Higher Incidence Of Dementia Research Articles

Subclinical hyperthyroidism and the risk of dementia: A meta-analysis.

Accumulating evidence suggests that thyroid dysfunction may be related to the risk of dementia. However, previous studies evaluating the association between subclinical hyperthyroidism and the risk of dementia showed inconsistent results. This systematic review and meta-analysis were performed to evaluate the relationship between subclinical hyperthyroidism and the incidence of dementia in the general population. Cohort studies relevant were retrieved by searching the electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Subgroup and meta-regression analyses were performed to investigate the source of heterogeneity. Nine cohort studies including 49,218 community-derived participants were included. Among them, 3177 (6.5%) had subclinical hyperthyroidism at baseline. During a mean follow-up of 10.2 years, 4044 participants developed dementia. The pooled results showed that compared to the participants with euthyroidism, those with subclinical hyperthyroidism had a higher incidence of dementia (risk ratio: 1.38, 95% confidence interval: 1.09 to 1.74, p=.006; I2=47%). Subgroup analyses according to study design, age of the participants, methods for diagnosis of dementia, or analytic model did not significantly change the results. The univariate meta-regression showed that the cutoff of thyroid-stimulating hormone for defining subclinical hyperthyroidism negatively affected the association between subclinical hyperthyroidism and dementia (coefficient: -1.44, p=.009), which completely explained the heterogeneity (residual I2=0%). Subjects with subclinical hyperthyroidism may have a higher risk of dementia compared to those with euthyroidism.

Validation of the delirium diagnostic tool-provisional (DDT-Pro) in geriatric medical inpatients with diagnostic permutations of the 3Ds with and without delirium

ObjectiveValidations of brief delirium tools have not included analysis of psychiatric disorders comorbidities or control groups. We validated the Delirium Diagnostic Tool-Provisional (DDT-Pro) in 422 geriatric inpatients with high incidence of depression and/or dementia. MethodsCross-sectional study using two delirium reference standards, DSM-5-TR and Delirium Rating Scale-Revised-98 (DRS-R98). We assessed concurrent and construct DDT-Pro validity too. ResultsThere were 117 (27.7%) delirium cases using DDT-Pro, 104 (24.6%) per DSM-5-TR and 93 (22.0%) per DRS-R98; 133 patients (31.5%) had depression and 105 (24.9%) dementia, some comorbid with delirium. DDT-Pro accuracy (AUC under ROC curve) ranges were 88.3–95.9% vs DSM-5-TR and 92.7–95.0% vs DRS-R98 for whole sample and four diagnostic groups, without statistical differences. DDT-Pro ≤6 had the most balanced sensitivity-specificity for delirium diagnosis against both DSM-5-TR and DRS-R98 with similar specificity but higher sensitivity for DRS-R98 than DSM-5-TR delirium, with the highest values in patients with depression and dementia (≥92% sensitivity, ≥81% specificity). Positive and negative likelihood ratios support diagnostic strength. Concurrent validity was high reflected by significant correlations (p < 0.001) of DDT-Pro total and item scores with DRS-R98 and Delirium Frontal Index scores, highest in groups with comorbid depression and/or dementia. The DDT-Pro represented a single construct for delirium demonstrated by one factor with high item loadings and high internal consistency reliability of its items. ConclusionsThe DDT-Pro demonstrated strong performance metrics in general hospital elderly inpatients with preexisting depression and/or dementia, which is unique among brief delirium tools. Its optimized cutoff score was the same as in other populations.

Contemporary Incidence of Cognitive Impairment or Dementia in Patients undergoing Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

Despite the high prevalence of cognitive impairment or dementia post coronary artery bypass grafting (CABG), the incidence of cognitive impairment or dementia post-CABG in contemporary practice is currently unclear. Therefore, this paper aims to investigate the incidence and associated risk factors of cognitive impairment or dementia in patients post-CABG. A systematic search across three databases (PubMed, SCOPUS and Embase) was conducted for studies published in or after 2013 that reported cognitive impairment or dementia post-CABG. Subgroup analyses and meta-regression by risk factors were performed to determine their influence on the results. This analysis included 23 studies with a total of 2620 patients. The incidence of cognitive impairment or dementia less than one month, two to six months, and more than twelve months post-CABG was 35.96% (95%CI: 28.22-44.51, I2=87%), 21.33% (95%CI: 13.44-32.15, I2=88%) and 39.13% (95%CI: 21.72-58.84, I2=84%), respectively. Meta-regression revealed that studies with more than 80% of the cohort diagnosed with hypertension were significantly associated with incidence of cognitive impairment or dementia less than one-month post-CABG. This meta-analysis demonstrates a high incidence of cognitive impairment or dementia in patients post-CABG in contemporary practice, particularly less than one month post-CABG. We found that hypertension was a significant risk factor in the short term (less than one month) follow-up period for cognitive impairment or dementia post-CABG. Future research should be done to assess strategies to reduce cognitive impairment post-CABG. .

Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline.

Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention. We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS]). The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score=1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and=1.15 [1.08; 1.22] in carriers; P=0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline. Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia.

Impact of air pollution and climate change on mental health outcomes: an umbrella review of global evidence.

The impact of air pollution and climate change on mental health has recently raised strong concerns. However, a comprehensive overview analyzing the existing evidence while addressing relevant biases is lacking. This umbrella review systematically searched the PubMed/Medline, Scopus and PsycINFO databases (up to June 26, 2023) for any systematic review with meta-analysis investigating the association of air pollution or climate change with mental health outcomes. We used the R metaumbrella package to calculate and stratify the credibility of the evidence according to criteria (i.e., convincing, highly suggestive, suggestive, or weak) that address several biases, complemented by sensitivity analyses. We included 32 systematic reviews with meta-analysis that examined 284 individual studies and 237 associations of exposures to air pollution or climate change hazards and mental health outcomes. Most associations (n=195, 82.3%) involved air pollution, while the rest (n=42, 17.7%) regarded climate change hazards (mostly focusing on temperature: n=35, 14.8%). Mental health outcomes in most associations (n=185, 78.1%) involved mental disorders, followed by suicidal behavior (n=29, 12.4%), access to mental health care services (n=9, 3.7%), mental disorders-related symptomatology (n=8, 3.3%), and multiple categories together (n=6, 2.5%). Twelve associations (5.0%) achieved convincing (class I) or highly suggestive (class II) evidence. Regarding exposures to air pollution, there was convincing (class I) evidence for the association between long-term exposure to solvents and a higher incidence of dementia or cognitive impairment (odds ratio, OR=1.139), and highly suggestive (class II) evidence for the association between long-term exposure to some pollutants and higher risk for cognitive disorders (higher incidence of dementia with high vs. low levels of carbon monoxide, CO: OR=1.587; higher incidence of vascular dementia per 1 μg/m3 increase of nitrogen oxides, NOx: hazard ratio, HR=1.004). There was also highly suggestive (class II) evidence for the association between exposure to airborne particulate matter with diameter ≤10μm (PM10) during the second trimester of pregnancy and the incidence of post-partum depression (OR=1.023 per 1 μg/m3 increase); and for the association between short-term exposure to sulfur dioxide (SO2) and schizophrenia relapse (risk ratio, RR=1.005 and 1.004 per 1 μg/m3 increase, respectively 5 and 7 days after exposure). Regarding climate change hazards, there was highly suggestive (class II) evidence for the association between short-term exposure to increased temperature and suicide- or mental disorders-related mortality (RR=1.024), suicidal behavior (RR=1.012), and hospital access (i.e., hospitalization or emergency department visits) due to suicidal behavior or mental disorders (RR=1.011) or mental disorders only (RR=1.009) (RR values per 1°C increase). There was also highly suggestive (class II) evidence for the association between short-term exposure to increased apparent temperature (i.e., the temperature equivalent perceived by humans) and suicidal behavior (RR=1.01 per 1°C increase). Finally, there was highly suggestive (class II) evidence for the association between the temporal proximity of cyclone exposure and severity of symptoms of post-traumatic stress disorder (r=0.275). Although most of the above associations were small in magnitude, they extend to the entire world population, and are therefore likely to have a substantial impact. This umbrella review classifies and quantifies for the first time the global negative impacts that air pollution and climate change can exert on mental health, identifying evidence-based targets that can inform future research and population health actions.

Systemic inflammation, lifestyle behaviours and dementia: A 10-year follow-up investigation

ObjectivesLifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the underlying mechanisms remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association. MethodsThe sample comprised 3131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52–92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n = 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein in 2012/13. ResultsBinary logistic regression models indicated that the odds of subsequent dementia increased by 1.19 for each additional health-risk behaviour (95% confidence intervals: 1.04, 1.37, p = 0.014) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, and depression. However, this association was not mediated by C-reactive protein. ConclusionsCo-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia.

Heterogeneity in the effect of type 2 diabetes on dementia incidence in a diverse cohort of Asian American and non-Latino White older adults.

Dementia incidence is lower among Asian Americans than among Whites, despite higher prevalence of type 2 diabetes, a well-known dementia risk factor. Determinants of dementia, including type 2 diabetes, have rarely been studied in Asian Americans. We followed 4846 Chinese, 4129 Filipino, 2784 Japanese, 820 South Asian, and 123 360 non-Latino White members of a California-based integrated health-care delivery system from 2002 to 2020. We estimated dementia incidence rates by race/ethnicity and type 2 diabetes status, and we fitted Cox proportional hazards and Aalen additive hazards models for the effect of type 2 diabetes (assessed 5years before baseline) on age of dementia diagnosis, controlling for sex/gender, educational attainment, nativity, height, race/ethnicity, and a race/ethnicity × diabetes interaction. Type 2 diabetes was associated with higher dementia incidence in Whites (hazard ratio [HR] = 1.46; 95% CI, 1.40-1.52). Compared with Whites, the estimated effect of diabetes was larger in South Asians (HR = 2.26; 95% CI, 1.48-3.44), slightly smaller in Chinese (HR = 1.32; 95% CI, 1.08-1.62) and Filipino (HR = 1.31; 95% CI, 1.08-1.60) individuals, and similar in Japanese individuals (HR = 1.44; 95% CI, 1.15-1.81). Heterogeneity in this association across Asian subgroups may be related to type 2 diabetes severity. Understanding this heterogeneity may inform prevention strategies to prevent dementia for all racial and ethnic groups.

Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program

Although poorly controlled diabetes is associated with a higher incidence of dementia, few studies have examined the association of diabetes management interventions with dementia incidence. To examine the association of receiving a multidisciplinary diabetes management program (the Risk Assessment and Management Program-Diabetes Mellitus [RAMP-DM]) that enables better glycemic control with subsequent risk of dementia incidence and the association of dementia with glycemic control. This territory-wide, retrospective, matched cohort study with more than 8 years of follow-up was conducted using electronic health care records from all the patients who used public health care services in Hong Kong from 2011 to 2019. Eligible participants included all patients with type 2 diabetes (T2D) who were managed in primary care settings. Patients who received RAMP-DM were matched in a 1:1 ratio with patients who received usual care only. Data analysis occurred from April 2023 to July 2023. Diagnosis of T2D, hemoglobin A1C (HbA1C) level, and attendance at a general outpatient clinic or family medicine clinic. Patients received either RAMP-DM or usual care. Incidence of all-cause dementia and subtypes of dementia were compared between the RAMP-DM and usual care participants using a Cox proportional hazard model with other baseline characteristics, biomarkers, and medication history adjusted. HbA1C levels were measured as a secondary outcome. Among the 55 618 matched participants (mean [SD] age, 62.28 [11.90] years; 28 561 female [51.4%]; 27 057 male [48.6%]), including the 27 809 patients in the RAMP-DM group and 27 809 patients in the usual care group, patients had been diagnosed with T2D for a mean (SD) of 5.90 (4.20) years. During a median (IQR) follow-up period of 8.4 (6.8-8.8) years, 1938 patients in the RAMP-DM group (6.97%) and 2728 patients in the usual care group (9.81%) received a diagnosis of dementia. Compared with those receiving usual care, RAMP-DM participants had a lower risk of developing all-cause dementia (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.68-0.77; P < .001), Alzheimer disease (aHR, 0.85; 95% CI, 0.76-0.96; P = .009), vascular dementia (aHR, 0.61; 95% CI, 0.51-0.73; P < .001), and other or unspecified dementia (aHR, 0.71; 95% CI, 0.66-0.77; P < .001). Compared with having a mean HbA1C level during the first 3 years after cohort entry between 6.5% and 7.5%, a higher risk of dementia incidence was detected for patients with a 3-year mean HbA1C level greater than 8.5% (aHR, 1.54; 95% CI, 1.31-1.80]), between 7.5% and 8.5% (aHR, 1.33; 95% CI, 1.19-1.48), between 6% and 6.5% (aHR, 1.17; 95% CI, 1.07-1.29), and 6% or less (aHR, 1.39; 95% CI, 1.24-1.57). In this cohort study of patients with T2D, the findings strengthened evidence of an association of glycemic control with dementia incidence, and revealed that a multidisciplinary primary care diabetes management program was associated with beneficial outcomes for T2D patients against dementia and its major subtypes. A moderate glycemic control target of HbA1C between 6.5% and 7.5% was associated with lower dementia incidence.

Cognitive reserve proxies for individuals with intellectual developmental disability: A scoping review

AbstractBackgroundCognitive reserve (CR) has not been studied in people with Intellectual Developmental Disability, a population with a high incidence of dementia. Commonly adopted CR proxies should be adapted to reflect more specifically the experiences of people with Intellectual Developmental Disability.MethodThis scoping review intended to identify CR proxies relevant to people with this condition.ResultsSome of these were the same already detected in a population without intellectual disabilities (education, occupation, physical activity, leisure, community and social activities); others were found to be specifically relevant for this population: type of schooling, parental educational level, environmental stimulation and living place.ConclusionsThese proxies need to be considered in studies on CR and Intellectual Developmental Disability and in clinical practice. Research on the protective effect of CR aims to encourage policies promoting lifestyle‐based educational and preventive interventions and overcome participation barriers for people with Intellectual Developmental Disability.

Anticoagulation Patterns Among Community-Dwelling Older Adults With Atrial Fibrillation.

To assess clinicians' prescribing practices for anticoagulation in older adults with atrial fibrillation or atrial flutter (AF/F) and determine factors common among those without anticoagulation. We performed a community-based retrospective cohort study of adults aged 65 years and older with a history of nonvalvular AF/F to determine the rate of oral anticoagulation utilization. We also assessed for associations between anticoagulation use and comorbid conditions and common geriatric syndromes. A total of 3832 patients with a diagnosis of nonvalvular AF/F were included (mean [SD] age, 79.9 [8.4] years), 2693 (70.3%) of whom were receiving anticoagulation (51.7%, a vitamin K antagonist; 48.1%, a direct-acting oral anticoagulant). Patients with higher Elderly Risk Assessment index (ERA) scores, a surrogate for health vulnerability, received anticoagulation less often than patients with lower scores. The percentage of patients with a history of falling was higher among those who did not receive anticoagulation than among those who did (44.4% vs 32.8%; P < .001). Similarly, a diagnosis of dementia was more common in the no-anticoagulation group than the anticoagulation group (18.5% vs 12.7%; P < .001). A substantial proportion of older adults with AF/F do not receive anticoagulation. Those without anticoagulation had higher risk of health deterioration based on higher ERA scores and had a higher incidence of dementia and fall history. This suggests that the presence of geriatric syndromes may influence the decision to withhold anticoagulation.

PSYCHOSOCIAL RISK, SUBCLINICAL CVD, AND BRAIN VOLUMES: EXAMINING SEX DISPARITIES IN DEMENTIA RISK

Abstract The majority of the sex disparity in dementia remains unexplained. One potential risk factor for women’s higher incidence of dementia is subclinical cardiovascular disease (SCVD), including carotid atherosclerosis and arterial stiffness. To date, there is a significant gap in what is known about sex differences in the impact of psychosocial risk on pre-dementia risk factors both directly and via SCVD. Therefore, this study aimed to examine the mediating influence of SCVD on the relationship between psychosocial risk and brain volumes, as a proxy for pre-dementia risk, and whether the relationship is moderated by sex. The analysis included 136 older adults with a mean age of 68.04y who underwent neuropsychological, psychosocial, and vascular assessment (pulse wave velocity [PWV], carotid intima media thickness [IMT]), and 3T cranial magnetic resonance imaging. Moderated mediation analyses, adjusted for age and education, showed a mediating role of PWV in the relation of loneliness to total brain volumes (global measure of atrophy) was more pronounced among women (average causal mediation effect [ACME]=.44; p=.11). Unadjusted analyses trended toward moderated mediation, such that the mediating role of carotid IMT in the relation of anxiety to total WMLV (ACME=.001; p=.06) and total frontal WML volumes (ACME=.001; p=.05) was more pronounced among women than men. Findings suggest that in women, but not men, psychosocial risk factors may influence brain volumes via subclinical CVD. Additional research is needed to determine if these interrelations help to explain some of the sex disparity in dementia risk.

Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype.

Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown. Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status. After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR]=3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR=2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers. APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk. Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.

Does ethnicity influence dementia, stroke and mortality risk? Evidence from the UK Biobank.

The number of people with dementia and stroke is increasing worldwide. There is increasing evidence that there are clinically relevant genetic differences across ethnicities. This study aims to quantify risk factors of dementia, stroke, and mortality in Asian and black participants compared to whites. 272,660 participants from the UK Biobank were included in the final analysis, among whom the vast majority are white (n = 266,671, 97.80%), followed by Asian (n = 3,790, 1.35%), and black (n = 2,358, 0.84%) participants. Cumulative incidence risk was calculated based on all incident cases occurring during the follow-up of the individuals without dementia and stroke at baseline. We compared the allele frequency of variants in Asian and black participants with the referent ethnicity, whites, by chi-square test. Hierarchical cluster analysis was used in the clustering analysis. Significance level corrected for the false discovery rate was considered. After adjusting for risk factors, black participants have an increased risk of dementia and stroke compared to white participants, while Asians has similar odds to the white. The risk of mortality is not different in blacks and white participants but Asians have a decreased risk. The study provides important insights into the potential differences in the risk of dementia and stroke among different ethnic groups. Specifically, the study found that black individuals had a higher incidence of dementia and stroke compared to white individuals living in the UK. These findings are particularly significant as they suggest that there may be underlying factors that contribute to these differences, including genetic, environmental, and social factors. By identifying these differences, the study helps to inform interventions and policies aimed at reducing the risk of dementia and stroke, particularly among high-risk populations.

Effects of race, baseline cognition, and APOE on the association of affective dysregulation with incident dementia: A longitudinal study of dementia-free older adults

BackgroundAffective symptoms are dementia risk factors. Mild behavioral impairment (MBI) is a neurobehavioral syndrome that refines incorporation of psychiatric symptomatology into dementia prognostication by stipulating symptoms must emerge de novo in later life and persist for ≥6 months. Here, we investigated the longitudinal association of MBI-affective dysregulation with incident dementia. MethodsNational Alzheimer Coordinating Centre participants with normal cognition (NC) or mild cognitive impairment (MCI) were included. MBI-affective dysregulation was operationalized as Neuropsychiatric Inventory Questionnaire-measured depression, anxiety, and elation at two consecutive visits. Comparators had no neuropsychiatric symptoms (no NPS) in advance of dementia. Cox proportional hazard models were implemented to assess the risk of dementia, adjusted for age, sex, years of education, race, cognitive diagnosis, and APOE-ε4 status, with interaction terms as appropriate. ResultsThe final sample included 3698 no-NPS (age:72.8; 62.7 % female), and 1286 MBI-affective dysregulation participants (age:75; 54.5 % female). MBI-affective dysregulation had lower dementia-free survival (p < 0.0001) and greater incidence of dementia (HR = 1.76, CI:1.48–2.08, p < 0.001) versus no NPS. Interaction analyses revealed that MBI-affective dysregulation was associated with higher dementia incidence in Black participants than White (HR = 1.70, CI:1.00–2.87, p = 0.046), NC than MCI (HR = 1.73, CI:1.21–2.48, p = 0.0028), and APOE-ε4 noncarriers than carriers (HR = 1.47, CI:1.06–2.02, p = 0.0195). Of MBI-affective dysregulation converters to dementia, 85.5 % developed Alzheimer's disease, which increased to 91.4 % in those with amnestic MCI. LimitationsMBI-affective dysregulation was not stratified by symptom to further examine dementia risk. ConclusionsEmergent and persistent affective dysregulation in dementia-free older adults is associated with substantial risk for dementia and should be considered in clinical assessments.

Editors' Note: Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period.

In a 2-decade prospective population-based study from Sweden, Dr. Glans and colleagues investigated the association between adherence to conventional dietary recommendations or to a modified Mediterranean diet and subsequent risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or accumulation of AD-related β-amyloid pathology in the CSF, among 28,025 participants. They concluded that these dietary habits were not significantly associated with a reduced risk for developing all-cause dementia, AD dementia, VaD, or AD pathology. In response, Dr. Kawada cites a previous study that found significant interactions between dietary patterns and APOE-ε4 status in relation to incident dementia, with a healthy dietary pattern being associated with lower dementia incidence in ε4 noncarriers and a Western dietary pattern associated with higher dementia incidence in ε4 carriers. Dr. Kawada argues that studies examining the long-term effect of dietary patterns on incident dementia should consider the contribution of genetic factors. In another response, Dr. Hoffman notes that the researchers' use of a modified Mediterranean diet score does not explicitly measure for extra virgin olive oil (EVOO), which may be an important component for maintaining cognitive health, citing epidemiologic and animal studies in this regard. He contends that it is important to consider the role of EVOO as part of a Mediterranean diet for cognitive health to better inform the implementation of this diet in non-Mediterranean countries. Responding to these comments, the authors note that they did not find any significant interaction effects between conventional dietary recommendations or a modified Mediterranean diet and APOE-ε4 status with respect to subsequent dementia but do not comment about the role of extra virgin olive oil. Overall, this exchange highlights enduring uncertainties about the role of specific dietary factors in mitigating the long-term risk of dementia. In a 2-decade prospective population-based study from Sweden, Dr. Glans and colleagues investigated the association between adherence to conventional dietary recommendations or to a modified Mediterranean diet and subsequent risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or accumulation of AD-related β-amyloid pathology in the CSF, among 28,025 participants. They concluded that these dietary habits were not significantly associated with a reduced risk for developing all-cause dementia, AD dementia, VaD, or AD pathology. In response, Dr. Kawada cites a previous study that found significant interactions between dietary patterns and APOE-ε4 status in relation to incident dementia, with a healthy dietary pattern being associated with lower dementia incidence in ε4 noncarriers and a Western dietary pattern associated with higher dementia incidence in ε4 carriers. Dr. Kawada argues that studies examining the long-term effect of dietary patterns on incident dementia should consider the contribution of genetic factors. In another response, Dr. Hoffman notes that the researchers' use of a modified Mediterranean diet score does not explicitly measure for extra virgin olive oil (EVOO), which may be an important component for maintaining cognitive health, citing epidemiologic and animal studies in this regard. He contends that it is important to consider the role of EVOO as part of a Mediterranean diet for cognitive health to better inform the implementation of this diet in non-Mediterranean countries. Responding to these comments, the authors note that they did not find any significant interaction effects between conventional dietary recommendations or a modified Mediterranean diet and APOE-ε4 status with respect to subsequent dementia but do not comment about the role of extra virgin olive oil. Overall, this exchange highlights enduring uncertainties about the role of specific dietary factors in mitigating the long-term risk of dementia.

Vitamin D Insufficiency is Associated with Higher Incidence of Dementia, a Large Community-Based Retrospective Cohort Study.

Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75nmol/l). Patients with vitamin D deficiency (<50nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P-value = 0.05) and the insufficiency groups (77 vs. 81 P-value = 0.05) compared to the reference values (≥75nmol/l). Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels.

Risk of dementia associated with body mass index, changes in body weight and waist circumference in older people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

To determine the relationship of dementia with preceding body mass index (BMI), changes in body weight and waist circumference in older people with type 2 diabetes. In the Edinburgh Type 2 Diabetes Study (1064 men and women with type 2 diabetes, aged 60-75), body weight, waist circumference and BMI were measured at baseline and after 4 years in a subgroup (n= 821). Percentage body weight and waist circumference change over 4 years were calculated. Data on incident dementia was recorded during a median follow-up time of 10.84 years. Survival models considering a range of co-variables and/or death as a competing risk were used to estimate the risks of dementia associated with each weight-related variable. A total of 105 incident dementia events were recorded. When compared with people in the lowest BMI group (<25 kg/m2 ), risk of dementia was lower in intermediate BMI groups (25-29.9kg/m2 , HR 0.44, p= 0.002; 30-34.9kg/m2 , HR 0.41, p= 0.001) and the highest BMI group (≧35 kg/m2 , HR 0.35, p= 0.001). In the weight change subgroup, 78 incident dementia events were recorded between years 4 and 10. Body weight loss over 5% (compared with ≦5%) was associated with higher incidence of dementia (HR 2.06, p= 0.010). The association between waist circumference change and dementia was not significant. Both a lower BMI and weight loss over a period of years are indicative of increased dementia risk for older people with type 2 diabetes, while waist circumference changes may be less informative.

Onset age of diabetes and incident dementia: A prospective cohort study

BackgroundRelationship between age at diagnosis of diabetes and dementia is lacking. The aim of the study was to investigate whether diabetes onset at a younger age was associated with a higher incidence of dementia. Methods466,207 participants free of dementia in the UK biobank (UKB) were included in the analysis. Propensity score matching (PSM) was adopted to match diabetic and non-diabetic participants in different onset age of diabetes groups to evaluate onset age of diabetes and incident dementia. ResultsCompared with non-diabetic participants, diabetes participants had an adjusted hazard ratio (HR) of 1.87 (95 % confidence interval [CI]: 1.73–2.03) for all-cause dementia, 1.85 (95 % CI: 1.60–2.04) for Alzheimer's disease (AD), and 2.86 (95 % CI: 2.47–3.32) for vascular dementia (VD). Among diabetic participants who reported onset age, the adjusted HRs for incident all-cause dementia, AD, and VD were 1.20 (95 % CI: 1.14–1.25), 1.19 (95 % CI: 1.10–1.29), and 1.19 (95 % CI: 1.10–1.28), respectively, per 10 years decrease in age at diabetes onset. After PSM, strength of association between diabetes and all-cause dementia increased with decreasing onset age of diabetes (≥60 years: HR = 1.47, 95 % CI: 1.25–1.74; 45–59 years: HR = 1.66, 95 % CI: 1.40–1.96; <45 years: HR = 2.92, 95 % CI: 2.13–4.01) after multivariable adjustment. Similarly, diabetic participants with onset age <45 years had greatest HRs for incident AD and VD, compared with their matched controls. LimitationsOur results only reflect the characteristics of UKB participants. ConclusionsYounger age at diabetes onset was significantly associated with a higher risk of dementia in this longitudinal cohort study.

Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea

BackgroundScrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data.MethodThis population-based cohort study enrolled patients aged 60–89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer’s disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity.ResultsDuring the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10–1.15, p < 0.001). The Kaplan–Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer’s disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13–1.18, p < 0.001).ConclusionIn conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer’s disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality: A prospective cohort study

BackgroundWhether or not there is targeted pharmacotherapy for dementia, an active and healthy lifestyle that includes physical activity (PA) may be a better option than medication for preventing dementia. We examined the association between leisure-time sedentary behavior (SB) and the risk of dementia incidence and mortality. We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities. MethodsIn the UK Biobank, 484,169 participants (mean age = 56.5 years; 45.2% men) free of dementia were followed from baseline (2006–2010) through July 30, 2021. A standard questionnaire measured individual leisure-time SB (watching TV, computer use, and driving) and PA (walking for pleasure, light and heavy do-it-yourself activity, strenuous sports, and other exercise) frequency and duration in the 4 weeks prior to evaluation. Apolipoprotein E (APOE) genotype data were available for a subset of 397,519 (82.1%) individuals. A Cox proportional hazard model and an isotemporal substitution model were used in this study. ResultsDuring a median 12.4 years of follow-up, 6904 all-cause dementia cases and 2115 deaths from dementia were recorded. In comparison to participants with leisure-time SB <5 h/day, the hazard ratio ((HR), 95% confidence interval (95%CI)) of dementia incidence was 1.07 (1.02–1.13) for 5–8 h/day and 1.25 (1.13–1.38) for >8 h/day, and the HR of dementia mortality was 1.35 (1.12–1.61) for >8 h/day. A 1 standard deviation increment of sedentary time (2.33 h/day) was strongly associated with a higher incidence of dementia and mortality (HR = 1.06, 95%CI: 1.03–1.08 and HR = 1.07, 95%CI: 1.03–1.12, respectively). The association between sedentary time and the risk of developing dementia was more profound in subjects <60 years than in those ≥60 years (HR = 1.26, 95%CI: 1.00–1.58 vs. HR = 1.21, 95%CI: 1.08–1.35 in >8 h/day, p for interaction = 0.013). Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a 6% decreased risk and 9% decreased mortality from dementia, with exercise (e.g., swimming, cycling, aerobics, bowling) showing the strongest benefit (HR = 0.82, 95%CI: 0.78–0.86 and HR = 0.79, 95%CI: 0.72–0.86). Compared with APOE ε4 noncarriers, APOE ε4 carriers are more likely to see a decrease in Alzheimer's disease incidence and mortality when PA is substituted for SB. ConclusionLeisure-time SB was positively associated with the risk of dementia incidence and mortality. Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.