Risk Of Incident Dementia Research Articles

Genetic and lifestyle risks for coronary artery disease and risk of incident dementia

Abstract Background Lifestyle risk factors for coronary artery disease (CAD) have been associated with neurodegeneration and dementia. Whether an underlying genetic risk for the development of CAD further increases this risk, however, remains unclear. Purpose To examine whether an increased genetic risk for CAD is associated with an increased risk of dementia, and to investigate whether lifestyle factors modify these associations. Methods A prospective cohort study of 457,353 participants of European ancestry without dementia at baseline (mean [SD], age 57 [8] years; 55% were female) was conducted within the UK Biobank study. Exposures were a genome-wide polygenic risk score (PRS) for CAD and a modified version of the American Heart Association’s Life’s Essential 8 (LE8) cardiovascular health score comprising four biological (BMI, BP, lipids, glucose) and four lifestyle (smoking status, diet, physical activity, and sleep duration) risk factors previously linked to both CAD and dementia. Dementia diagnoses were obtained from death register and inpatient records. Results 9,337 cases of all-cause dementia were observed over a median 13.9-year follow-up. There were no significant interactions between genetic risk for CAD and lifestyle factors for all-cause dementia, or any other dementia subtype. After adjusting for potential demographic confounders, a higher genetic risk for CAD was associated with elevated risk of developing all-cause dementia (hazard ratio (HR) per 1-SD increase in PRS = 1.08 [95% CI, 1.05-1.10]), Alzheimer’s disease (HR 1.08 [1.03-1.12]), and vascular dementia (HR 1.13 [1.06-1.19]). An unfavourable LE8 cardiovascular health score was also associated with an increased risk of developing all-cause dementia (HR 1.05 [1.02-1.08]), predominantly through its association with vascular dementia (HR 1.14 [1.06-1.22]), as we found no evidence for any associations between LE8 and Alzheimer’s disease (HR 1.00 [0.97-1.02]). Conclusion These findings indicate that a high genetic risk for CAD is associated with an increased risk of developing major dementia subtypes. Regardless of this underlying genetic risk, however, our results suggest that lifestyle interventions designed to reduce the risk of CAD may also reduce one’s risk of developing dementia, particularly in those with underlying vascular pathology.

Dementia in patients with early cardiovascular complications following ischaemic stroke: A neglected complication of the stroke-heart syndrome

Abstract Background Early cardiovascular complications may occur in 20-30% of patients following following ischaemic stroke (stroke-heart-syndrome, SHS). The risk of dementia in patients with SHS remains unexplored. We aimed to quantify the risk of incident dementia in patients with SHS. Methods We conducted a retrospective analysis using a global federated health care network (TriNetX). We included patients who were discharged alive post-ischaemic stroke from 2000 to 2022. These individuals were classified into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute heart failure [HF], acute myocardial infarction [AMI], ventricular fibrillation or flutter [VFF], or Takotsubo disease [TTS]), ie. those with SHS (Group 1) and those with stroke-only (without SHS; Group 2). The primary outcome was the five-year risk of dementia (vascular dementia [F01], dementia in other disease [F02], unspecified dementia [F03], Alzheimer’s disease [G30]). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis after 1:1 propensity score matching (PSM). Results We identified 70,113 patients with SHS (age 67.3±14.0; 42.2% females) and 1,092,540 patients with stroke-only (age 65.2±14.9, 48.1% females). Prior to PSM, patients with SHS were generally older and had a higher prevalence of cardiovascular treatments compared to those without SHS. Following PSM, 70,111 well-balanced patients were considered in each group, however, patients with SHS had a higher risk of dementia compared to patients with stroke-only (HR 1.25, 95%CI 1.20-1.30). Among the SHS complications, the highest dementia risks were associated with acute HF (HR 1.28, 95%CI 1.21-1.36) and AMI (HR 1.24, 95%CI 1.17-1.30), with no significant associations were found for TTS, and VFF. The increased risk of dementia in patients with SHS compared to patients with stroke-only was independent of oral anticoagulant (OAC) use, sex, and age (> or < 75 years) [Figure 1]. Conclusion Stroke-heart syndrome is associated with increased risk of dementia. Innovative strategies to identify and to prevent SHS complications would improve long-term prognosis in patients with recent stroke.

Longitudinal Changes in Peak Expiratory Flow Predict Risk for Incident Dementia.

Impaired respiratory function, measured via peak expiratory flow (PEF), has been associated with increased dementia risk. However, much of the current literature uses cross-sectional measures of PEF, whereas longitudinal relationships between changes in respiratory function and dementia risk are underexplored. Using 10 years of data (2011-2021) from 2,439 adults ages 65 and older in the National Health and Aging Trends Study (NHATS), we examined whether 5-year changes in PEF (2011-2016) were associated with risk for incident dementia over the subsequent 5-year period (2017-2021). PEF slopes for each participant were estimated using linear mixed-effects models and then grouped into quartiles: rapid, moderate, mild, and no declines. Discrete-time Cox proportional hazards models were used to estimate the risk for incident dementia by PEF slope category, while controlling for several health and sociodemographic characteristics. After excluding dementia cases during the exposure window (2011-2016), we identified 338 cases of incident dementia (13.9%) between 2017-2021. Rapid PEF declines between 2011-2016 were associated with 85% higher risk for incident dementia between 2017-2021 compared to those with no declines in PEF (HR=1.85; 95% CI [1.24, 2.76]). Results were robust to several sensitivity analyses. These findings demonstrate that declines in PEF may precede declines in cognition, suggesting that respiratory function may be an important dementia risk factor in older adults. Additionally, these findings highlight the utility of measuring PEF via a peak flow meter, which is a simple and inexpensive measure of respiratory function.

SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes.

Despite the mechanistic potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) to improve neurologic outcomes, the efficacy of SGLT2i in neurodegenerative disorders among patients with type 2 diabetes is not well established. This population-based cohort study aimed to investigate the association of SGLT2i use with risks of incident dementia and Parkinson disease (PD) in patients with type 2 diabetes. This was a retrospective examination of data from a cohort of 1,348,362 participants with type 2 diabetes (≥40 years), who started antidiabetic drugs from 2014 to 2019, evaluated using the Korean National Health Insurance Service Database. Propensity score matching (1:1; SGLT2i to other oral antidiabetic drugs [OADs]) produced a cohort of 358,862 participants. Primary outcomes were the individual incidence of Alzheimer disease (AD), vascular dementia (VaD), and PD. Secondary outcomes were all-cause dementia (AD, VaD, and other dementia) and a composite of all-cause dementia and PD. Cox proportional hazards models were used to investigate the association between SGLT2i use and the risks of dementia and PD. From the 358,862 participants analyzed (mean [SD] age, 57.8 [9.6] years; 58.0% male), 6,837 incident dementia or PD events occurred. Regarding the individual endpoints, SGLT2i use was associated with reduced risks of AD (adjusted hazard ratio [aHR] 0.81, 95% CI 0.76-0.87), VaD (aHR 0.69, 95% CI 0.60-0.78), and PD (aHR 0.80, 95% CI 0.69-0.91) with a 6-month drug use lag period. In addition, use of SGLT2i was associated with a 21% lower risk of all-cause dementia (aHR 0.79, 95% CI 0.69-0.90) and a 22% lower risk of all-cause dementia and PD than use of other OADs (aHR 0.78, 95% CI 0.73-0.83). The association between the use of SGLT2i and the lowered risk of these neurodegenerative disorders was not affected by sex, Charlson Comorbidity Index, diabetic complications, comorbidities, and medications. Sensitivity analysis further adjusting for bioclinical variables from health screening tests, including blood pressure, glucose, lipid profiles, and kidney function, yielded generally consistent results. In this nationwide population-based study, SGLT2i use significantly reduced the risks of neurodegenerative disorders in patients with type 2 diabetes independent of various factors including comorbidities and bioclinical parameters. This study provides Class II evidence that SGLT2 antidiabetic drugs decrease the risk of dementia and PD in people with diabetes.

Impact of dual sensory impairment on the risk of incident dementia: a protocol for a systematic review and meta-analysis

IntroductionStrong evidence supports the importance of potentially modifiable risk factors for dementia, with sensory loss, particularly visual and hearing impairment, being prominent among them. While single sensory impairment has been...

Association between preventive treatment for unruptured intracranial aneurysms and incident dementia: a nationwide population-based cohort study

Preventive treatments for unruptured intracranial aneurysms (UIAs) are used worldwide. However, the long-term effects to cognition have been underestimated. Using representative sample data from the National Health Insurance Service-Senior Cohort database, we compared cumulative risk of incident dementia between two groups: (1) treatment versus observation group, and (2) within the treatment group (surgical versus endovascular treatment). Cox proportional hazard ratios were estimated after applying one-to-one propensity score matching. Subgroup analyses were conducted to investigate interactions between treatment effects and sex, age and history of stroke, respectively. After matching, 3,763 participants were included in each group. The 10-year incidence rates of dementia were 9.82 and 8.68 per 1,000 person-years in the treatment and observation groups, respectively (HR: 1.11, 95% CI: 0.90–1.38, P = 0.33). Furthermore, the risk of incident dementia was not different between the surgical and endovascular treatment groups (HR: 0.98, 95% CI: 0.70–1.37, P = 0.91). In the subgroup analysis, surgical treatment was associated with an increased risk of developing dementia, particularly among male patient (HR: 2.34, 95% CI: 1.04–5.28). Preventive treatment of UIAs appears acceptable in terms of long-term effects to cognition. However, further researches are strongly required to identify the high risk patients of development of dementia.

Associations of metabolic heterogeneity of obesity with the risk of dementia in middle-aged adults: three prospective studies

BackgroundThe associations of different obesity and metabolic phenotypes during midlife with the risk of incident dementia remain unclear. This study aimed to investigate the associations between metabolic heterogeneity of obesity and long-term risk of dementia.MethodsWe conducted prospective analyses from three cohorts, including the UK Biobank (UKB), Atherosclerosis Risk in Communities (ARIC) study, and Framingham Offspring Study (FOS). Eligible participants were those aged 45–65 years with valid assessments of body mass index (BMI) and metabolic status at the study baseline. Obesity was defined as a BMI of ≥ 30.0 kg/m2, while metabolic abnormality was defined as meeting ≥ 2 of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Metabolic heterogeneity of obesity was evaluated based on obesity and metabolic phenotypes and grouped as metabolically normal non-obesity (MNNO), metabolically abnormal non-obesity (MANO), metabolically normal obesity (MNO), and metabolically abnormal obesity (MAO).ResultsIncluded in this study were 295,823 participants aged 56.3 ± 5.9 years from the UKB, 12,547 participants aged 54.0 ± 5.7 years from the ARIC, and 2,004 participants aged 53.9 ± 5.9 years from the FOS. Over 4,348,208 person-years, a total of 6,190 participants (3,601 in the UKB, 2,405 in the ARIC, and 184 in the FOS) developed incident dementia. In the pooled analysis of three cohorts, metabolic abnormality was associated with a hazard ratio (HR) of 1.41 (95% confidence interval [CI]: 1.10–1.80) for dementia, while obesity was associated with an HR of 1.20 (1.03–1.41). Compared with MNNO, individuals with MANO and MAO had increased risks of dementia (pooled HR: 1.33, 95% CI: 1.04–1.71 for MANO and 1.48, 1.16–1.89 for MAO). However, there was no significant difference in the risk of dementia among MNO (pooled HR: 1.10, 95% CI: 0.98–1.24). In addition, participants who recovered from MANO to MNNO had a lower risk of dementia (pooled HR: 0.79, 95% CI: 0.64–0.97), as compared with stable MANO.ConclusionsMetabolic abnormality has a stronger association with dementia than obesity. Metabolically abnormal non-obesity and obesity, but not metabolically normal obesity, are associated with higher risks of incident dementia as compared with metabolically normal non-obesity. Recovering from an abnormal metabolic status to normal reduces the risk of dementia in populations without obesity. Our findings highlight the important role of metabolic status in the development of dementia and recommend the stratified management of obesity based on metabolic status.

Effects of depression and cognitive impairment on increased risks of incident dementia: a prospective study from three elderly cohorts

Depression is usually accompanied with cognitive impairment and increases risk of incident dementia. However, evidence has been limited on the effect size of depression with cognitive impairment and their synergistic effect on future dementia. To explore this, we examined three large cross-country population-based prospective cohorts. Depressive symptoms were assessed by epidemiologic scale, while cognitive impairment was defined by subjective cognitive tests. Dementia was ascertained by self-reported physician-diagnosed conditions. Cox proportional hazard models were employed to determine the hazard ratio (HR) and 95% confidence interval (95% CI), with adjustments of potential confounding variables. Addictive and multiplicative interactions were calculated to evaluate the synergistic effect. A total of 64,706 participants were included at baseline (mean age: 63.9, female: 55.2%), where 4197 (6.5%) individuals had depressive symptoms only, 28,175 (43.5%) individuals had cognitive impairment only, 11,564 (17.9%) individuals had both, and 20,770 (32.1%) individuals had neither. Compared with the neither group, all the other three groups had higher risks of subsequent dementia (depression only: HR 1.65, 95% CI 1.26–2.17; cognitive impairment only: HR 2.71, 95% CI 2.33–3.14; depression with cognitive impairment: HR 3.51, 95% CI 2.95–4.17). There was insignificant additive (RERI, 0.15, 95% CI −0.45–0.75; AP, 0.042, 95% CI −0.13–0.21; SI, 1.06, 95% CI 0.83–1.37) and multiplicative (0.78, 95% CI 0.58–1.06) interaction between depression and cognitive impairment on subsequent dementia. We found depression with cognitive impairment has higher risks of dementia than either condition alone and no significant synergistic effect exists between these two factors.

Sodium-glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase IV Inhibitors and Risk of Dementia Among Patients with Type 2 Diabetes and Comorbid Mental Disorders: A Population-based Cohort Study

AimTo evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia. MethodsUsing the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method. ResultsOver a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12% lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95% CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension. ConclusionsSGLT2 inhibitors versus DPP4 inhibitors were associated with a lower risk of incident dementia in patients with T2D and comorbid mental disorders. Further randomized controlled trials are required to confirm our findings.

Small Vessel Disease Burden Predicts Incident Dementia and Poor Functional Outcome in Independent Outpatients.

Total small vessel disease (SVD) score is used to measure the burden of SVD. This study aimed to clarify the predictive value of total SVD score for incident dementia and functional outcomes in independent outpatients with vascular risk factors. We derived data from a Japanese cohort in which patients underwent magnetic resonance imaging and cognitive examinations. They were followed up until March 2023. The primary outcomes was dementia. Secondary outcome was functional outcomes. We measured a modified Rankin scale (mRS) score at the last visit and defined poor functional outcomes as mRS score ≥3. After excluding those with a mRS score ≥2, Mini-Mental State Examination score in Japanese version < 24, and missing T2* images, 692 patients were included. During a median follow-up period of 4.6 years, dementia occurred in 31 patients. In multivariate analysis, the score 4 group showed a significantly higher risk of incident dementia than the score 0-3 groups (adjusted hazard ratio, 6.25; 95% CI, 1.83-21.40, p = 0.003). The total SVD score was also independently related to poor functional outcome. The total SVD score of 4, and ≥1 could predict dementia and poor functional outcomes, respectively. Our results suggest intensive management of patients with SVD to prevent dementia and to maintain independent activities of daily living.

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial. Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures. Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.

Cardiovascular health, measured using Life's Essential 8, is associated with reduced dementia risk among older men and women.

Dementia poses considerable challenges to healthy aging. Prevention and management of dementia are essential given the lack of effective treatments for this condition. A secondary data analysis was conducted using data from 928 InCHIANTI study participants (55% female) aged 65 years and older without dementia at baseline. Cardiovascular health (CVH) was assessed by the "Life's Essential 8" (LE8) metric that included health behaviors (diet, physical activity, smoking status, sleep duration) and health factors (body mass index, blood lipid, blood glucose, blood pressure). This new LE8 metric scores from 0 to 100, with categorization including "low LE8" (0-49), indicating low CVH, "moderate LE8 (50-79)", indicating moderate CVH, and "high LE8 (80-100)", indicating high CVH. Dementia was ascertained by a combination of neuropsychological testing and clinical assessment at each follow-up visit. Cox proportional hazards models were used to examine associations between CVH at baseline and risk of incident dementia after a median follow-up of 14 years. Better CVH (moderate/high LE8 vs. low LE8) was inversely associated with the risk of incident dementia (hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.46-0.83, p = 0.001). Compared with health factors, higher scores of the health behaviors (per 1 standard deviation [SD]), specifically weekly moderate-to-vigorous physical activity time (per 1 SD), were significantly associated with a lower risk of incident dementia (health behaviors: HR:0.84, CI:0.73-0.96, p = 0.01; physical activity: HR: 0.62, CI: 0.53-0.72, p < 0.001). While longitudinal studies with repeated measures of CVH are needed to confirm these findings, improving CVH, measured by the LE8 metric, may be a promising dementia prevention strategy.

Associations of socioeconomic status and healthy lifestyle with incident dementia and cognitive decline: two prospective cohort studies

Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction. Using data from the Health and Retirement Study (HRS) [2008-2020] and the English Longitudinal Study of Ageing (ELSA) [2004-2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact. A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72-3.69 in the HRS; 1.43, 1.09-1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%-14.6%) and 2.7% (0.5%-14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40-5.38 in the HRS; 2.02, 1.25-3.27 in the ELSA) and accelerated rate of global cognitive decline (β=-0.058 SD/year; 95% CI:-0.073,-0.043 in the HRS; β=-0.049 SD/year; 95% CI:-0.063,-0.035 in the ELSA). Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults. This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research

Abstract Objective Traumatic Brain Injury (TBI) has been purported to increase risk for later developing neurodegenerative disorders (ND). Forensic neuropsychologists are frequently asked to opine on risk for ND after an alleged TBI. We provide an evidence-based foundation to aid forensic practice by summarizing the: role of the neuropsychologist in TBI-related litigation, complexities associated with identifying TBIs in forensic cases, science of TBI in relation to incident dementia, and current scientific evidence for chronic traumatic encephalopathy. Data Selection The most applicable studies to forensic settings are large prospective cohort and population-based cohort studies given their wider generalizability and long periods of follow-up/tracking for outcomes. Data Synthesis Developing ND after TBI is the exception rather than the rule. Only a small subset (&amp;lt; 5%) of individuals with moderate-to-severe TBI, and even fewer (&amp;lt; 1%) with mild TBI, appear to develop ND, and the characteristics that place some at risk remain unclear. Positive evidence for risk of ND after mild TBI is weak and mostly consists of observational studies characterized by methodological limitations. Conclusions Forensic methods used to establish the likely occurrence of TBI are typically more extensive than those used in clinical evaluations, while TBI definitions used in current research are even more rudimentary and inconsistent. Applying clinical research findings regarding TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote TBI/concussion in a causal manner to ND risk is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities).

Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort. We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors. The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD. ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline.

Poststroke seizures and epilepsy increase the risk of dementia among stroke survivors: A population-based study.

With global aging, the occurrence of stroke and associated outcomes like dementia are on the rise. Seizures and epilepsy are common poststroke complications and have a strong connection to subsequent dementia. This study examines the relationship between poststroke seizures (PSS) or poststroke epilepsy (PSE) and dementia using a national health care database. We conducted a retrospective study using data from the Taiwan National Health Insurance Research Database from 2009 to 2020. We identified acute stroke patients from 2010 to 2015, excluding those with pre-existing neurological conditions. Based on age, sex, stroke severity level, and the year of index stroke, patients with PSS or PSE were matched to those without. The main outcome was incident dementia. This study included 62 968 patients with an average age of 63 years, with males accounting for 62.9%. Of them, 60.3% had ischemic strokes, and 39.7% had hemorrhagic strokes. After an average follow-up period of 5.2 years, dementia developed in 15.9% of patients who had PSS or PSE, as opposed to 8.4% of those without these conditions. A time-dependent Fine and Gray competing risk analysis showed that PSS and PSE were significantly associated with dementia across all stroke types. Subgroup analyses revealed significantly increased risk of dementia across all age groups (<50, 50-64, and ≥65 years), sexes, and various stroke severity levels. The link between PSS or PSE and dementia was particularly pronounced in men, with a less distinct correlation in women. The risk of incident dementia was higher in patients with PSS or PSE. The potential for therapeutic interventions for seizures and epilepsy to reduce poststroke dementia underscores the importance of seizure screening and treatment in stroke survivors.

Slow Gait Speed Predicts Incident Dementia, Mortality, and Long-Term Functional Outcome in Cerebral Small-Vessel Disease.

Gait impairment is observed in patients with small vessel disease (SVD); however, the association between gait function and long-term outcome remains unclear. This study aimed to clarify the predictive value of gait function on incident dementia, survival and functional outcome. Data were derived from a Japanese cohort of patients with SVD. This study included 522 participants who underwent 3-m timed up and go test (TUG), and gait speed, TUG time, was divided into tertiles. Magnetic resonance imaging was used to evaluate severity of white matter hyperintensities, lacunes, and medial temporal atrophy. Primary outcome was dementia. All-cause death and functional outcome by modified Rankin scale at the last visit was also evaluated. The median age was 71 years, and median TUG time was 9.91 s. During follow-up period of 4.8 years, 32 cases of dementia occurred. Cox proportional hazard analysis revealed that slow gait speed (TUG time > 10.88 s) was associated with a significantly higher risk of incident dementia than fast (TUG time < 9.03) and middle (TUG time, 9.04-10.87 s) speeds after adjusting risk factors, Mini-Mental State Examination, SVD severity and brain atrophy (adjusted hazard ratio, 2.73; 95% confidence interval, 1.16-6.42, p = 0.022). Slow speed was also associated with mortality and poor functional outcome compared with other speeds (adjusted odds ratio, 4.19; 95% confidence interval 1.92-9.18, p < 0.001). Gait function was associated with incident dementia, mortality and poor functional outcome independently of cognitive function, brain atrophy, and SVD severity.

Association of sodium-glucose cotransporter 2 inhibitors with risk of incident dementia and all-cause mortality in older patients with type 2 diabetes: A retrospective cohort study using the TriNetX US collaborative networks.

Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted. Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality). The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.

Low Intake of Total Antioxidant Nutrients as a Risk Factor for Incident Dementia in Older Adults: The Shanghai Aging Study

Introduction: Previous longitudinal studies reported the impact of antioxidant nutrients (ANs) on cognitive impairment in the older population, but the conclusions were inconsistent. This study aimed to verify the hypothesis that dietary intake of total AN was associated with incident dementia among older individuals. Methods: Community residents without dementia aged ≥60 years were prospectively followed up for an average of 5.2 years in the Shanghai Aging Study. At baseline, daily intakes of total dietary AN (the sum of carotene, vitamin C, vitamin E, lutein, and flavonoids) and energy were calculated based on an interviewer-administered food frequency questionnaire measuring the dietary intake over the past 1 year for each participant. A battery of neuropsychological tests was used to evaluate cognitive function, and a consensus diagnosis of dementia was made according to the DSM-IV criteria at baseline and follow-up. Results: Among 1,550 dementia-free participants, 135 (8.7%) incident dementia cases were identified during the average of 5.2 years of follow-up. Participants with low AN intake (<112 mg/day) had a significantly higher risk of incident dementia than those with high AN intake (≥112 mg/day) (hazard ratio 1.87, 95% confidence interval 1.26–2.77) after adjusting for age, gender, education, obesity, APOE-ε4, hypertension, diabetes, depression, baseline Mini-Mental State Examination score, and total energy intake. The significant association of total AN intake with incident dementia was only found in individuals ≥70 years. Conclusion: Low total AN intake may be a risk factor for incident dementia among older adults. Maintaining sufficient AN intake may be beneficial against age-related cognitive decline.

Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.