Association between probable sarcopenia and dementia risk: a prospective cohort study with mediation analysis.

The role of alcohol consumption as a mediator in the risk between sarcopenia and dementia remains inadequately studied. There is currently limited research on whether the association between sarcopenia and the risk of Alzheimer's disease (AD) is influenced by genetic susceptibility. Our study incorporated a total of 483,637 baseline non-dementia participants, who were classified into groups of individuals with no sarcopenia and those with probable sarcopenia based on the definition. We employed Cox proportional hazards models to evaluate the association between probable sarcopenia and the risk of all cause dementia (ACD), AD, and vascular dementia (VD). We conducted mediation analysis to explore the role of alcohol consumption in the association between probable sarcopenia and the risk of ACD, AD, and VD. During the median follow-up period of 13.6 years, we documented 9000 new cases of ACD (including 4061 AD and 2025 VD). Fully adjusted multivariate model revealed a significant correlation between probable sarcopenia and elevated risk for ACD (HR = 1.54, 95% CI: 1.46-1.62, p < 0.001), AD (HR = 1.32, 95% CI: 1.21-1.43, p < 0.001), and VD (HR = 1.69, 95% CI: 1.52-1.89, p < 0.001). Mediation analysis elucidates that alcohol consumption explained 12.8%, 15.2%, and 11.1% of the associations of probable sarcopenia with the risk of ACD, AD, and VD, respectively. An interactive relationship prevails between probable sarcopenia and genetic factors (p for interaction <0.001), and regardless of the degree of genetic risk, probable sarcopenia correlates with an elevated AD risk. Our study reveals a significant association between probable sarcopenia and an increased risk of dementia, with alcohol consumption playing a mediating role in this association. There is an interaction between probable sarcopenia and genetic susceptibility related to the risk of AD.

Association between coffee and tea consumption and the risk of dementia in individuals with hypertension: a prospective cohort study.

Many studies have shown that drinking coffee and tea may be associated with the risk of hypertension and dementia. Limited research exists on their impact on dementia risk in hypertensive patients. This study aimed to determine the association between coffee and tea consumption and the risk of dementia development in hypertensive population by utilizing Cox proportional risk modeling with 453,913 participants from a UK biobank. Our findings reveal a J-shaped and U-shaped association between the risk of all-cause dementia and the consumption of coffee and tea respectively in hypertensive people. The hypertensive patients who drink 0.5-1 cup of coffee or 4-5 cups of tea per day have the lowest risk of dementia. A U-shaped relationship was observed between daily caffeine consumption and the risk of developing all-cause dementia and vascular dementia in the hypertensive population. Furthermore, the significant association between the amount of coffee and tea consumed and the risk of all-cause and vascular dementia were more likely to be found in hypertensive patients than in the non-hypertensive population.

Thyroid dysfunction and risk of different types of dementia: A systematic review and meta-analysis.

BACKGROUND: The impact of thyroid function on the risk of various types of dementia, including Alzheimer's disease (AD) and vascular dementia (VD), remains unclear. This meta-analysis investigates the association between thyroid dysfunction and the risk of these dementia types, aiming to inform strategies for dementia prevention. METHODS: A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library for studies published up to February 2023, focusing on the risk of thyroid dysfunction in dementia. We excluded duplicates, studies without full text, those with incomplete data, animal studies, case reports, and reviews. Data analysis was performed using STATA 15.1 software. RESULTS: Our analysis indicated that overt hyperthyroidism significantly increases the risk of all studied dementia types (OR = 1.18, 95% CI: 1.04-1.35). In contrast, overt hypothyroidism was associated with a decreased risk of AD (OR = 0.73, 95% CI: 0.55-0.98) and VD (OR = 0.71, 95% CI: 0.62-0.82). Subclinical hyperthyroidism also showed a significant association with an increased risk of any dementia (OR = 1.26, 95% CI: 1.09-1.46) and specifically VD (OR = 6.70; 95% CI: 1.38-32.58). CONCLUSION: This study suggests that overt hypothyroidism may reduce the risk of dementia, including AD and VD, whereas overt and subclinical hyperthyroidism are linked to an increased risk. These findings highlight the importance of monitoring thyroid function as a preventative measure against dementia.

Osteoarthritis, osteoarthritis treatment and risk of incident dementia: a prospective cohort study based on UK Biobank.

BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.

Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.

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.

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

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

Association between new-onset atrial fibrillation and dementia among individuals with type 2 diabetes.

AIM: To assess the association between new-onset atrial fibrillation and dementia among patients with type 2 diabetes, a group with a high prevalence of atrial fibrillation. MATERIALS AND METHODS: This cohort study included 22 989 patients with type 2 diabetes from the UK Biobank. New-onset atrial fibrillation was ascertained from hospital admission records. We used an algorithm officially released by the UK Biobank to identify all-cause dementia, Alzheimer's disease and vascular dementia. The algorithm was developed using multiple sources, including hospital admissions and the death registry. Time-varying Cox regression analyses were performed to investigate the association between new-onset atrial fibrillation and dementia. RESULTS: A total of 2843 participants developed atrial fibrillation, whereas the remaining 20 146 did not. During the median of 12.3 years of follow-up, 844 all-cause dementia, 342 Alzheimer's disease and 246 vascular dementia cases occurred. Compared with participants without atrial fibrillation, those with atrial fibrillation had higher risks of all-cause dementia (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.80-2.57), Alzheimer's disease (HR 1.44, 95% CI 1.06-1.96) and vascular dementia (HR 3.11, 95% CI 2.32-4.17). CONCLUSIONS: New-onset atrial fibrillation was associated with a substantially higher risk of all-cause dementia, Alzheimer's disease and vascular dementia in patients with type 2 diabetes. Our findings highlight the significance of atrial fibrillation management in mitigating the risk of dementia in this demographic.

Intrinsic Capacity, Polygenic Risk Score, APOE Genotype, and Risk of Dementia: A Prospective Cohort Study Based on the UK Biobank.

BACKGROUND AND OBJECTIVES: The World Health Organization recently released a novel metric for healthy aging: intrinsic capacity (IC). The relationship between IC and the incidence of dementia, and its subtypes, is unknown. We aimed to analyze the relationship between IC and the incidence of dementia and its subtypes. Moreover, we tested whether genetic susceptibility to dementia could be modified by IC. METHODS: This cohort study involved 366,406 participants from the UK Biobank between 2006 and 2010. We analyzed 7 factors that reflected functional status across 4 IC domains to compute a comprehensive IC deficit score. Cox models were used to elucidate the relationship between the IC deficit score and the incidence of dementia. RESULTS: Among the 366,406 participants, 5,207 cases of dementia were documented, encompassing 2,186 and 1,175 cases of Alzheimer disease (AD) and vascular dementia (VD), respectively. Compared with participants with an IC score of 0, individuals with an IC score of 4+ had a markedly elevated risk of dementia (hazard ratio [HR] 2.17, 95% CI 1.92-2.45). In the joint analysis, for participants with a high polygenic risk score (PRS) and an IC score of 4 or more, the HR of all-cause dementia was 8.11 (95% CI 6.28-10.47) compared with individuals with a low PRS and an IC score of 0. Similar results were seen in the AD and VD groups. DISCUSSION: In summary, IC is associated with a higher risk of dementia, particularly in those combined with genetically predisposed to dementia.

Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study.

BACKGROUND: Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. METHODS: We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer's disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. RESULTS: 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer's disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18-1.48]) but a reduced risk of Alzheimer's disease (0.92 [0.84-1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65-1.96]), vascular dementia (2.95 [2.53-3.45]) and Alzheimer's disease (1.46 [1.26-1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25-3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer's disease (0.83 [0.75-0.91]) and all-cause dementia (0.9 [0.84-0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1-1.39]) but not Alzheimer's disease (1.0 [0.91-1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer's disease were only present in those without MASLD (0.78 [0.67-0.91]). CONCLUSIONS: MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.

Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk.

The prevention of thromboembolism in atrial fibrillation (AF) is typically restricted to patients with specific risk factors and ignores outcomes such as vascular dementia. This population-based cohort study used electronic healthcare records from 5,199,994 primary care patients (UK; 2005-2020). A total of 290,525 (5.6%) had a diagnosis of AF and were aged 40-75 years, of which 36,340 had no history of stroke, a low perceived risk of stroke based on clinical risk factors and no oral anticoagulant prescription. Matching was performed for age, sex and region to 117,298 controls without AF. During 5 years median follow-up (831,005 person-years), incident stroke occurred in 3.8% with AF versus 1.5% control (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.91-2.21; P < 0.001), arterial thromboembolism 0.3% versus 0.1% (HR 2.39, 95% CI 1.83-3.11; P < 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38-1.50; P < 0.001). AF was associated with all-cause dementia (HR 1.17, 95% CI 1.04-1.32; P = 0.010), driven by vascular dementia (HR 1.68, 95% CI 1.33-2.12; P < 0.001) rather than Alzheimer's disease (HR 0.85, 95% CI 0.70-1.03; P = 0.09). Death and thromboembolic outcomes, including vascular dementia, are substantially increased in patients with AF despite a lack of conventional stroke risk factors.

Brain health index as a predictor of possible vascular dementia in the Mexican health and aging study 2012-2015.

To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.

Motoric Cognitive Risk Syndrome as a Predictor of Adverse Health Outcomes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD), and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aimed to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from ten electronic databases. The Newcastle-Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR = 2.02; 95% CI = 1.94-2.11), cognitive impairment (adjusted RR = 1.72; 95% CI = 1.49-1.99), falls (adjusted RR = 1.32; 95% CI = 1.17-1.50), mortality (adjusted RR = 1.66; 95% CI = 1.32-2.10), and hospitalization (adjusted RR = 1.46; 95% CI = 1.16-1.84); MCR had more prominent predictive efficacy for AD (adjusted RR = 2.23; 95% CI = 1.81-2.76) compared to VaD (adjusted RR = 3.78; 95% CI = 0.49-28.95), while excluding analyses from the study that utilized the timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (hazard ratios [HR] = 1.69; 95% CI = 1.08-2.02) and frailty (OR = 5.53; 95% CI = 1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR = 1.22; 95% CI = 1.11-1.34 vs. adjusted RR = 1.19; 95% CI = 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes, and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis and provide evidence to support future targeted interventions.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

Unveiling the link between physical activity levels and dementia risk: Insights from the UK Biobank study.

BACKGROUND: There is limited information on the mixture effect and weights of light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) on dementia risk. METHODS: A prospective cohort study was conducted based on the UK Biobank dataset. We included participants aged at least 45 years old without dementia at baseline between 2006-2010. The weighted quantile sum regression was used to explore the mixture effect and weights of three types of physical activity on dementia risk. RESULTS: This study includes 354,123 participants, with a mean baseline age of 58.0-year-old and 52.4 % of female participants. During a median follow-up time of 12.5 years, 5,136 cases of dementia were observed. The mixture effect of LPA, MPA, and VPA on dementia was statistically significant (ß: -0.0924, 95 % Confidence Interval (CI): (-0.1402, -0.0446), P < 0.001), with VPA (weight: 0.7922) contributing most to a lower dementia risk, followed by MPA (0.1939). For Alzheimer's disease, MPA contributed the most (0.8555); for vascular dementia, VPA contributed the most (0.6271). CONCLUSION: For Alzheimer's disease, MPA was identified as the most influential factor, while VPA stood out as the most impactful for vascular dementia.

Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea.

OBJECTIVE: We aimed to examine the potential association between migraine and vascular dementia (VaD) using a nationwide population database. BACKGROUND: Migraine and VaD showed similar structural and functional changes in pathophysiology process and shared common risk factors, However, whether migraine prevalence increases VaD incidence remains controversial. METHODS: This retrospective population-based cohort study used the medical records from the Korean National Health Insurance System database. Migraine (G43) was defined by using the Tenth Revision of the International Classification of Diseases code. More than two migraine diagnoses at least 3 months apart were defined as "chronic migraine". Cox proportional hazards model estimated hazard ratios (HRs) of VaD for group comparisons. RESULTS: We included 212,836 patients with migraine and 5,863,348 individuals without migraine. During 10 years of follow-up, 3,914 (1.8%) and 60,258 (1.0%) patients with and without migraine, respectively, were newly diagnosed with VaD. After adjustment, patients with migraine showed a 1.21-fold higher risk of VaD than those without migraine (HR = 1.21; 95% confidence interval (CI): 1.17-1.25). Patients with chronic migraine showed a higher cumulative incidence of VaD than those with episodic migraine. The adjusted HR for the VaD incidence with migraine was higher in: (1) patients aged <65 years; (2) women; (3) patients without hypertension, diabetes, or atrial fibrillation; and (4) non-smokers. CONCLUSION: Migraine is associated with an increased risk of VaD, particularly in chronic migraine patients. Incidence of VaD in the setting of migraine may have distinct pathophysiology from that of VaD with traditional cardiovascular risks.

Sex matters in the association between cardiovascular health and incident dementia: evidence from real world data.

BACKGROUND: Cardiovascular health has been associated with dementia onset, but little is known about the variation of such association by sex and age considering dementia subtypes. We assessed the role of sex and age in the association between cardiovascular risk and the onset of all-cause dementia, Alzheimer's disease, and vascular dementia in people aged 50-74 years. METHODS: This is a retrospective cohort study covering 922.973 Catalans who attended the primary care services of the Catalan Health Institute (Spain). Data were obtained from the System for the Development of Research in Primary Care (SIDIAP database). Exposure was the cardiovascular risk (CVR) at baseline categorized into four levels of Framingham-REGICOR score (FRS): low (FRS < 5%), low-intermediate (5% ≤ FRS < 7.5%), high-intermediate (7.5% ≤ FRS < 10%), high (FRS ≥ 10%), and one group with previous vascular disease. Cases of all-cause dementia and Alzheimer's disease were identified using validated algorithms, and cases of vascular dementia were identified by diagnostic codes. We fitted stratified Cox models using age parametrized as b-Spline. RESULTS: A total of 51,454 incident cases of all-cause dementia were recorded over a mean follow-up of 12.7 years. The hazard ratios in the low-intermediate and high FRS groups were 1.12 (95% confidence interval: 1.08-1.15) and 1.55 (1.50-1.60) for all-cause dementia; 1.07 (1.03-1.11) and 1.17 (1.11-1.24) for Alzheimer's disease; and 1.34 (1.21-1.50) and 1.90 (1.67-2.16) for vascular dementia. These associations were stronger in women and in midlife compared to later life in all dementia types. Women with a high Framingham-REGICOR score presented a similar risk of developing dementia - of any type - to women who had previous vascular disease, and at age 50-55, they showed three times higher risk of developing dementia risk compared to the lowest Framingham-REGICOR group. CONCLUSIONS: We found a dose‒response association between the Framingham-REGICOR score and the onset of all dementia types. Poor cardiovascular health in midlife increased the onset of all dementia types later in life, especially in women.

The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer's disease, and vascular dementia: a UK Biobank based prospective cohort study.

BACKGROUND: Prior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations. OBJECTIVES: We aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence. METHODS: With a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank. RESULTS: Although 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07-1.31) for AD; 1.24 (1.08-1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02-1.19) for AD; 1.15 (1.03-1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively. CONCLUSIONS: Although our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence.

Occupational and domestic exposure associations with cerebral small vessel disease and vascular dementia: A systematic review and meta-analysis.

INTRODUCTION: The prevalence of cerebral smallvessel disease (SVD) and vascular dementia according to workplace or domestic exposure to hazardous substances is unclear. METHODS: We included studies assessing occupational and domestic hazards/at-risk occupations and SVD features. We pooled prevalence estimates using random-effects models where possible, or presented a narrative synthesis. RESULTS: We included 85 studies (n = 47,743, mean age = 44·5 years). 52/85 reported poolable estimates. SVD prevalence in populations exposed to carbon monoxide was 81%(95% CI = 60-93%; n = 1373; results unchanged in meta-regression), carbon disulfide73% (95% CI = 54-87%; n = 131), 1,2-dichloroethane 88% (95% CI = 4-100%, n = 40), toluene 82% (95% CI = 3-100%, n = 64), high altitude 49% (95% CI = 38-60%; n = 164),and diving 24% (95% CI = 5-67%, n = 172). We narratively reviewed vascular dementia studies and contact sport, lead, military, pesticide, and solvent exposures as estimates were too few/varied to pool. DISCUSSION: SVD and vascular dementia may be associated with occupational/domestic exposure to hazardous substances. CRD42021297800.

Hypertensive disorders of pregnancy and the risk of maternal dementia: a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney disease. However, their association with subsequent maternal dementia or cognitive impairment is less well understood. This study aimed to review and synthesize the published literature on hypertensive disorders of pregnancy and the subsequent risk for maternal dementia or cognitive impairment. DATA SOURCES: PubMed, Web of Science, Pyschinfo, and CINAHL were searched from database inception until July 31, 2022, for observational studies of hypertensive disorders of pregnancy and maternal dementia or cognitive impairment. STUDY ELIGIBILITY CRITERIA: Selected studies included the following: a population of pregnant women, exposure to a hypertensive disorder of pregnancy of interest, and at least 1 primary outcome (dementia) or secondary outcome (cognitive impairment). Two reviewers were involved in study selection. METHODS: We followed the Meta-analyses of Observational Studies in Epidemiology guidelines throughout. Random-effects meta-analyses were used to calculate the overall pooled estimates. Bias was assessed using an adapted version of the validated Newcastle-Ottawa Quality Assessment tool. RESULTS: A total of 25 eligible studies were identified and included 2,501,673 women. Preeclampsia was associated with a significantly increased risk for vascular dementia (adjusted hazard ratio, 1.89; 95% confidence interval, 1.47-2.43), whereas no clear association was noted between preeclampsia and Alzheimer's disease (adjusted hazard ratio, 1.27; 95% confidence interval, 0.95-1.70), nor between preeclampsia and any (undifferentiated) dementia (adjusted hazard ratio, 1.18; 95% confidence interval, 0.95-1.47). However, in an analysis restricted to women aged 65 years and older, preeclampsia was associated with an increased risk for Alzheimer's disease (adjusted hazard ratio, 1.92; 95% confidence interval, 1.35-2.73) and any dementia (adjusted hazard ratio, 1.87; 95% confidence interval, 1.21-2.91). CONCLUSION: Women whose pregnancies were complicated by preeclampsia seem to be at a substantially increased future risk for vascular dementia. The longer-term risks among these women with regards to Alzheimer's disease and other forms of dementia are less clear.