Dementia Hazard Ratio Research Articles

Taiso practice and risk of functional disability and dementia among older adults in Japan: The JAGES cohort study

BackgroundTaiso is a Japanese term encompassing meanings akin to calisthenics. Taiso is a widely used exercise program in Japan but whether it prevents functional disability and dementia remains unclear. This study aimed to elucidate the association between practicing Taiso, especially focusing on the well-known Radio-Taiso, and functional disability and dementia in older adults in Japan. MethodsThis population-based prospective cohort study used data from the Japan Gerontological Evaluation Study (JAGES). The participants were 18,016 people aged 65 years or older who resided in 19 municipalities in Japan and were not certified as needing long-term care at the start of follow-up. The outcomes were all functional disability, moderate-to-severe functional disability, and dementia, during an average of 5.3 years of follow-up. Four groups were created based on type of Taiso practice (None, Radio-Taiso only, Other Taiso only, or Both). The Cox proportional hazards model adjusted for age, sex, equivalized income, educational attainment, household composition, employment status, diseases requiring treatment, activities of daily living, depression, cognitive impairment, and walking duration. ResultsThe analysis included data from 11,219 individuals. The mean age of respondents was 74.2 years and 46.3% were men. Compared with the no-practice group, the Other Taiso only group showed a notably decreased risk of all functional disability (hazard ratio [95% CI] 0.87 [0.78–0.96]). The Other Taiso only group was associated with a significant reduction in the hazard ratio for moderate-to-severe functional disability (0.81 [0.70–0.93]). Decreases in the hazard ratio for dementia were also observed in the Radio-Taiso only (0.82 [0.68–0.9998]) and Other Taiso only groups (0.81 [0.70–0.93]). ConclusionsPracticing Taiso, including Radio-Taiso, may reduce the risk of dementia in older adults, while practicing other types of Taiso may reduce the risk of functional disability.

S6: Junior Research Award Winner: Cognitive impairment and Dementia in Latin American Individuals with Parkinsonism and Parkinson’s Disease: A 10/66 Dementia Research Group Study - Jorge Jesus L. Llibre-Guerra, MD

Background: Limited knowledge exists about the association between Parkinsonism or Parkinson’s disease (PD) and cognitive impairment and dementia in Latin America.Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country cohort in Latin America.Methods: The 10/66 is a prospective, observational cohort study. This population-based cohort study was based in six Latin American countries: Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico, and Peru. The study includes 12,865 participants from six countries, including residents aged 65 years and living in urban and rural catchment areas. Exposures included diagnosed Parkinsonism and PD defined according to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main outcome measure for cross-sectional analysis and dementia was used to measure the prospective association with the exposures. Logistic regression models were used to explore the association between Parkinsonism/PD with cognitive impairment at baseline. Competing risk models were used to assess the prospective association between Parkinsonism/PD with incident dementia accounting for competing risk of mortality. Individual country analyses were combined via fixed-effect meta-analysis.Results: At baseline, the prevalence of cognitive impairment in people with Parkinsonism and PD was 30% and 26.2%, respectively. Parkinsonism (OR 2.2 (95%CI 1.9 – 2.6)) and PD (1.9 (95%CI 1.4 – 2.4)) were individually associated with baseline and incident cognitive impairment after accounting for age, sex, and education, after pooling. In competing risk models, the pooled sub- hazard ratios for dementia in the fixed effect metanalysis were 1.5 (95%CI 1.2 – 1.9) for parkinsonism and 1.5 (95%CI 1.0 – 2.2) for PD.Conclusions: Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia in Latin America. Routine screening for cognitive impairment and dementia with validated tools in PD patients may aid earlier detection of those at greater risk ofadverseoutcomes.

Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study

ObjectiveTo compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in adults aged 40-69 years with type 2 diabetes.DesignPopulation based cohort study.SettingKorean National...

Adult Attention Deficit-Hyperactivity Disorder is associated with Lewy Body Disease and Cognitive Impairment: A prospective cohort Study With 15-year Follow-Up

ObjectivesPast reports have suggested that attention-deficit/hyperactivity disorder (ADHD) may be a risk factor for Lewy body disease (LBD). To confirm this relationship, we conducted the present study. DesignA prospective observational cohort study with a follow-up to 15 years. SettingThe subjects were recruited from cognitive neurology clinics, where they attended for a cognitive complaint or health check-up. ParticipantsTwo groups of subjects: ADHD adults and healthy subjects. MeasurementsThe risk of dementia and LBD was estimated with Kaplan-Meier analysis comparing for the presence or absence of ADHD with the log-rank test. Predictors of conversion were assessed through separate univariate and multivariate Cox regression analyses, adjusting for several variables. ResultsThe baseline sample consisted of 161 subjects with ADHD and 109 without ADHD. At the end of the follow-up, 31 subjects developed dementia, 27 cases in the ADHD group and 4 in comparison group. Dementia with Lewy bodies (DLB) was the most frequent type (N:20) of which 19 corresponded to the ADHD group. The incidence of non-amnestic-MCI in the ADHD group was higher representing 67.1 % of these subjects (N:108), and 17.4% (N:19) of healthy cases. The hazard ratios for dementia and LBD in the multivariate adjusted model were 3.33 (95% CI 1.0915 to 10.1699) and 54.54 (95% CI 7.4849 to 397.5028), respectively in the ADHD group. ConclusionsThis study showed that adult ADHD is independently associated with an increased risk of LBD, dementia, and na-MCI. Future studies should clarify this relationship to develop preventive measures for these patients.

Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study.

The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. Over a median follow-up period of 12.5 years, 5852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.

Association of Anemia with Cognitive Function and Dementia Among Older Adults: The Role of Inflammation.

The association of anemia with cognitive function and dementia remains unclear. We aimed to investigate the association of anemia with cognitive function and dementia risk and to explore the role of inflammation in these associations. Within the UK Biobank, 207,203 dementia-free participants aged 60+ were followed for up to 16 years. Hemoglobin (HGB) and C-creative protein (CRP) were measured from blood samples taken at baseline. Anemia was defined as HGB <13 g/dL for males and <12 g/dL for females. Inflammation was categorized as low or high according to the median CRP level (1.50 mg/L). A subset of 18,211 participants underwent cognitive assessments (including global and domain-specific cognitive). Data were analyzed using linear mixed-effects model, Cox regression, and Laplace regression. Anemia was associated with faster declines in global cognition (β= -0.08, 95% confidence interval [CI]: -0.14, -0.01) and processing speed (β= -0.10, 95% CI: -0.19, -0.01). During the follow-up of 9.76 years (interquartile range 7.55 to 11.39), 6,272 developed dementia. The hazard ratio of dementia was 1.57 (95% CI: 1.38, 1.78) for people with anemia, and anemia accelerated dementia onset by 1.53 (95% CI: 1.08, 1.97) years. The risk of dementia tended to be higher in people with both anemia and high CRP (1.89, 95% CI: 1.60, 2.22). There was a statistically significant interaction between anemia and CRP on dementia risk (p-interaction = 0.032). Anemia is associated with cognitive decline (specifically for processing speed) and increased risk of dementia, especially in people with high inflammation.

Association of Long-term Exposure to Air Pollution and Dementia Risk: The Role of Homocysteine, Methionine, and Cardiovascular Burden.

Growing evidence links air pollution with dementia risk, but the biological mechanisms are largely unknown. We investigated the role played by homocysteine (tHcy) and methionine in this association and explored whether this could be explained by cardiovascular diseases (CVDs). Data were extracted from the ongoing Swedish National study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study. At baseline, 2,512 dementia-free participants were examined up to 2013 (mean follow-up: 5.18 ± 2.96 years). Two air pollutants (particulate matter ≤2.5 μm [PM2.5] and nitrogen oxides [NOx]) were assessed yearly from 1990 until 2013 using dispersion models at residential addresses. The hazard ratio of dementia over air pollution levels was estimated using Cox models adjusted for age, sex, education, smoking, socioeconomic status, physical activity, retirement age, creatinine, year of assessment, and the use of supplements. The total effect of air pollutants on dementia was decomposed into 4 pathways involving tHcy/methionine: (1) direct effect; (2) indirect effect (mediation); (3) effect due to interaction; and (4) effect due to both mediation and interaction. To test whether the association was independent from CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), we repeated the analyses excluding those individuals who developed CVDs. The mean age of the study participants was 73.4 years (SD: 10.4), and 62.1% were female individuals. During an average period of 5 years (mean: 5.18; SD: 2.96 years), 376 cases with incident dementia were identified. There was a 70% increased hazard of dementia per unit increase of PM2.5 during the 5 years before baseline (hazard ratio [HR]: 1.71; 95% CI 1.33-2.09). Overall, 50% (51.6%; 95% CI 9.0-94.1) of the total effect of PM2.5 on dementia was due to mediation of tHcy (6.6%; 95% CI 1.6-11.6) and/or interaction (47.8%; 95% CI 4.9-91.7) with tHcy and 48.4% (p = 0.03) to the direct effect of PM2.5 on dementia. High levels of methionine reduced the dementia hazard linked to PM2.5 by 31% (HR: 0.69; 95% CI 0.56-0.85) with 24.8% attributable to the interaction with methionine and 25.9% (p = 0.001) to the direct effect of PM2.5. No mediation effect was found through methionine. Attenuated results were obtained for NOx. Findings for tHcy were attenuated after excluding those who developed CVDs, while remained similar for methionine. High levels of homocysteine enhanced the dementia risk attributed to air pollution, while high methionine concentrations reduced this risk. The impact of homocysteine on cardiovascular conditions partly explains this association. Alternative pathways other than cardiovascular mechanisms may be at play between methionine and dementia.

#4450 ASSOCIATION OF DEMENTIA AND EXPOSURE OF PROTON PUMP INHIBITORS IN DIABETIC PATIENTS

Abstract Background and Aims Dementia is characterized by a decline in cognition and an increasing inability to live independently. Proton pump inhibitors (PPI) are commonly used to treat gastric or duodenal ulcers. Recently, concern about the risk of dementia and exposure to PPI was noted. However, no known association has previously been reported in patients with diabetes. Method We analyzed data from the Taiwan National Health Insurance Research Database between January 1st, 2002 and December 31st, 2013. A total of 526920 diabetic patients were selected as the study cohort. A 1 to 4 propensity score was used for matching. Results During the follow-up period, 169 (2.2%) patients experienced newly diagnosed dementia compared to 1.7% of the control group. According to univariate analysis, the hazard ratio of dementia when exposed to PPI was 1.98(p = 0.0007). In multivariate analysis, the hazard ratio of exposure to PPI was 1.11 (p = 0.0008). In the sensitivity test, greater than 180 cDDDs were associated with a hazard ratio of 1.5 (p = 0.0006). Conclusion The association between PPI use and dementia was significant in diabetic patients. Therefore, PPI use should be cautious in this population. Further study is needed to clarify the mechanism.

Shift work is significantly and positively associated with dementia: A meta-analysis study.

Shift work may disrupt the sleep and wake cycles and negatively affect physical and mental health. Dementia is a neurodegenerative disorder with progressively declining cognition that is receiving increasing attention. Studies on the association between shift work and dementia are rare. Herein, we conducted a meta-analysis to investigate the association between shift work and dementia. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, and Web of Science databases using a related set of keywords. The inclusion criteria were as follows: (1) adult employees working in a factory, company, or organization; (2) exposure to shift work/non-shift work; and (3) outcome of dementia based on examination or assessment. A meta-analysis using a fixed-effects model was performed. The hazard ratio of dementia was compared between shift workers and non-shift workers. Five studies were included in the quantitative synthesis, and two were selected for further meta-analysis. A random-effects model showed a modest association between shift work and an increase in dementia cases (pooled hazard ratio = 1.13; 95% confidence interval: 1.04-1.23; p = 0.04). This association also occurred in night workers for more than 1 year. Shift work and long-term night work were modestly associated with a higher risk of developing dementia. Avoiding long-term night shifts may be effective in reducing dementia risk. Further studies are required to confirm this hypothesis.

Incident dementia and long-term exposure to constituents offine particle air pollution: A national cohort study in the United States.

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO42-, and NH4+ for both end points (even after adjustments of other constituents), among which BC and SO42- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO42-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

The role of type 2 diabetes in the association between habitual glucosamine use and dementia: a prospective cohort study

BackgroundGrowing evidence has showed an association between habitual glucosamine use and type 2 diabetes (T2D). However, the effect of habitual glucosamine use on risk of dementia remains poorly understood. Our study aimed to examine the association between glucosamine use and risk of dementia and further to identify the mediating role of T2D in the association.MethodsA total of 495,942 participants from UK Biobank who completed a questionnaire on habitual glucosamine use were included at baseline (2006–2010) and then followed up for incidence of dementia until 2020. Cox proportional hazard regressions were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. Markov multi-state models were used to explore the role of incidence of T2D during the follow-up in the association.ResultsOverall, 18.80% of the participants reported habitual use of glucosamine at baseline. A total of 6831 dementia events were recorded during a median follow-up of 11 years. In fully adjusted models, habitual glucosamine use was associated with a significantly lower risk of dementia (HR = 0.87, 95% CI: 0.82–0.93). Multi-state models showed that the association between glucosamine use and dementia was mediated by the incidence of T2D during the follow-up (HR of dementia without T2D: 0.92, 95% CI: 0.86–0.99; HR of post-T2D dementia: 0.79, 95% CI: 0.67–0.93).ConclusionsOur findings reveal that habitual use of glucosamine supplement is associated with a lower risk of dementia, which might be explained by incidence of T2D.

Incident Dementia and Long‐Term Exposure to Constituents of U.S. Fine Particle Air Pollution: A National Cohort Study

AbstractBackgroundGrowing evidence suggests that PM2.5 likely increases the risks of neurological disorders, yet little is known about the relative contributions of different constituents. Understanding constituent‐specific effects are critical to targeting emission reductions of specific sources with the greatest health protection.MethodWe conducted a nationwide population‐based cohort study (2000‐2017), by integrating the Medicare Chronic Conditions Warehouse database and two sets of high‐resolution, multiple‐species, air pollution datasets to investigate the impact of long‐term exposure to PM2.5 constituents on incident dementia and Alzheimer’s disease (AD). and home health‐care claims. Hazard ratios for dementia and AD were estimated using single‐ and multi‐constituent Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration‐response relationships.ResultsOf the 18.5 million dementia and 19.2 million AD individuals within these cohorts, 31.5% and 14.6% developed dementia and AD events, respectively. From the single‐pollutant models, an interquartile range (IQR) increase in PM2.5 mass was associated with an increase in dementia incidence ranging between 6‐7% using two exposure datasets. For different PM2.5 constituents, associations remained significant in black carbon (BC), organic matter (OM), sulfate (SO4 2−), and ammonium (NH4 +). Incident dementia was observed to have the strongest association with increases in exposure to SO4 2− and BC (10‐11% increase and 4‐6% per IQR increase, respectively). Effect estimates for AD were even larger. For both endpoints, all constituents had largely linear concentration‐response relationships in the low exposure range, but most tailed off at high exposure concentrations, particularly for AD.ConclusionOur study suggests that long‐term exposure to PM2.5 is significantly associated with increased incident dementia and AD, and that the different PM2.5 constituents may elicit differential neurotoxicity. Reduction of PM2.5 emissions, especially for the main sources of BC and SO4 2−, may reduce the burden of dementia or AD in the aging US population.

Antipsychotic Medication Risk of Dementia and Death: A Propensity Matched Cohort Study.

This study aimed to compare the incidence of dementia and all-cause mortality up to 20 years post-treatment in an index non-demented cohort between antipsychotic (AP) medication treatment and non-AP treatment groups. All patients in Kaiser Permanente Northern California with a major psychiatric diagnosis between 01/01/1996 and 12/31/2000, age ≥ 50 years, and without dementia diagnosis were included. The study cohort was divided into a "user group", patients treated with AP for ≥ 365 days (n = 1,829), and a "non-user group", propensity score-matched on age, sex, and race (n = 9,145). The association between AP exposure and dementia or mortality during the follow-up period (01/01/2001-12/31/2015) was evaluated using Cox proportional hazard models adjusted for psychiatric diagnosis, comorbidities, and other medications. The user group had a hazard ratio (HR) of 2.2 (CI 1.8-2.7) for dementia and 1.3 (CI 1.2- 1.5) for death. The onset of dementia in the user group was significantly higher in patients aged ≤ 65 years (p < 0.001). The user group was sub-grouped into atypical, typical, and both; HR for dementia was 1.7 (CI 1.2-2.4), 2.5 (CI 1.9-3.1), and 1.8 (CI 1.4-2.4), respectively. Dementia and mortality were significantly higher in patients concurrently treated with benzodiazepine (HR 1.3; CI 1.2-1.5 and HR 1.4; CI 1.3-1.5) or tricyclic antidepressants (HR 1.2; CI 1.1-1.4 and HR 1.1; CI 1.0-1.2), respectively. Our preliminary results reveal an association between AP treatment and increased rates of both dementia and mortality. Future research is needed to substantiate our current findings.

Emulating a target trial of proton pump inhibitors and dementia risk using claims data.

Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling. Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use. In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use. This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk.

Abstract 72: Risk Of Dementia Following First-ever Hemorrhagic Or Ischemic Stroke In The General Population

Objective: To assess risk of dementia after first-ever hemorrhagic or ischemic strokes in three prospective cohort studies (Three City, Framingham Heart Study and Rotterdam Study). Methods: Prospective data on incident hemorrhagic or ischemic strokes and matched stroke free comparison was used for each stroke subtype. 5-year risk of dementia after hemorrhagic or ischemic stroke was assessed using a matched case-cohort design. A random effects meta-analysis was used to combine hazard ratios for each study and variations in risk stratified by APOE ε4 allele were assessed. A direct comparison of risk of dementia after hemorrhagic compared with ischemic strokes was evaluated. In a sensitivity analysis Fine &amp; Gray models were conducted after adjusting for competing deaths and subdistribution hazard ratios were computed. Pre-event and post-event cumulative incidence of dementia at 3, 6, 12, 24, 36 and 60 months were assessed. Results: A total of 4,922 persons, including 247 incident hemorrhagic strokes and 1,427 ischemic strokes were included. The combined hazard ratios of dementia were 2.78 (95% CI 1.28, 6.03) after hemorrhagic and 3.35 (1.51, 7.43) after ischemic stroke compared to stroke free individuals. The combined risk of dementia was 0.71 (0.14, 3.68) after hemorrhagic compared with ischemic stroke. Among individuals with APOE ε4 allele, the risk of dementia was 3.88 (1.16, 12.98) after hemorrhagic stroke and 2.10 (1.28, 3.42) after ischemic stroke compared to stroke-free individuals. The cumulative incidence post-event for hemorrhagic strokes flattened between 6 and 24 months with slight increase thereafter, in-contrast to a steady increase in dementia risk over time after ischemic strokes. Conclusions: No difference was observed in overall 5-year risk of dementia after hemorrhagic or ischemic stroke, while the risk was about 3 times higher compared to stroke-free individuals of similar risk profiles. APOE ε4 allele doubles the risk of dementia among hemorrhagic stroke survivors. Risk of dementia after ischemic stroke follows a stepwise pattern overtime, in contrast, dementia risk after hemorrhagic stroke is highest in the early phase.

Long-Term Variability in Body Weight in Relation to the Risk of Dementia: A Prospective Cohort Study

The prospective association of body weight variability with dementia remains unclear. We aimed to investigate whether long-term variability in body weight is associated with the risk of late-life dementia and to explore their potential temporal relationship using data from a nationwide prospective cohort study of the United States. A total of 5,556 participants free of dementia in 2008 (55.66% women; mean [SD] age, 71.1 [3.1] years) were followed up to 8 years for doctor-diagnosed dementia reported biennially. Body weight variability was assessed as the coefficient of variation utilizing the body weight information collected over 16 years before 2008. Cox proportion hazard model was applied to estimate hazard ratio (HR) of dementia associated with body weight variability. Higher body weight variability was associated with an increased incidence of dementia after controlling for sociodemographic factors, lifestyle, mean body weight, and body weight change. The multi-variable adjusted HR of dementia of the highest quartile of body weight variability was 2.01 (95% CI 1.01-1.87) compared with the lowest. Every 1% increment in variability was associated with a 6.2% higher risk of dementia (HR=1.06, 95%CI 1.04,1.09, p-trend<0.001). Such association was observed for both Alzheimer’s disease and other types of dementia, with stronger association observed when body weight variability was assessed closer to dementia assessment.

Increased risk for dementia in neurofibromatosis type 1

PurposeTo determine the risk for dementia in neurofibromatosis type 1 (NF1) using a Finnish nationwide cohort of individuals with NF1, and data from national registries. MethodsA Finnish cohort of 1,349 individuals with confirmed NF1 according to the US National Institutes of Health (NIH) diagnostic criteria was compared with a control cohort of 13,870 individuals matched for age, sex, and area of residence. Dementia-related hospital visits were retrieved from the Finnish Care Register for Health Care using International Classification of Diseases, 10th revision (ICD-10) diagnosis codes G30 and F00–F03. Purchases of antidementia drugs were queried with Anatomical Therapeutic Chemical (ATC) classification code N06D from the drug reimbursement register maintained by the Social Insurance Institution of Finland. The follow-up spanned 1998–2014. ResultsTotals of 16 and 165 individuals with at least two dementia-related diagnoses or drug purchases were identified in the NF1 and control cohorts, respectively. The hazard ratio for dementia in NF1 was 1.67 (95% confidence interval [CI] 1.00–2.80, P = 0.050). In an analysis stratified by the type of dementia, the risk for Alzheimer disease was increased in NF1 compared to controls with a hazard ratio of 2.88 (95% CI 1.47–5.66, P = 0.002). ConclusionDementia and especially Alzheimer disease are previously unrecognized neurological complications of NF1.

Glucose-Dementia Association Is Consistent Over Blood Pressure/Antihypertensive Groups.

Higher glucose levels are associated with dementia risk in people with and without diabetes. However, little is known about how this association might vary by hypertension status and antihypertensive treatment. Most studies on modifiable dementia risk factors consider each factor in isolation. To test the hypothesis that hypertension and antihypertensive treatments may modify associations between glucose levels and dementia. Analyses of data generated from a research study and clinical care of participants from a prospective cohort of dementia-free older adults, including glucose measures, diabetes and antihypertensive treatments, and blood pressure data. We defined groups based on blood pressure (hypertensive versus not, ≥140/90 mmHg versus <140/90 mmHg) and antihypertensive treatment intensity (0, 1, or ≥2 classes of antihypertensives). We used Bayesian joint models to jointly model longitudinal exposure and time to event data. A total of 3,056 participants without diabetes treatment and 480 with diabetes treatment were included (mean age at baseline, 75.1 years; mean 7.5 years of follow-up). Higher glucose levels were associated with greater dementia risk among people without and with treated diabetes. Hazard ratios for dementia were similar across all blood pressure/antihypertensive treatment groups (omnibus p = 0.82 for people without and p = 0.59 for people with treated diabetes). Hypertension and antihypertensive treatments do not appear to affect the association between glucose and dementia risk in this population-based longitudinal cohort study of community-dwelling older adults. Future studies are needed to examine this question in midlife and by specific antihypertensive treatments.

Mediterranean Diet and Risk of Dementia and Alzheimer's Disease in the EPIC-Spain Dementia Cohort Study.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992–1996 and followed up for a mean (±SD) of 21.6 (±3.4) years. A total of 459 incident cases of dementia were ascertained through expert revision of medical records. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet (rMED) score. Hazard ratios (HR) of dementia by rMED levels (low, medium and high adherence levels: ≤6, 7–10 and ≥11 points, respectively) were estimated using multivariable Cox models, whereas time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Results of the fully adjusted model showed that high versus low adherence to the categorical rMED score was associated with a 20% (HR = 0.80, 95%CI: 0.60–1.06) lower risk of dementia overall and HR of dementia was 8% (HR = 0.92, 0.85–0.99, p = 0.021) lower for each 2-point increment of the continuous rMED score. By sub-types, a favorable association was also found in women for non-AD (HR per 2-points = 0.74, 95%CI: 0.62–0.89), while not statistically significant in men for AD (HR per 2-points = 0.88, 0.76–1.01). The association was stronger in participants with lower education. In conclusion, in this large prospective cohort study MD was inversely associated with dementia incidence after accounting for major cardiovascular risk factors. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification.

Lower Risk of Dementia in Patients With Atrial Fibrillation Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Population-Based Cohort Study.

BackgroundA higher risk of developing dementia is observed in patients with atrial fibrillation (AF). Results are inconsistent regarding the risk of dementia when patients with AF use different anticoagulants. We aimed to investigate the risk of dementia in patients with AF receiving non‐vitamin K antagonist oral anticoagulants (NOACs) compared with those receiving warfarin.Methods and ResultsWe conducted a nationwide population‐based cohort study of incident cases using the Taiwan National Health Insurance Research Database. We initially enlisted all incident cases of AF and then selected those treated with either NOACs or warfarin for at least 90 days between 2012 and 2016. First‐ever diagnosis of dementia was the primary outcome. We performed propensity score matching to minimize the difference between each cohort. We used the Fine and Gray competing risk regression model to calculate the hazard ratio (HR) for dementia. We recruited 12 068 patients with AF (6034 patients in each cohort). The mean follow‐up time was 3.27 and 3.08 years in the groups using NOACs and warfarin, respectively. Compared with the HR for the group using warfarin, the HR for dementia was 0.82 (95% CI, 0.73–0.92; P=0.0004) in the group using NOACs. Subgroup analysis demonstrated that users of NOAC aged 65 to 74 years, with a high risk of stroke or bleeding were associated with a lower risk of dementia than users of warfarin with similar characteristics.ConclusionsPatients with AF using NOACs were associated with a lower risk of dementia than those using warfarin. Further randomized clinical trials are greatly needed to prove these findings.