Risk Of Incident Dementia Research Articles

Association of tooth location, occlusal support and chewing ability with cognitive decline and incident dementia.

Emerging evidence suggests association of tooth loss with impaired cognition. However, the differential effects of anterior versus posterior tooth loss, occlusal support loss and chewing ability are not considered comprehensively. We conducted cross-sectional (N = 4036) and longitudinal analyses (N = 2787) on data from Health 2000 and 2011 Surveys for associations of posterior occlusal support loss, anterior versus posterior tooth loss, and chewing ability with baseline cognition and 11-year cognitive decline. Additionally, 15-year incident dementia risk was investigated (N = 4073). After considering relevant confounders and potential reverse causality bias, posterior occlusal support loss significantly increased dementia risk across all categories indicative of posterior occlusal support loss (hazard ratios [HRs] between 1.99 and 2.89). Bilateral inadequate posterior occlusal support was associated with 11-year decline in overall cognition (odds ratio [OR] = 1.48:1.00-2.19), and unilateral inadequate posterior occlusal support with total immediate (OR = 1.62:1.14-2.30) and delayed recall decline (OR = 1.45:1.03-2.05). Moreover, posterior tooth loss was associated with dementia (HR = 2.23:1.27-3.91) and chewing ability with total immediate decline (OR = 1.80:1.04-3.13). Posterior tooth and occlusal support loss significantly increases dementia risk. The impact of posterior occlusal support loss appears to be dose-dependent, and this effect is distinct from that of dentures. Dental healthcare services should be particularly attentive to the state of posterior dentition. Further studies exploring possible mechanisms are warranted.

Motoric Cognitive Risk Syndrome and the Risk of Incident Dementia: A Systematic Review and Meta-Analysis of Cohort Studies

Background: Epidemiologic studies have indicated an association of motoric cognitive risk syndrome (MCR), a pre-dementia stage characterized by the presence of cognitive complaints and a slow gait, with increased risk of incident dementia. Objectives: We aimed to clarify this association using meta-analysis. Methods: We systematically searched the PubMed, Embase, and Web of Science databases up to December 2022 for relevant studies that investigated the association between MCR and incident all-cause dementia and Alzheimer’s disease (AD). The random-effects model was used to determine a pooled-effect estimate of the association. Results: We identified seven articles that corresponded with nine cohort studies investigating the association between MCR and the risk of dementia. Pooled analysis showed that MCR was associated with a significantly increased risk of incident all-cause dementia (HR = 2.28; 95% CI: 1.90–2.73) and AD (HR = 2.05; 95% CI: 1.61–2.61). Sensitivity analysis showed that there was no evidence that individual studies influenced the pooled-effect estimate, verifying the robustness of the results. Conclusions: Our results confirm that MCR is an independent risk factor of incident all-cause dementia and AD. Future studies are needed to better understand the mechanisms underlying this association.

Prospective cohort study evaluating the association between influenza vaccination and neurodegenerative diseases

The effect of influenza vaccination (FluVac) on the risk of neurodegenerative diseases has not been well evaluated in prospective populations. We aimed to assess the association between FluVac and the risk of dementia and Parkinson’s disease (PD) in people aged 60 years or older through a prospective population-based cohort from the UK Biobank. A time-varying Cox regression model adjusted for baseline and repeatedly measured covariates was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between influenza vaccination and risk of dementia/PD. We took into account 70,938 participants in the cohort, including 38,328 participants who got vaccinated. During a median follow-up period of 12.2 years, 2087 incident dementia cases occurred, including 281 cases who received FluVac and 1806 cases who were not vaccinated. In addition, 742 incident PD cases occurred, among whom 131 cases received FluVac and 611 PD cases did not receive FluVac. FluVac was associated with reduced dementia risk with an HR of 0.83 (95% CI, 0.72–0.95) but was not associated with PD incidence (HR = 1.07; 95% CI, 0.87–1.32) after controlling baseline and repeatedly measured covariates. Further, among all dementia cases, there were 733 Alzheimer’s disease (AD) (94 vaccinated cases and 639 non-vaccinated cases), 307 vascular dementia (VD) (34 vaccinated cases and 273 non-vaccinated cases), and 1047 cases with other dementias (OD) (153 vaccinated cases and 894 non-vaccinated cases). The HRs for the associations between FluVac and AD, VD, and OD were 0.79 (95% CI, 0.63–1.00), 0.58 (95% CI, 0.39–0.86), and 0.94 (95% CI, 0.78–1.14) respectively. A dose-response relationship was found in the association between FluVac and dementia but not in the association with PD. A major limitation of the study is the low accuracy in the diagnosis of dementia subtypes, namely AD, VD, and OD. However, Results of sensitivity analyses were consistent with the primary analyses. In conclusion, influenza vaccination is significantly associated with a reduced risk of incident dementia but not PD in community-dwelling adults in the UK Biobank population.

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

Physical Exercise and Health, 6: Sedentary Time, Independent of Health-Related Physical Activity, as a Risk Factor for Dementia in Older Adults.

Sedentary behaviors are leisurely behaviors that occur during waking hours performed while lying down or seated; examples are relaxing, conversing, using a smartphone, watching television, traveling in private or public transport, and thinking or working at a desk. Sedentary behaviors are common in everyday life; the average person spends 9-10 h/d sedentary. Findings from meta-analyses show that higher levels of physical activity are associated with a reduced risk of dementia and that near-absence of moderate to vigorous physical activity is associated with an increased risk of dementia. Sedentariness is a clearly defined construct that is more than just low levels of physical activity. Sedentariness, therefore, merits independent study. In this context, a recent cohort study, conducted in elderly subjects (mean age, 67 years) who were followed for a mean of 6.7 years, found that sedentariness, independent of current levels of moderate to vigorous physical activity, was associated in a dose-dependent fashion with the risk of incident dementia; the finding held true when reverse causation was addressed through the exclusion of subjects who developed dementia within 4 years of follow-up. The adjusted 10-year risk of dementia rose from about 8% with sedentariness at 10 h/d to about 23% with sedentariness at 15 h/d; the difference is clinically meaningful. Limitations of studies in the field are that residual confounding cannot be excluded, and that no randomized controlled trials exist upon which guidance may be based. Nevertheless, it could be prudent to decrease sedentary behaviors if only because these have also been associated with other adverse physical and mental health outcomes. Additional subjects explained in this article include reverse causation and how it may be dealt with during research design and data analysis, individual participant data meta-analysis, and making sense of results that are reported in terms of "per 1,000 person-years."

Association between pre-dementia psychiatric diagnoses and all-cause dementia is independent from polygenic dementia risks in the UK Biobank

Psychiatric disorders have been associated with higher risk for future dementia. Understanding how pre-dementia psychiatric disorders (PDPD) relate to established dementia genetic risks has implications for dementia prevention. In this retrospective cohort study, we investigated the relationships between polygenic risk scores for Alzheimer's disease (AD PRS), PDPD, alcohol use disorder (AUD), and subsequent dementia in the UK Biobank (UKB) and tested whether the relationships are consistent with different causal models. Among 502,408 participants, 9352 had dementia. As expected, AD PRS was associated with greater risk for dementia (odds ratio (OR) 1.62, 95% confidence interval (CI), 1.59-1.65). A total of 94,237 participants had PDPD, of whom 2.6% (n=2519) developed subsequent dementia, compared to 1.7% (n=6833) of 407,871 participants without PDPD. Accordingly, PDPD were associated with 73% greater risk of incident dementia (OR 1.73, 1.65-1.83). Among dementia subtypes, the risk increase was 1.5-fold for AD (n=3365) (OR 1.46, 1.34-1.59) and 2-fold for vascular dementia (VaD, n=1823) (OR 2.08, 1.87-2.32). Our data indicated that PDPD were neither a dementia prodrome nor a mediator for AD PRS. Shared factors for both PDPD and dementia likely substantially account for the observed association, while a causal role of PDPD in dementia could not be excluded. AUD could be one of the shared causes for PDPD and dementia. Psychiatric diagnoses were associated with subsequent dementia in UKB participants, and the association is orthogonal to established dementia genetic risks. Investigating shared causes for psychiatric disorders and dementia would shed light on this dementia pathway. US NIH (K08AG054727).

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. After up to 5years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis

BackgroundDysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed...

Does Mild Functional Impairment Predict Dementia in Older Adults With Normal Cognition?

Functional impairment can be an early indicator of cognitive decline. However, its predictive utility in cognitively normal (CN) older adults remains unclear. This study aimed to determine whether mild functional impairment (MFI) in CN older adults could predict incident dementia over 6 years, in addition to assessing its association with cognitive performance. A longitudinal study with a 6-year follow-up. A cohort of 296 community-dwelling CN older adults. MFI was defined by cutoffs for impairment on an objective performance-based and/or subjective questionnaire-based functional assessment. Cox regression analysis was conducted to assess the relationship between MFI and risk of incident dementia and cognitive performances over 6 years. Linear regression analysis examined the association between MFI and baseline cognitive performance. There were no significant longitudinal associations between MFI and incident dementia or changes in cognitive performance over 6 years. Defining MFI using both performance-based and informant-reported assessments was predictive of dementia. Cross-sectional analyses demonstrated significant associations between MFI and poorer baseline global cognition and performance in attention, visuospatial ability, and executive functioning. CN older adults with MFI were not at an increased risk of developing dementia over 6 years. A definition of functional impairment requiring both performance-based and informant-based assessments may be useful in predicting dementia.

Abstract WMP13: The Modifying Effects of Psychosocial Health on the Association Between Cerebrovascular Health and Dementia Risk: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study

Introduction: Associations between magnetic resonance imaging (MRI) markers of vascular pathology and dementia risk in older adults have been established, but it remains less clear how lifestyle factors may modify this association. We hypothesized that a weaker association between MRI markers of vascular pathology and incident dementia will be present among older adults with strong as compared to poor psychosocial health in mid-life. Methods: Social support and social isolation were assessed among ARIC participants, aged 46 - 68, via self-reported questionnaires (1990 - 1992). Following categorization of both factors, participants were classified as having strong or poor mid-life psychosocial health. From 2011 - 2013, 1977 participants, aged 67 - 90, underwent 3T brain MRI quantifying white matter hyperintensity (WMH) volume, subcortical cerebral microbleeds (sCMB), infarcts, and white matter integrity through diffusion tensor imaging. Incident dementia cases were identified from time of imaging through December 31, 2019 (median follow-up: 6.4 years) with ongoing surveillance. Relative contributions of psychosocial health and MRI markers to incident dementia were evaluated with demographic and vascular risk factor-adjusted Cox-proportional hazard regression models. Results: Among 1612 dementia-free participants with measures of psychosocial health, MRI markers were associated with dementia risk in the hypothesized direction. Mid-life psychosocial health significantly modified the associations between sCMB and WMH, each, with incident dementia risk (Table 1; greater risk of dementia shown in individuals with poor psychosocial health). Conclusions: The elevated risk of dementia associated with sCMB and WMH is reduced in participants with strong psychosocial health in mid-life. Future studies evaluating social factors through the life course and the mechanisms by which they modify the relationship between pathology and dementia are needed.

Circulating sphingolipids in relation to cognitive decline and incident dementia: The Cardiovascular Health Study.

Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain. We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia. Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR]=1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR=1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia. Several sphingolipid species appear to be involved in cognitive decline and dementia risk. Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.

Impact of sleep duration and sleep disturbances on the incidence of dementia and Alzheimer's disease: A 10-year follow-up study

The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older adults (≥ 65) using data from the English Longitudinal Study of Ageing (ELSA) and further investigated the causal association in Mendelian randomization (MR) analysis. In total of 7,223 individuals, 5.7 % developed dementia (1.7 % Alzheimer's disease (AD)) within an average of 8 (± 2.9) years. Cox regression models and MR were employed. Long sleep duration (>8 h) was associated with 64 % increased risk of incident dementia and 2-fold high risk of AD compared to ideal sleep duration (7–8 h). This association was particularly evident in older-older adults (≥70 years) and those who consumed alcohol. Short sleep duration (<7 h) was associated with lower risk of incident dementia among older-older but higher risk among younger-older adults. Sleep disturbances and perceived sleep quality were not associated with dementia or AD. The MR study did not reveal causal associations between sleep duration and dementia. These findings suggest that self-reported short sleep in younger-older and long sleep in older-older adults and those with frequent alcohol consumption are associated with dementia. Early detection of these sleep patterns may help identify individuals at higher dementia risk.

Risk of Common Neurological Disorders in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders. We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model. In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy. Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance.

Association of the Sleep Regularity Index With Incident Dementia and Brain Volume.

Irregular sleep may increase the risk of cardiometabolic conditions, but its association with incident dementia is unclear. The aim of this study was to assess the association between sleep regularity, that is, the day-to-day consistency in sleep-wake patterns and the risk of incident dementia and related brain MRI endophenotypes. We used Cox proportional hazard models to investigate the relationships between sleep regularity and incident dementia in 88,094 UK Biobank participants. The sleep regularity index (SRI) was calculated as the probability of being in the same state (asleep/awake) at any 2 time points 24 hours apart, averaged over 7 days of accelerometry. The mean age of the sample was 62 years (SD = 8), 56% were women, and the median SRI was 60 (SD = 10). There were 480 cases of incident dementia over a median 7.2 years of follow-up. Following adjustments for demographic, clinical, and genetic confounders (APOE ε4), there was a nonlinear association between the SRI and dementia hazard (p [global test of spline term] < 0.001) with hazard ratios (HRs) following a U-shape pattern. HRs, relative to the median SRI, were 1.53 (95% CI 1.24-1.89) for participants with SRI at the 5th percentile (SRI = 41) and 1.16 (95% CI 0.89-1.50) for those with SRI at the 95th percentile (SRI = 71). In a subset with brain MRI (n = 15,263), gray matter and hippocampal volume tended to be lowest at the extremes of the SRI. Sleep regularity displayed a U-shaped association with risk of incident dementia. Irregular sleep may represent a novel dementia risk factor.

Association between Helicobacter pylori infection and incident risk of dementia: The AMI cohort.

Chronic infectious diseases are increasingly being considered as potential contributors to dementia risk. Among those infections, Helicobacter pylori, the main cause of chronic gastritis worldwide, has been suggested. As the prevalence of H. pylori infection has decreased, the main objective of this work was to reconsider the association between H. pylori infection and the risk of incident dementia, including Alzheimer's disease. Prospective cohort of 689 older (≥65 years) agricultural workers from Southwest France. Descriptive and comparative analyses were performed according to H. pylori status determined by serology at baseline. The risk of incident dementia according to H. pylori status over a 7-year follow-up was explored by survival analyses: Kaplan-Meier curve and Cox proportional hazards models. Two-hundred (29.0%) participants were H. pylori-positive at baseline. Compared to H. pylori-negative participants, they showed worse cognitive performances at baseline. Eighty-five incident dementia cases were diagnosed during the follow-up period. After adjustment for age, sex, education, apolipoprotein ε4, and several cardiovascular risk factors, H. pylori remained associated with an increased risk of dementia (HR 1.70, 95% CI, 1.05-2.74). The risk was stronger for Alzheimer's disease (HR 2.85, 95% CI, 1.58-5.12). Despite an observed decrease in H. pylori infection prevalence, this study provides evidence for the association between H. pylori infection and dementia. These results should encourage further research on the mechanisms underlying the contribution of infectious diseases to pathological brain aging, especially the influence of gut inflammation on the brain.

Feelings of tense and risk of incident dementia: A prospective study of 482,360 individuals

BackgroundThe relationship between feelings of tense, as a significant emotional distress, and dementia remains unclear. This study aimed to evaluate the association between feelings of tense and dementia. MethodsIn UK Biobank, feelings of tense were measured with a standard item. The primary outcome was all cause of dementia (ACD) and its subtypes (Alzheimer's disease (AD), vascular dementia (VD), and other dementia). Cox regression models analyzed the association between feelings of tense and dementia risk, while linear regression examined the correlation with neuroimaging outcomes. The potential association and joint effects of AD and tenseness were evaluated based on the established genetic risk score (GRS). ResultsDuring a median follow-up of 12.7 years among 482,360 participants, 7331 dementia cases were identified. Individuals with feelings of tense had a significantly increased risk of ACD (HR, 1.194; 95 % CI: 1.115–1.278), VD (HR, 1.164; 95 % CI: 1.007–1.346), and other dementia (HR, 1.181; 95 % CI: 1.081–1.289), but not AD in multi-adjusted models. This association persisted across various sensitivity analyses and exhibited some heterogeneity in subgroup analyses. Furthermore, feelings of tense are associated with total brain volume shrinkage, higher white matter hyperintensities, and decreased partial subcortical volume, particularly in the hippocampus. No interaction between tenseness and AD genetic susceptibility was observed (P for interaction =0.346). LimitationsOur study only considered feelings of tense measured at a one-time point. ConclusionsOur findings demonstrate a significant association between feeling of tense and elevated dementia risk, indicating that tenseness could serve as a modifiable psychological determinant for dementia.

Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong

Heart failure (HF) and dementia frequently co-exist with shared pathological mechanisms and risk factors. Our study aims to investigate the association between statin therapy and the risks of dementia and its subtypes among patients with HF. The Hong Kong Clinical Data Analysis and Reporting System database was interrogated to identify patients with incident HF diagnosis from 2004 to 2018, using ICD 9/ICD 10 codes. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N=54,004) and non-users (N=50,291). The primary outcomes were incident all-cause dementia, including subtypes of Alzheimer's disease, vascular dementia, and unspecified dementia. Cox proportional-hazard model with competing risk regression was performed to estimate the sub-distribution hazards ratio (SHR) with corresponding 95% confidence intervals (CI) of the risks of all-cause dementia and its subtypes that are associated with statin use. Of all eligible patients with HF (N=104,295), the mean age was 74.2±13.6 years old and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range [IQR]: 6.4-13.0), 10,031 (9.6%) patients were diagnosed with dementia, among which Alzheimer's disease (N=2250), vascular dementia (N=1831), and unspecified dementia (N=5950) were quantified separately. After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted SHR 0.80, 95% CI 0.76-0.84). Stratified by subtypes of dementia, statin use was associated with a 28% lower risk of Alzheimer's disease (SHR 0.72, 95% CI 0.63-0.82), 18% lower risk of vascular dementia (SHR 0.82, 95% CI 0.70-0.95), and a 20% lower risk of unspecified dementia (SHR 0.80, 95% CI 0.75-0.85). In patients with HF, statin use was associated with a significantly lower risk of all-cause dementia and its subtypes, including Alzheimer's disease, vascular dementia, and unspecified dementia. Both randomized trials and experimental studies to validate the potential neuroprotective effect of statin are warranted. No funding was provided for this study.

Late-Life Metabolic Dysfunction-Associated Steatotic Liver Disease and its Association With Physical Disability and Dementia.

The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, including among older adults. The number of older adults is also rising with concomitantly increasing rates of age-related physical and cognitive dysfunction. However, data on whether MASLD affects physical and cognitive function in older adults is limited. As such, we aimed to identify whether prevalent MASLD influences the risk of incident physical disability or dementia in initially healthy older adults. A post-hoc analysis of participants from the ASPREE-XT cohort study, which recruited community-dwelling older adults without a history of cardiovascular disease, dementia, or independence-limiting functional impairment. The Fatty Liver Index (to identify MASLD) was calculated in those with complete data. Cox proportional-hazards models were used to investigate the outcomes of dementia and persistent physical disability in participants with MASLD vs those without. Of the 9097 individuals included (mean age 75.1 ± 4.2 years; 45.0% men), 341 (3.7%) developed persistent physical disability and 370 (4.1%) developed dementia over a median follow-up of 6.4 years (IQR 5.3-7.5 years). When adjusting for known contributors including age, gender, education, comorbidity, and functional measures, MASLD was associated with an increased risk of persistent physical disability (HR 1.41 [95% CI: 1.07-1.87]) and reduced risk of incident dementia (HR 0.63 [95% CI: 0.48-0.83]). Prevalent MASLD is associated with reduced rates of incident dementia but increased risk of persistent physical disability in initially relatively healthy older adults. Understanding the mechanisms underlying these divergent results to allow appropriate risk stratification and counseling is important.

Exposure to residential green and blue space and the natural environment is associated with a lower incidence of psychiatric disorders in middle-aged and older adults: findings from the UK Biobank

BackgroundThere is increasing evidence for the role of environmental factors and exposure to the natural environment on a wide range of health outcomes. Whether exposure to green space, blue space, and the natural environment (GBN) is associated with risk of psychiatric disorders in middle-aged and older adults has not been prospectively examined.MethodsLongitudinal data from the UK biobank was used. At the study baseline (2006–2010), 363,047 participants (women: 53.4%; mean age 56.7 ± 8.1 years) who had not been previously diagnosed with any psychiatric disorder were included. Follow-up was achieved by collecting records from hospitals and death registers. Measurements of green and blue space modeled from land use data and natural environment from Land Cover Map were assigned to the residential address for each participant. Cox proportional hazard models with adjustment for potential confounders were used to explore the longitudinal associations between GBN and any psychiatric disorder and then by specific psychiatric disorders (dementia, substance abuse, psychotic disorder, depression, and anxiety) in middle-aged and older adults.ResultsDuring an average follow-up of 11.5 ± 2.8 years, 49,865 individuals were diagnosed with psychiatric disorders. Compared with the first tertile (lowest) of exposure, blue space at 300 m buffer [hazard ratio (HR): 0.973, 95% confidence interval (CI): 0.952–0.994] and natural environment at 300 m buffer (HR: 0.970, 95% CI: 0.948–0.992) and at 1000 m buffer (HR: 0.975, 95% CI: 0.952–0.999) in the third tertile (highest) were significantly associated with lower risk of incident psychiatric disorders, respectively. The risk of incident dementia was statistically decreased when exposed to the third tertile (highest) of green space and natural environment at 1000 m buffer. The third tertile (highest) of green space at 300 m and 1000 m buffer and natural environment at 300 m and 1000 m buffer was associated with a reduction of 30.0%, 31.8%, 21.7%, and 30.3% in the risk of developing a psychotic disorder, respectively. Subgroup analysis suggested that the elderly, men, and those living with some comorbid conditions may derive greater benefits associated with exposure to GBN.ConclusionsThis study suggests that GBN has significant benefits for lowering the risk of psychiatric disorders in middle-aged and older adults. Future studies are warranted to validate these findings and to understand the potential mechanistic pathways underpinning these novel findings.