Social Determinants of Health, Genetic Susceptibility, and Risk of Dementia: A Prospective Cohort Study.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study

This study examined the relationship between sleep disorders and the risk of dementia in patients with newly diagnosed type 2 diabetes. This study used the Korean Health Screening Cohort data and included 39 135 subjects aged ≥40 years with new-onset type 2 diabetes between 2004 and 2007, with follow-up throughout 2013. Sleep disorders were measured by F51(sleep disorders not due to a substance or known physiological condition) or G47(sleep disorders) under International Classification of Diseases, Tenth Revision (ICD-10) codes as a primary diagnosis, and the adjusted hazard ratio (AHR) and 95% CI of all-cause dementia, Alzheimer disease, vascular dementia, and other dementia were estimated using multivariable Cox proportional hazards regression models. In the patients with type 2 diabetes with an age range between 42 and 84 years (M = 57.8, SD = 9.5), this study identified 2059 events of dementia during an average follow-up time of 5.7 years. In patients with type 2 diabetes, subjects with sleep disorders were associated with an increased risk of all-cause dementia (AHR, 1.46; 95% CI, 1.19-1.80), Alzheimer disease (AHR, 1.39; 95% CI, 1.02-1.88), and other dementia (AHR, 1.69; 95% CI, 1.23-2.31) compared to those without sleep disorders. Men (AHR, 1.93; 95% CI, 1.42-2.62) and older adults (AHR, 1.70; 95% CI, 1.35-2.15) with sleep disorders were associated with an increased risk of dementia than their counterparts without sleep disorders among patients with type 2 diabetes. These findings suggest that sleep disorders are significantly associated with an increased risk of dementia in patients with new-onset type 2 diabetes.

Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia. To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies. A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression. Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P = 0.03). Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66-0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45-0.85) for AD and 0.56 (95% CI: 0.36-0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61-0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39-0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68-0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.

Age at Onset of Heart Failure and Subsequent Risk of Dementia: A Longitudinal Cohort Study

BackgroundPrevious studies showed inconsistent results on the association of smoking with all-cause dementia and vascular dementia (VaD), and are limited by inclusion of a small number of studies and unexplained heterogeneity. Our review aimed to assess the risk of all-cause dementia, Alzheimer’s disease (AD) and VaD associated with smoking, and to identify potential effect modifiers.Methods and FindingsThe PubMed, Embase, Cochrane Library and Psychinfo databases were searched to identify studies that provided risk estimates on smoking and incidence of dementia. A random-effects model was used to yield pooled results. Thirty-seven studies were included. Compared with never smokers, current smokers showed an increased risk of all-cause dementia (risk ratio (RR) 1.30, 95% confidence interval (CI) 1.18–1.45), AD (RR 1.40, 95% CI 1.13–1.73) and VaD (RR 1.38, 95% CI 1.15–1.66). For all-cause dementia, the risk increased by 34% for every 20 cigarettes per day (RR 1.34, 95% CI 1.25–1.43). Former smokers did not show an increased risk of all-cause dementia (RR 1.01, 95% CI 0.96–1.06), AD (RR 1.04, 95% CI 0.96–1.13) and VaD (RR 0.97, 95% CI 0.83–1.13). Subgroup analyses indicated that (1) the significantly increased risk of AD from current smoking was seen only in apolipoprotein E ε4 noncarriers; (2) current smokers aged 65 to 75 years at baseline showed increased risk of all-cause dementia and AD compared to those aged over 75 or under 65 years; and (3) sex, race, study location and diagnostic criteria difference in risk of dementia was not found.ConclusionsSmokers show an increased risk of dementia, and smoking cessation decreases the risk to that of never smokers. The increased risk of AD from smoking is more pronounced in apolipoprotein E ε4 noncarriers. Survival bias and competing risk reduce the risk of dementia from smoking at extreme age.

Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia. We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer's disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence. In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31-1.77; severe: HR1.80, 95%CI 1.36-2.38), AD (mild: HR1.63, 95%CI 1.30-2.04; severe: HR2.18, 95%CI 1.45-3.27), VD (mild: HR1.68, 95%CI 1.19-2.37; severe: HR1.47, 95%CI 1.22-1.78), and NAVD (mild: HR1.47, 95%CI 1.22-1.78; severe: HR1.98, 95%CI 1.43-2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18-2.04) and NAVD (HR1.51, 95%CI 1.07-2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21-1.40; AD: HR1.30, 95%CI 1.21-1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14-2.12; AD: HR 2.55, 95%CI 1.19-3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16-1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01-2.99), AD (OR1.56, 95%CI 1.09-2.23), and NAVD (OR1.14, 1.02-1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13-2.33). Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.

Being physically active is protective against dementia. Yet, it is unknown when during the adult life course physical activity is most associated with dementia risk. To determine whether higher physical activity levels in early adult life, midlife, or late life are associated with lower risk of all-cause or Alzheimer disease (AD) dementia. This prospective cohort study used data from the Framingham Heart Study Offspring cohort. The offspring of participants in the original Framingham Heart Study cohort who were dementia free and had physical activity measured at baseline (early adult life [1979-1983], midlife [1987-1991], or late life [1998-2001]) were followed up for a mean (SD) of 37.2 (7.1), 25.9 (8.5), or 14.5 (6.6) years for the development of incident all-cause or AD dementia until December 31, 2023. Physical activity was self-reported using the physical activity index, a composite score weighted by hours spent sleeping and in sedentary, slight, moderate, or heavy activities. Physical activity was divided into quintiles (Q). All-cause and AD dementia were classified by expert consensus based on established diagnostic criteria. This study included 1526 early adult-life (mean [SD] age, 36.7 [4.7] years; 821 [53.8%] female), 1943 midlife (mean [SD] age, 54.0 [5.8] years; 1010 [52.0%] female), and 885 late-life (mean [SD] age, 71.0 [4.5] years; 473 [53.4%] female) participants. There were 567 cases of incident all-cause dementia during follow-up. Higher levels of midlife and late-life physical activity were associated with lower risk of all-cause dementia. Midlife and late-life physical activity levels in Q4 or Q5 were associated with lower risk of all-cause dementia compared with Q1 (midlife Q4: HR, 0.60; 95% CI, 0.41-0.89; midlife Q5: HR, 0.59; 95% CI, 0.40-0.88; late-life Q4: HR, 0.64; 95% CI, 0.42-1.00; late-life Q5: HR, 0.55; 95% CI, 0.35-0.87). There were no associations between early adult-life physical activity and dementia risk. Findings were similar for incident AD (369 cases). In this cohort study of adults in the Framingham Heart Study Offspring cohort, higher levels of midlife and late-life physical activity were associated with similar reductions in risk of all-cause and AD dementia. These findings may inform future efforts to delay or prevent dementia through timing interventions during the most relevant stages of the adult life course.

Association between exogenous hormone use and dementia: A prospective cohort study and synthetic analysis.

BackgroundSeveral epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D).Methods and findingsThis study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006–2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29–0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27–0.92) for AD (Ptrend = 0.06), and 0.41 (0.22–0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs.ConclusionsIn this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.

Dementia and hearing loss are both highly prevalent conditions among older adults. We aimed to examine the association between hearing aid use and risk of all-cause and cause-specific dementia among middle-aged and older-aged adults, and to explore the roles of mediators and moderators in their association. We used data from the UK Biobank, a population-based cohort study, which recruited adults aged 40-69 years between 2006 and 2010 across 22 centres in England, Scotland, and Wales. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs between self-reported hearing aid use status (hearing loss with or without hearing aids) at baseline and risk of dementia (all-cause dementia, Alzheimer's disease, vascular dementia, and non-Alzheimer's disease non-vascular dementia). Dementia diagnoses were ascertained using hospital records and death-register data. We also analysed the roles of mediators (self-reported social isolation, loneliness, and mood) and moderators (self-reported education and income, smoking, morbidity, and measured APOE allele status). After the exclusion of people who did not answer the question on hearing difficulties (n=25 081 [5·0%]) and those with dementia at baseline visit (n=283 [0·1%]), we included 437 704 people in the analyses. Compared with participants without hearing loss, people with hearing loss without hearing aids had an increased risk of all-cause dementia (HR 1·42 [95% CI 1·29-1·56]); we found no increased risk in people with hearing loss with hearing aids (1·04 [0·98-1·10]). The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes (Alzheimer's disease, vascular dementia, and non-Alzheimer's disease non-vascular dementia). The attributable risk proportion of dementia for hearing loss was estimated to be 29·6%. Of the total association between hearing aid use and all-cause dementia, 1·5% was mediated by reducing social isolation, 2·3% by reducing loneliness, and 7·1% by reducing depressed mood. In people with hearing loss, hearing aid use is associated with a risk of dementia of a similar level to that of people without hearing loss. With the postulation that up to 8% of dementia cases could be prevented with proper hearing loss management, our findings highlight the urgent need to take measures to address hearing loss to improve cognitive decline. National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation.

Previous findings on the link between metabolic syndrome (MetS) and the risk of all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), and cognitive decline are inconsistent. We systematically searched Embase, PubMed, Web of Science, the Cochrane Library, and Scopus up to June 2025 for prospective cohort studies conducted in community-based settings among adults aged 18years or older that reported risk estimates (e.g., relative risks, hazard ratios, or odds ratios) for the association between MetS and the risk of dementia or cognitive decline. Risk of bias for studies were assessed using ROBINS-I, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was applied to evaluate the certainty of evidence. Relative risks (RR) with 95%CI were computed using a random-effects inverse-variance method. Twenty-eight cohorts involving 6,753,197 participants were examined. MetS was significantly associated with a higher risk of all-cause dementia (RR = 1.11, 95%CI: 1.07-1.14; absolute risk difference: 2 more cases per 1000 persons), VD (RR = 1.33, 95%CI: 1.21-1.46; absolute risk difference: 7 more per 1000), and cognitive decline (RR = 1.24, 95%CI: 1.10-1.40; absolute risk difference: 5 more per 1000), all based on low-certainty evidence. No significant association was found between MetS and AD, with very low certainty. MetS components of hypertension, hyperglycemia, and low HDL-C were key risk factors, with a dose-response relationship observed between the number of MetS components and dementia risk. Subgroup analyses indicated MetS increased all-cause dementia risk in individuals under 70 (p-value for interaction: 0.048). MetS was positively associated with increased risk of all-cause-dementia, VD, and cognitive decline, but not AD. However, the effect sizes were modest and the certainty of evidence was low. Further prospective cohort studies are needed to confirm the associations.

Dementia and stroke are major global causes of disability, with modifiable lifestyle factors playing a significant role in their development. The updated LIfestyle for BRAin health (LIBRA2) score integrates 15 modifiable risk and protective factors to quantify lifestyle-based dementia risk, but its relationship with stroke and dementia subtypes remains unexplored. We investigated LIBRA2's association with stroke and dementia subtypes while also assessing potential interactions with genetic susceptibility. Prospective data were used from the French multicenter Three-City (3C) Study, with participants aged 65 years and older followed for up to 17 years. Weighted LIBRA2 scores at baseline were constructed based on the presence of 15 modifiable risk and protective factors, with higher scores representing higher lifestyle-based dementia risk. Cox proportional hazards models were used to study the association of LIBRA2 with incident dementia (and subtypes) and stroke, adjudicated by expert neurologist panels. Genetic susceptibility to dementia and stroke was assessed using APOE ε4 carriership and disease-specific genetic risk scores. Analyses included 4,731 participants for stroke (mean age 73.8 years, 60.1% female) and 4,737 participants for dementia (mean age 73.8 years, 59.9% female). One-point increases in LIBRA2 scores (theoretical range -6.1 to +25.7) were associated with increased dementia risk (hazard ratio [HR] 1.08; 1.06-1.11), with a stronger association for vascular and mixed dementia (HR 1.13; 1.08-1.18) compared with Alzheimer disease (AD) dementia (HR 1.06; 1.03-1.09). LIBRA2 was not significantly associated with incident stroke risk (HR 1.03; 0.99-1.07). No significant interaction was found between LIBRA2 and APOE ε4 carriership or disease-specific genetic risk scores in relation to dementia subtypes or stroke. LIBRA2 serves as a valuable tool for assessing lifestyle-related dementia risk and its subtypes but showed no association with stroke, highlighting the potential for a stroke-specific risk reduction model. These associations were independent of genetic disease susceptibility, reinforcing the universal benefits of lifestyle modifications on dementia risk reduction. The stronger association between LIBRA2 (and some individual components) and vascular or mixed dementia, compared with AD dementia, highlights the pivotal role of vascular mechanisms in the relationship between lifestyle and brain health.

osteoporosis significantly increases the risk of all-cause dementia, Alzheimer's disease dementia, and vascular dementia in Korean older women. Significance of the paper: early detection and treatment of osteoporosis may reduce dementia risk. Dementia and osteoporosis share common risk factors and are increasing in prevalence in the aging population. This study aimed to investigate the impact of osteoporosis on dementia and its subtypes in women using data from a population-based, health-screening cohort, with a follow-up period of more than 10years. This retrospective study included 66-year-old Korean women who participated in the "National Screening Program for Transitional Ages" from 2010 to 2011. Participants were categorized based on spine bone mineral density T-scores into three groups: normal (T-score ≥ - 1.0 standard deviation [SD]; 18.7%), osteopenia (- 2.5 SD < T-score < - 1.0 SD; 42.5%), and osteoporosis (T-score ≤ - 2.5 SD; 38.8%). Incident dementia cases were evaluated until 2021 using national healthcare claims databases. Fine-Gray subdistribution hazard models were used to assess the risks of all-cause dementia including Alzheimer's disease (AD) dementia and vascular dementia (VaD), accounting for death as a competing risk. The study included 131,872 dementia-free women aged 66years. Over an average follow-up of 10.4 ± 1.8years, 9399 individuals developed all-cause dementia (7.1%). Osteoporosis was associated with increased risks for all-cause dementia (adjusted subdistribution hazard ratio [asHR] 1.14; 95% confidence interval [CI] 1.08-1.21; p < 0.001), AD dementia (asHR 1.14; 95% CI 1.08-1.22; p < 0.001), and VaD (asHR 1.42; 95% CI 1.08-1.87; p = 0.013), compared to normal. Our findings highlight an association between osteoporosis and increased risks of developing all-cause dementia, AD dementia, and VaD. Further research is needed to explore the effects of early identification and treatment of osteoporosis in preventing dementia.

This study aimed to investigate the association between the Life's Essential 8 (LE8) score and incident all-cause dementia (including Alzheimer's disease [AD] and vascular dementia) in UK Biobank. A total of 259,718 participants were included in this prospective study. Smoking, non-HDL cholesterol, blood pressure, body mass index, HbA1c, physical activity, diet, and sleep were used to create the Life's Essential 8 (LE8) score. Associations between the score (both continuous and as quartiles) and outcomes were investigated using adjusted Cox proportional hazard models. The potential impact fractions of 2 scenarios and the rate advancement periods were also calculated. Over a median follow-up of 10.6 years, 4958 participants were diagnosed with any dementia. Higher LE8 scores were associated with lower risk of all-cause and vascular dementia in an exponential decay pattern. Compared with individuals in the healthiest quartile, those in the least healthy quartile had a higher risk of all-cause dementia (HR: 1.50 [95% CI: 1.37-1.65] and vascular dementia (HR: 1.86 [1.44-2.42]). A targeted intervention that increased the score by 10-points among individuals in the lowest quartile could have prevented 6.8% of all-cause dementia cases. Individuals in the least healthy LE8 quartile might develop all-cause dementia 2.45 years earlier than their counterparts. In conclusion, individuals with higher LE8 scores had lower risk of all-cause and vascular dementia. Because of nonlinear associations, interventions targeted at the least healthy individuals might produce greater population-level benefits.