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.

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.

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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.

Background Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. Objective We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. Methods We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. Results At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) 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%. Robust results were generally observed in sensitivity analyses. Conclusions In UK Biobank participants with prediabetes, both prefrailty 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 routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden.