.7%, and 35.2% (P values <0.05) in NHANES, respectively. This study demonstrated that accelerated aging partially mediated the associations of lifestyles with adverse health outcomes in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late-life beyond lifestyle interventions.

Background: We aimed to systematically evaluate the associations of frailty, a simple health indicator, with risks of multiple adverse outcomes in late life among adults with prediabetes. Methods: We evaluated 38,950 adults aged 40-64 years with prediabetes from the baseline survey of the UK Biobank. Frailty was assessed using the frailty phenotype (FP, 0-5), and participants were grouped into non-frail (FP =0), pre-frail (1≤ FP ≤2), and frail (FP ≥3). Multiple health outcomes were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Results: At baseline, 49.1% and 5.9% of adults with prediabetes were identified as pre-frail and frail, respectively. Both pre-frailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <0.001). For instance, compared with their non-frail counterparts, frail participants with prediabetes had a significantly higher risk (P <0.001) of type 2 diabetes mellitus (T2DM) (hazard ratio [HR]: 1.73), diabetes-related microvascular disease (HR: 1.89), cardiovascular disease (HR: 1.66), chronic kidney disease (HR: 1.76), eye disease (HR: 1.31), dementia (HR: 2.03), depression (HR: 3.01), and all-cause mortality (HR: 1.81) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Conclusions: In UK adults with prediabetes, both pre-frailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into the routine care for middle-aged adults with prediabetes, to improve the allocation of healthcare resources and reduce diabetes-related burdens.