Risk Of All-cause Dementia Research Articles

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.

Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study

We aimed to assess the association of tramadol use with the risk of dementia. This population-based retrospective cohort study using the Korean National Health Insurance Service database included a total of 1,865,827 older adult patients aged 60 years or older with common musculoskeletal pain between January 1, 2003, and December 31, 2007. Individuals who were newly dispensed tramadol (N = 41,963) were identified and propensity score–matched with those who were not (N = 41,963). Over a maximum of 14-year follow-up, the incidence rates (events per 1000 person-years) of all-cause dementia were 6.1 for nonusers, 6.2 for those with cumulative tramadol use of 1–14 days, 7.7 for those with 15–90 days of use, and 8.0 for those with > 90 days of use. Longer cumulative duration of tramadol use was associated with an increased risk of all-cause dementia compared with nonuse (1 to 14 days: aHR 1.06, 95% CI 0.96–1.17; 15 to 90 days: aHR 1.14, 95% CI 1.10–1.35; and more than 90 days: aHR 1.18, 95% CI 1.00–1.39; test for trend: P < 0.001). The results showed a similar pattern for Alzheimer’s disease and were robust across subgroup and sensitivity analyses, but not for vascular dementia. This study found that exposure to tramadol was associated with an increased risk of dementia. Taking this potential risk into consideration, clinicians should carefully weigh potential benefits and risks when prescribing tramadol to older adults with musculoskeletal pain.

6700 Risk Of Dementia According To The Reproductive Factors In Postmenopausal Women With Diabetes

Abstract Disclosure: J. Yu: None. K. Han: None. J. Yun: None. S. Lee: None. Risk of dementia according to the reproductive factors in postmenopausal women with diabetes Jin Yu[1], Kyungdo Han[2], Jae-Seung Yun[3], Seung-Hwan Lee[1],[4] [1]Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[2]Department of Statistics and Actuarial Science, Soongsil University[3]Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[4]Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Previous studies have suggested a possible association between endogenous estrogen exposure and decreased risk of cognitive impairment or dementia. We aimed to investigate the impact of reproductive factors on the risk of dementia in women with diabetes. Methods:166,245 postmenopausal women with type 2 diabetes aged over 40 who underwent health examination in 2009 were identified from the National Health Information Database. Information regarding reproductive factors were collected through self-administered questionnaires. Incident dementia was defined using diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression analyses were performed to evaluate the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia according to reproductive factors including age at menarche, age at menopause, reproductive lifespan, parity, and use of hormone replacement therapy (HRT). Results: The mean age and reproductive lifespan were 64.5 ± 8.0 and 33.4 ± 4.7 years, respectively. During the median follow-up of 8.3 years, 25,330 cases of any dementia, including 20,817 cases of Alzheimer's disease and 2,756 cases of vascular dementia were developed. The hazard ratios (95% CI) of all-cause dementia were 1.28 (1.06-1.56) for age at menarche &amp;gt;16 years compared with ≤12 years, 0.71 (0.66-0.77) for age at menopause ≥55 years compared with &amp;lt;40 years, and 0.72 (0.68-0.76) for reproductive lifespan ≥40 years compared with &amp;lt;30 years, respectively. The risk of all-cause dementia was decreased by 11% in women with parity ≥2 compared with 0, and by 16% in women with HRT for more than 5 years compared without HRT. Similar findings were observed for Alzheimer’s disease and vascular dementia. Conclusion: Longer reproductive lifespan was associated with lower risk of dementia in postmenopausal women with diabetes. Presentation: 6/2/2024

Associations of metabolic syndrome with cognitive function and dementia risk: Evidence from the UK Biobank cohort.

To investigate the associations of metabolic syndrome (MetS) with cognitive function, dementia and its subtypes. Based on the participants recruited by UK Biobank, this study aims to investigate the associations of MetS with cognitive function, dementia and its subtypes. Generalized estimating equations, Cox proportional risk models, and multiple linear regression models were respectively used to assess associations between MetS and dementia-related outcomes. Among the 363,231 participants, 95,713 had MetS at baseline. The results showed that MetS was significantly associated with cognitive function related to fluid intelligence and prospective memory at follow-up. Among participants aged ≥60 years, MetS was correlated with elevated risk of all-cause dementia, particularly vascular dementia (VaD) [hazard ratio 1.115 (95% confidence interval: 1.047, 1.187), hazard ratio 1.393 (95% confidence interval: 1.233, 1.575), respectively]. With increasing MetS components, the risk of all-cause dementia and VaD tended to be elevated. MetS has also been associated with dementia-related structural changes in the brain, including alterations in overall brain volume, white matter volume, grey matter volume and white matter integrity. MetS was associated with poorer cognitive performance and might increase the risk of all-cause dementia as well as VaD, but the effect on Alzheimer's disease was not significant. Holistic control of the MetS may benefit the prevention and control of cognitive impairment and dementia.

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

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

Nut consumption is associated with a lower risk of all-cause dementia in adults: a community-based cohort study from the UK Biobank.

This cohort study aimed to analyze the relationship between nut consumption and the risk of all-cause dementia in adults from the United Kingdom (UK). Data from participants in the UK Biobank cohort between 2007-2012 (baseline) and 2013-2023 (follow-up) were analyzed. Baseline information on nut consumption was obtained using the Oxford WebQ 24-h questionnaire. All-cause dementia (i.e. Alzheimer's disease, frontotemporal dementia, or vascular dementia) was assessed at baseline and follow-up through self-reported medical diagnosis, hospitalization, or death records. Hazard regression models were used to estimate the association between nut consumption and the risk of developing all-cause dementia, with adjustments made for sociodemographic, lifestyle, hearing problems, self-rated health, and the number of chronic diseases. Participants with all-cause dementia at baseline were excluded. A total of 50,386 participants (mean age 56.5 ± 7.7years, 49.2% women) were included in the prospective analyses. The incidence of all-cause dementia was 2.8% (n = 1422 cases). Compared with no consumption, daily nut consumption (> 0 to 3 or more handfuls) was significantly associated with a 12% lower risk of all-cause dementia (hazard ratio = 0.88; 95% confidence interval, 0.77-0.99) after 7.1 mean years of follow-up, regardless of the potential confounders considered. No statistically significant interactions were observed between nut consumption and any of the covariates included in the hazard regression models. Stratified analyses revealed that nut consumption of up to 1 handful of 30g/day and consumption of unsalted nuts were associated with the greatest protective benefits. The daily consumption of nuts may play a protective role in the prevention of dementia.

Dietary patterns and cardiorespiratory fitness in midlife and subsequent all-cause dementia: findings from the Cooper Center Longitudinal Study

BackgroundIdentifying lifestyle factors that independently or jointly lower dementia risk is a public health priority given the limited treatment options available to patients. In this cohort study, we examined the associations between Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet adherence and cardiorespiratory fitness (CRF) with later-life dementia, and assessed whether the associations between dietary pattern and dementia are modified by CRF.MethodsData are from 9,095 adults seeking preventive care at the Cooper Clinic (1987–1999) who completed a 3-day dietary record and a maximal exercise test. Alzheimer’s disease and related disorders or senile dementia (i.e., all-cause dementia) was identified from Medicare administrative claims (1999–2019). Illness-death models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between Mediterranean or DASH diet adherence (primary exposure), CRF (secondary exposure), and all-cause dementia, adjusted for demographic and clinical factors. An interaction term was included between diet score and CRF to assess effect modification by CRF.ResultsThe mean age at baseline was 50.6 (standard deviation [SD]: 8.4) years, and a majority of the study sample were men (77.5%) and White (96.4%). 1449 cases of all-cause dementia were identified over a mean follow-up of 9.2 (SD: 5.8) years. Neither Mediterranean nor DASH diet adherence was associated with dementia risk in fully adjusted models (HR per SD of Mediterranean diet score: 1.00, 95% CI: 0.94, 1.05; HR per SD of DASH diet score: 1.02, 95% CI: 0.96, 1.08). However, participants with higher CRF had a decreased hazard of dementia (HR, per metabolic equivalent of task [MET] increase, Mediterranean model: 0.95, 95% CI: 0.92, 0.98; HR, per MET increase, DASH model: 0.96, 95% CI: 0.92, 0.97). No effect modification by CRF was observed in the association between diet and dementia.ConclusionsIn this sample of apparently healthy middle-aged adults seeking preventive care, higher CRF at midlife was associated with a lower risk of all-cause dementia, though adherence to a Mediterranean or DASH diet was not, and CRF did not modify the diet-dementia association. CRF should be emphasized in multimodal interventions for dementia prevention and investigated among diverse samples.

Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study

BackgroundPrevious research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.MethodsUsing 2005–2021 data from the National Alzheimer’s Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model.ResultsOf 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7).ConclusionsOur studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

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

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

Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis.

Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.

Investigating Modifiable Risk Factors Across Dementia Subtypes: Insights from the UK Biobank.

This study investigates the relationship between modifiable risk factors and dementia subtypes using data from 460,799 participants in the UK Biobank. Utilizing univariate Cox proportional hazards regression models, we examined the associations between 83 modifiable risk factors and the risks of all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Composite scores for different domains were generated by aggregating risk factors associated with ACD, AD, and VD, respectively, and their joint associations were assessed in multivariable Cox models. Additionally, population attributable fractions (PAF) were utilized to estimate the potential impact of eliminating adverse characteristics of the risk domains. Our findings revealed that an unfavorable medical history significantly increased the risk of ACD, AD, and VD (hazard ratios (HR) = 1.88, 95% confidence interval (95% CI): 1.74-2.03, p < 0.001; HR = 1.80, 95% CI: 1.54-2.10, p < 0.001; HR = 2.39, 95% CI: 2.10-2.71, p < 0.001, respectively). Blood markers (PAF = 12.1%; 17.4%) emerged as the most important risk domain for preventing ACD and VD, while psychiatric factors (PAF = 18.3%) were the most important for preventing AD. This study underscores the potential for preventing dementia and its subtypes through targeted interventions for modifiable risk factors. The distinct insights provided by HR and PAF emphasize the importance of considering both the strength of the associations and the population-level impact of dementia prevention strategies. Our research provides valuable guidance for developing effective public health interventions aimed at reducing the burden of dementia, representing a significant advancement in the field.

Microvascular disease and its association with dementia in patients with type 2 diabetes: A nationwide cohort study in Taiwan.

To assess the likelihood of dementia in individuals with type 2 diabetes (T2D), distinguishing between those with and without microvascular diseases. Leveraging the National Health Insurance Research Database in Taiwan, we identified individuals newly diagnosed with T2D from 1 January 2009 through 31 December 2014. Multivariable Cox proportional hazard models were used to compare the risk of outcomes. Individuals with microvascular disease had a significantly higher risk of all-cause dementia (adjusted hazard ratio [95% confidence interval] 1.13 [1.09, 1.17]) compared with matched individuals without microvascular disease. In addition, individuals with diabetic kidney disease and diabetic neuropathy were associated with a significantly increased risk of Alzheimer's disease (1.16 [1.02, 1.32] and 1.14 [1.03, 1.27]), vascular dementia (1.21 [1.06, 1.38] and 1.14 [1.02, 1.28]) and other dementia (1.11 [1.04, 1.19] and 1.10 [1.04, 1.16]), respectively, compared with those without microvascular disease. This nationwide cohort study showed that patients with T2D and microvascular disease, particularly diabetic kidney disease and diabetic neuropathy, were associated with a significantly higher risk of Alzheimer's disease, vascular dementia, other dementia and all-cause dementia than those without microvascular disease.

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

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66-0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45-0.85) for AD and 0.56 (95% CI: 0.36-0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61-0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39-0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68-0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.

Nonarteritic Anterior Ischemic Optic Neuropathy and the Risk of Dementia: A Nationwide Cohort Study.

While emerging theories suggest that vascular dysfunction may occur concurrently with the amyloid cascade in Alzheimer disease (AD) pathogenesis, the role of vascular components as primary neurodegeneration triggers remains uncertain. The aim of this retrospective, population-based cohort study conducted in Korea was to explore the link between nonarteritic anterior ischemic optic neuropathy (NAION) and dementia risk. In this nationwide, population-based, retrospective cohort study, we identified newly diagnosed NAION from 2010 to 2017 in the Korean National Health Insurance Service database. The primary outcome was new dementia diagnoses confirmed by new ICD-10 claims coupled with antidementia medication prescriptions. We assessed dementia risk using hazard ratios (HRs) with 95% CIs over an average 2.69-year follow-up after a 1-year lag period. The cohort consisted of 42,943 patients with NAION and 214,715 age-matched and sex-matched controls without NAION (mean age 61.37 years ± 10.75 SD, 55.48% female). The study found a higher risk of all-cause dementia (ACD; HR 1.28, 95% CI 1.20-1.36), AD (HR 1.27, 95% CI 1.18-1.36), vascular dementia (VaD; HR 1.31, 95% CI 1.09-1.58), and other dementia (HR 1.39, 95% CI 1.11-1.73) among patients with NAION, regardless of other potential confounding factors such as age, sex, lifestyle behaviors, economic status, and preexisting health conditions. In subgroup analysis, the associations between NAION and ACD were stronger in the younger age group (HR 1.83 for those younger than 65 years vs 1.23 for those 65 years or older; p for interaction <0.001). Moreover, the association of NAION with both ACD and VaD was particularly strong among current smokers. We found a significant association between NAION and increased risk for ACD, AD, VaD, and other dementia even after adjusting for potential confounders such as lifestyle, health conditions, and demographic factors within a nationwide cohort. This study highlights the potential role of vascular pathology in dementia progression and suggests that NAION may serve as a robust predictor for dementia, highlighting the need for comprehensive neurologic assessment in patients with NAION. Further research is needed to clarify the association between NAION and dementia risk.

Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. Hepatitis C (hazard ratio=3.33, p=0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

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

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

The Effect of Temporal Persistence of Loneliness on Dementia: A Longitudinal Analysis From the Hunter Community Study.

Loneliness is common and becoming a public health concern. Although there is the clear evidence of the variable effect of temporal differences in loneliness (transient/situational and persistent/chronic) on health, their effect on dementia risk is unclear. This study aims to assess the effect of transient/situational and persistent/chronic loneliness on dementia risk. Participants aged 55years and older from the Hunter Community Study were recruited. Loneliness was measured using a single item measure. Dementia was defined as per International Classification of Disease-10 (ICD 10) codes. The Fine-Gray subdistribution hazard model was performed to calculate dementia risk. Of 1968 total participants with mean age of 66years, (3%) 57 developed dementia and (7%) 135 died over the mean follow up of 10years. Both persistent/chronic and transient/situational loneliness significantly increased the risk of all cause dementia in adjusted models (HR 2.74, 95% CI 1.11-6.88, p 0.03 and HR 2.35, 95% CI 1.21-4.55, p 0.01 respectively) with mean time to event of 9.7years. Feeling lonely below the age of 70years elevated the risk of dementia in later life (HR 4.01, 95% CI 1.40-11.50, p 0.01). Loneliness (both persistent/chronic and transient/situational) was associated with increased risk of all cause dementia, especially if loneliness was experienced before the age of 70years. These results suggest that promoting coping strategies for loneliness especially in persons 70years and younger may play a role in preventing dementia.

The effect of anxiety on all-cause dementia: A longitudinal analysis from the Hunter Community Study.

Anxiety is common, however, the effect of chronicity of anxiety on dementia has not been explored. This study aims to assess the longitudinal relationship between chronic versus resolved versus new onset anxiety, and all-cause dementia risk. A total of 2132 participants with mean age 76 years from the Hunter Community Study were recruited. Anxiety was measured using Kessler Psychological Distress Scale (K10). Dementia was defined as per International Classification of Disease-10 codes. The Fine-Gray subdistribution hazard model was computed to assess dementia risk, while adjusting for the competing risk of death. Chronic anxiety and new onset anxiety at follow-up were associated with all-cause dementia risk (HR 2.80, 95% CI 1.35-5.72 and HR 3.20, 95% CI 1.40-7.45 respectively) with an average time to dementia diagnosis of 10 years (SD = 1.7) whereas resolved anxiety was not. In subgroup analyses, these results were driven particularly by chronic and new anxiety among participants below the age of 70 years (HR 4.58, 95% CI 01.12-18.81 and HR 7.21, 95%CI 1.86-28.02 respectively). Sensitivity analyses imputing missing data and addressing reverse causation gave very similar results. Chronic and new anxiety were associated with increased risk of all-cause dementia, and this association was significant in those 70 years and younger. However, the resolved anxiety at follow-up reduced the risk, similar to that of the non-exposed group. These results suggest that timely management of anxiety may be a viable strategy in reducing the risk of dementia.

Associations of sugar intake, high-sugar dietary pattern, and the risk of dementia: a prospective cohort study of 210,832 participants

BackgroundLimited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population.MethodsA total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer’s disease. Explorative mediation analyses were conducted to explore underlying mechanisms.ResultsIncreased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002–1.004], p < 0.001) and Alzheimer’s disease (1.002, [1.001–1.004], 0.005). Relative sugar intake (%g/kJ/day) also demonstrated significant associations with all-cause dementia (1.317, [1.173–1.480], p < 0.001) and Alzheimer’s disease (1.249, [1.041–1.500], 0.017), while the high-sugar dietary score was only significantly associated with a higher risk of all-cause dementia (1.090, [1.045–1.136], p < 0.001). In addition, both sugar intake and high-sugar dietary score demonstrated significant non-linear relationships with all-cause dementia and Alzheimer’s disease (all p values for non-linearity < 0.05).ConclusionsOur study provided evidence that excessive sugar intake was associated with dementia. Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia.

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

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