Lower Risk Of Alzheimer's Disease Research Articles

Peripheral Immune Cells Contribute to the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with progressive memory and cognitive loss. Neuroinflammation is a central mechanism involved in the progression of AD. With the disruption of the blood-brain barrier (BBB), peripheral immune cells and inflammatory molecules enter into AD brain. However, the exact relationship between peripheral immune cells and AD remains unknown due to various challenges. This study aimed to investigate the potential causal association between peripheral immune cells and AD by using a two-sample Mendelian randomization (TSMR) analysis. We conducted a TSMR to decipher the causal relationship between AD and 731 types of peripheral immune cell parameters from the TBNK, regulatory T cell (Treg), myeloid cell, monocyte, maturation stages of T cell, dendritic cell (DC), and B cell panels. Various analytical methods were employed, including inverse variance weighting (IVW), MR Egger, and weighted median methods. The Cochran's Q statistic, MR-Egger intercept, and MR-PRESSO tests were used to verify the heterogeneity and horizontal pleiotropy of the results. To further verify our results, we also conducted a replication analysis. The analysis identified CD33 on CD14 + monocyte (OR = 1.03; 95% CI, 1.01-1.04;p = 1.14E-04; adjust-p = 0.042) had an increased risk association for AD, which was verified by the replication study. CD33 on CD33dim HLA DR + CD11b- cell (OR = 1.02; 95% CI, 1.01-1.04;p = 2.87E-04; adjust-p = 0.035) had an increased risk association for AD, while secreting CD4 regulatory T cell %CD4 regulatory T cell (OR = 0.97; 95% CI, 0.96-0.99;p = 1.90E-04; adjust-p = 0.046) and CD25 on switched memory B cell (OR = 0.95; 95% CI, 0.92-0.98;p = 2.87E-04; adjust-p = 0.042) were discovered to be related to a lower risk of AD. However, the causal effect of these three immune cells on AD was insufficiently validated in the replication analysis. The MR analysis suggests a potential causal relationship between peripheral immune cells and the risk of AD. Further extensive research is needed on the specific role of peripheral immune cells in AD.

Understanding Health Beliefs and Health Behaviors in Older Adults at Risk for Alzheimer's Disease.

There are significant public health benefits to delaying the onset of Alzheimer's disease (AD) in individuals at risk. However, adherence to brain healthy behaviors is low. The Health Belief Model proposes that specific beliefs are mediators of behavior change. To characterize health belief measures from the Science of Behavior Change Research Network (SBCRN) in an older adult population and associations between health beliefs, AD risk, and current health behaviors. A total of 172 individuals from the Rhode Island AD Prevention Registry participated. SBCRN health belief measures included assessments of future time perspective, self-efficacy, deferment of gratification, and consideration of future consequences. Outcome measures included individual AD risk index score, dementia risk awareness, and lifestyle behaviors including physical, cognitive, and social activity. Participants who were older had higher scores for AD risk, lower future time perspective, and lower generalized self-efficacy (all at p < 0.001). Higher generalized self-efficacy was related to increased physical activity (p < 0.010). Higher future time perspective (p < 0.001) and generalized self-efficacy (p = 0.48) were associated with lower AD risk score. Subjective cognitive decline (SCD) was associated with lower self-efficacy, ability to delay gratification, and a less expansive future time perspective. Greater self-efficacy and perceived future time remaining were associated with lower AD risk and greater engagement in physical activity. SCD was associated with health beliefs that may negatively affect engagement in positive brain health behaviors. Assessment of and psychoeducation about these intrapersonal health belief constructs may be important targets for behavioral interventions to reduce AD risk.

Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer's Disease Risk: A Retrospective Cohort Proof-of-Concept Study.

Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer's disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted.

Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study.

Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.

The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer’s disease, and vascular dementia: a UK Biobank based prospective cohort study

BackgroundPrior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations. ObjectivesWe aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD) incidence. MethodsWith a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank. ResultsAlthough 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07–1.31) for AD; 1.24 (1.08–1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02–1.19) for AD; 1.15 (1.03–1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively. ConclusionsAlthough our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence.

Identifying the mediating role of inflammation on the relationship between socioeconomic status and Alzheimer's disease: a Mendelian randomization analysis and mediation analysis.

Observational studies have demonstrated a significant association between socio-economic status (SES) and Alzheimer's disease (AD). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian Randomization (MR) approach to investigate the causal relationship between SES and genetic susceptibility to AD, as well as to explore the potential mediation effects of inflammation. Large-scale cohorts based on publicly available genome-wide association study (GWAS) datasets from European populations were employed for conducting the MR study. The primary criterion utilized was the inverse-variance weighting (IVW) model. Heterogeneity and horizontal pleiotropy were assessed. In addition, multivariate MR (MVMR) was utilized to correct the confounders. Moreover, a two-step MR approach was used to evaluate the potential mediating effects of factors on the causal effects between SES and AD. As indicated by the results of the IVW model, educational years (OR = 0.708, 95% CI 0.610-0.821, P < 0.001) and household income (OR = 0.746, 95% CI 0.566-0.982, P = 0.037) was associated with a decreased genetic susceptibility risk for AD. The univariable results showed that the causal effect of educational years on the lower risk of AD remained significant (OR = 0.643, 95% CI 0.467-0.886, P = 0.006). In addition, our findings indicated that C-reactive protein (CRP) played a role in the causal effect of educational years on AD. The proportions of mediation were - 50.08% (95% CI - 92.78; - 7.38%). These findings provided evidence supporting the causal effect of educational attainment lower AD risk, with inflammation playing a mediating role. These findings may inform prevention strategies and interventions directed toward AD. Future studies should explore other plausible biological mechanisms.

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk.

Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem. To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk. Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk. The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively). Our study supports complex interplay between genetics and neuropathology in Parkinson's disease-related cognitive impairment, emphasizing the role of lysosomal polygenic burden. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Education counteracts the genetic risk of Alzheimer's disease without an interaction effect.

Alzheimer's disease (AD) is a major cause of disability and mortality in older adults. This study aimed to investigate the association of AD with education and genetic factors. We conducted a prospective cohort study using data from the UK Biobank. Genetic risk was assessed using a polygenic risk score for AD. The educational level was categorized as either low, intermediate, or high. AD was defined using the International Classification of Diseases and Related Health Problems, 10th revision. Logistic regression models were used to investigate the independent and combined effects of genetic factors and educational levels on the risk of AD. We included 318,535 participants in this study (age: 56.53 ± 8.09 years; male: 44.81%). Compared with a low genetic risk, a high genetic risk was associated with a significantly greater risk of AD (OR = 7.09, 95% CI: 6.09-8.26). A high educational level was associated with a 30% lower risk of AD compared with a low educational level (OR = 0.70, 95% CI: 0.60-0.81). Combining genetic risk and education categories, individuals with a low genetic risk and high educational level had a more than 90% (OR = 0.09, 95% CI: 0.05-0.16) lower risk of AD compared to those with a high genetic risk and low educational level. There was no significant interaction between genetic risk and educational level regarding AD risk (p for interaction = 0.359). Education counteracts the genetic risk of AD, without an interaction effect. Increasing education to reduce the incidence of AD is of same importance across individuals with different genetic risk.

Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study.

Epidemiological studies of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) with Alzheimer's disease (AD) have provided controversial findings. Furthermore, little is known about the association between pure fruit/vegetable juices and AD. The present study aims to estimate the associations of SSBs, ASBs, and pure fruit/vegetable juices with AD, and to evaluate the theoretical effects of replacing SSBs and ASBs with the different consumption of pure fruit/vegetable juices on the risk of AD. This prospective cohort study of the UK Biobank included 206,606 participants aged 39-72years free of dementia at baseline between 2006 and 2010. Dietary intake of SSBs, ASBs, and pure fruit/vegetable juices (naturally sweet juices) were collected using a 24-h dietary recall questionnaire completed between 2009 and 2012. Incident AD was identified by medical and mortality records. Cox proportional hazard models and substitution models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 699 cases of AD were identified over a median follow-up of 9.5years. The consumption of SSBs and ASBs (> 2 units/d) were associated with a higher risk of AD. However, participants who drank > 1-2 units/d of pure fruit/vegetable juices were associated with a lower risk of AD. In substitution models, replacing SSBs with an equivalent consumption of pure fruit/vegetable juices could be associated with a risk reduction of AD.

Association of Thyroid Hormone Medication Adherence With Risk of Dementia.

Recent studies suggest that hypothyroidism is a risk factor for dementia. Based on existing literature, it is unclear if treatment or compliance to treatment is associated with decreased dementia risk in hypothyroidism patients. To determine the association between thyroid hormone medication adherence and risk of dementia. A population-based cohort study following patients with newly diagnosed hypothyroidism until incidence of dementia, death, or December 31, 2020, whichever came earliest. The study comprised 41 554 older adults age 50 and above with newly diagnosed hypothyroidism between 2004 and 2008 who underwent health screening. Risk of dementia was evaluated using multivariable-adjusted Cox proportional hazards regression. Among 5188 men (12.5%) and 36 366 (87.5%) women, 2120 cases of incident dementia were identified. After stratification of the participants according to the interquartile range of the medication possession ratio (MPR), the fourth quartile (highest adherence) showed a 14% lower risk of overall dementia compared with the first quartile (lowest adherence) (adjusted hazard ratio 0.86; 95% CI 0.76-0.97). No consistent association was observed between thyroid hormone medication adherence and vascular dementia. After a dichotomous stratification of the MPR, higher MPR (≥0.8) showed a lower risk of Alzheimer disease (adjusted hazard ratio 0.91; 95% CI 0.84-0.99) than lower MPR (<0.8). Better adherence to thyroid hormone medication may be beneficial in preventing incident dementia, especially Alzheimer disease, in older adults with newly diagnosed hypothyroidism. Along with the resolution of hypothyroid symptoms and the reduction of cardiovascular risk factors, the reduction of dementia risk may be another potential benefit of thyroid hormone medication.

Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer's Disease.

Oxidative stress contributes to pathogenesis and progression of Alzheimer's disease (AD). Higher levels of the dietary antioxidants- carotenoids and tocopherols- are associated with better cognitive functions and lower risk for AD, and lower levels of multiple carotenoids are found in serum and plasma of patients with AD. Although brains donated by individuals with mild cognitive impairment had significantly lower levels of lutein and beta-carotene, previous investigators found no significant difference in carotenoid levels of brains with AD and cognitively normal brains. This study tested the hypothesis that micronutrients are significantly lower in donor brains with AD than in healthy elderly brains. Samples of donor brains with confirmed AD or verified health were dissected into grey and white matter, extracted with organic solvents and analyzed by HPLC. AD brains had significantly lower levels of lutein, zeaxanthin, anhydrolutein, retinol, lycopene, and alpha-tocopherol, and significantly increased levels of XMiAD, an unidentified xanthophyll metabolite. No meso-zeaxanthin was detected. The overlapping protective roles of xanthophylls, carotenes, α- and γ-tocopherol are discussed. Brains with AD had substantially lower concentrations of some, but not all, xanthophylls, carotenes, and tocopherols, and several-fold higher concentrations of an unidentified xanthophyll metabolite increased in AD (XMiAD).

Genetically Proxied CRP (C-Reactive Protein) Levels and Lobar Intracerebral Hemorrhage Risk.

Recent evidence suggests that higher CRP (C-reactive protein) levels are associated with lower risk of Alzheimer disease, speculating that CRP might be involved in Aβ clearance mechanisms. Testing this hypothesis, we explored whether genetically proxied CRP levels are also associated with lobar intracerebral hemorrhage (ICH), commonly caused by cerebral amyloid angiopathy. We used 4 genetic variants within the CRP gene that explain up to 64% of the variance of circulating CRP levels and explored in 2-sample Mendelian randomization analyses associations with risk of any, lobar, and deep ICH (1545 cases and 1481 controls). Higher genetically proxied CRP levels were associated with lower odds of lobar ICH (odds ratio per SD increment in CRP, 0.45 [95% CI, 0.25-0.73]) but not deep ICH (odds ratio, 0.72 [95% CI, 0.45-1.14]). There was evidence of colocalization (posterior probability of association, 72.4%) in the signals for CRP and lobar ICH. Our results provide supportive evidence that high CRP levels may have a protective role in amyloid-related pathology.

Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability.

A growing body of evidence suggests that vitamin supplements play a role in the prevention of cognitive decline. The objective of the present cross-sectional study was to evaluate the relationship between cognitive ability and folic acid, B vitamins, vitamin D (VD) and Coenzyme Q10 (CoQ10) supplementation. The sample consisted of 892 adults aged above 50 who were assessed for their cognitive status in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (China) from July 2019 to January 2022. According to the degree of cognitive impairment, the subjects were divided into a normal control (NC) group, subjective cognitive decline (SCD) group, mild cognitive impairment (MCI) group and Alzheimer's disease (AD) group. The results indicated a lower risk of AD in the daily VD-supplemented subjects with MCI compared to those who were not supplemented; a lower risk of cognitive impairment in those with normal cognitive who consumed VD, folic acid or CoQ10 on a daily basis compared those who did not; and a lower risk of cognitive impairment in subjects with normal cognitive performance who consumed B vitamin supplements, either daily or occasionally, compared to those who did not. The correlation was independent of other factors that potentially affect cognition, such as education level, age, etc. In conclusion, our findings confirmed a lower prevalence of cognitive impairment in those who took vitamins (folic acid, B vitamins, VD, CoQ10) daily. Therefore, we would recommend daily supplementation of vitamins (folic acid, B vitamins, VD, CoQ10), especially group B vitamins, as a potential preventive measure to slow cognitive decline and neurodegeneration in the elderly. However, for the elderly who have already suffered from cognitive impairment, VD supplementation may also be beneficial for their brains.

Multidimensional Assessment of Subjective Well-Being and Risk of Dementia: Findings from the UK Biobank Study.

This study aimed to examine the associations between subjective well-being (SWB) and risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD). We adopted a multidimensional approach to SWB that included the level and breadth of SWB, the latter indicating the extent to which SWB spreads across life domains. Participants (N=171,197; mean age=56.78; SD=8.16 years) were part of the UK Biobank and were followed up to 8.78 years. Domain-general and domain-specific SWB were measured by single items, and the breadth of SWB was indexed with a cumulative score of satisfaction across domains. Dementia incidence was ascertained through hospital and death records. Cox regression was used to examine the association between SWB indicators and risk of all-cause dementia, AD, and VD. General happiness, health and family satisfaction, and satisfaction breadth (satisfaction in multiple domains) were associated with lower risk of all-cause dementia. The associations held after accounting for socio-demographics, health, behavioral, and economic covariates, and depressive symptoms. Health satisfaction and the breadth of satisfaction were also associated with lower risk of AD and VD, with a pattern of slightly stronger associations for VD compared to AD. Some life domains (e.g., health) may be more fruitfully targeted to promote well-being and help protect against dementia, but it is also important to enhance well-being across multiple domains to maximize the protective effects.

Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans.

This study used admixture mapping to prioritize the genetic regions associated with Alzheimer's disease (AD) in African American (AA) individuals, followed by ancestry-aware regression analysis to fine-map the prioritized regions. We analyzed 10,271 individuals from 17 different AA datasets. We performed admixture mapping and meta-analyzed the results. We then used regression analysis, adjusting for local ancestry main effects and interactions with genotype, to refine the regions identified from admixture mapping. Finally, we leveraged in silico annotation and differential gene expression data to prioritize AD-related variants and genes. Admixture mapping identified two genome-wide significant loci on chromosomes 17p13.2 (p=2.2×10-5 ) and 18q21.33 (p=1.2×10-5 ). Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the MINK1, KIF1C, and BCL2. Our ancestry-aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus. We identified two genome-wide significant admixture mapping signals: on chromosomes 17p13.2 and 18q21.33, which are novel in African American (AA) populations. Our ancestry-aware regression approach showed that AA individuals have a lower risk of Alzheimer's disease (AD) if they inherited African ancestry admixture block at the 17p13.2 locus. We found that the overall proportion of African ancestry does not differ between the cases and controls that suggest African genetic ancestry alone is not likely to explain the AD prevalence difference between AA and non-Hispanic White populations.

Impact of Clinical Association Between Gout and Dementia: A Nationwide Population-Based Cohort Study in Korea.

Hyperuricemia might have neuroprotective or neurodegenerative effects on dementia via oxidative stress or inflammatory response regulation. Few studies have explored the association of hyperuricemia or gout with dementia. This retrospective cohort study aimed to investigate the association between gout and dementia in Korea. Altogether, 5,052 gout patients and 25,260 age- and sex-matched controls were selected from the National Health Insurance Service (NHIS)-National Sample Cohort database. The incidence and risk of dementia were evaluated by reviewing the NHIS record. We also performed a subgroup analysis according to age group (age <65 or ≥65 years) using the standard age of 65 years for elderly and nonelderly groups and sex. During follow-up, 81 and 558 participants in the gout and control cohorts developed dementia, respectively. The mean follow-up duration was 4.38 years in gout patients and 4.94 years in controls. Gout patients had a hazard ratio (HR) of 0.79 for overall dementia (95% confidence interval [95% CI] 0.62-1.00) and significantly lower Alzheimer's disease risk (HR 0.73 [95% CI 0.54-0.98]) after adjusting for age, sex, household income, and comorbidities. In subgroup analysis stratified by age and sex, the inverse association between gout and the risk of overall dementia (HR 0.71 [95% CI 0.52-0.97]) and Alzheimer's disease (HR 0.67 [95% CI 0.46-0.97]) were observed in the elderly male group. On the other hand, age- and sex-adjusted analysis showed that the HR for vascular dementia of gout patients was 2.31 (95% CI 1.02-5.25) in the nonelderly male group. Gout decreased the risk of incident Alzheimer's disease-type dementia, especially in elderly patients. The association between gout and dementia risk may differ according to age and disease duration.

Abstract 11865: Statin Decreases Risk of Dementia in Patients With Osteoarthritis: A Population-Based Study Abstract

Emerging evidence suggested osteoarthritis is associated with increasing risk of dementia possibly because of accumulative age-related comorbidity and physical inactivity. Our study investigated whether statin use could reduce risk of dementia in patients with osteoarthritis. Methods Using a territory-wide health care database, we identified all eligible patients with osteoarthritis ( n = 146 933) from 2000 to 2010. Inverse probability of treatment weighting was used to adjust age, sex, comorbidities and concurrent medications between statin nonusers (n = 102 100) and statin users (n = 44 833). The adjusted hazard ratio was calculated using competing risk regression with Cox proportional-hazard model. Results Among all eligible patients, the mean age was 68.3 ± 13.4 years. The median follow-up was 5.6 years (interquartile range: 1.4-10.2 years), and 8247 (5.61%) patients developed dementia. Statin user (vs statin nonuser) was associated with a lower risk of dementia incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.76 ; 95% confidence interval (CI), 0.72-0.80]. Among the subtypes of dementia, statin user (vs statin nonuser) was associated with a lower risk of Alzheimer disease [multivariable adjusted SHR = 0.67 ; 95% CI, 0.60-0.74] as well as vascular dementia [multivariable adjusted SHR = 0.88 ; 95% CI, 0.78-0.99]. This observation remains consistent in patients across all time-weighted LDL levels. Conclusions Our study suggested that statin use is associated with a lower risk of dementia in osteoarthritis patients, irrespective of time-weighted LDL level. In particular, statin user has a lower risk of Alzheimer disease and vascular dementia when compared with statin nonuser.

Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses.

During the last decade, physical activity (PA) (or "exercise") has been identified as one of the main modifiable factors that influence the development of Alzheimer's disease (AD) pathophysiology. We performed an umbrella review to summarize the evidence on the association between PA/exercise and the risk of developing AD risk, and the effect of exercise interventions on the progression of AD. A systematic search was performed in PubMed, SportDiscus, Cochrane Library and Web of Science (March 2022) to identify meta-analyses assessing the association between PA and the incidence of AD, and assessing the effect of exercise interventions on patients with AD. Twenty-one studies were included. The results with strongest evidence revealed the positive effects of PA on AD risk. Specifically, meeting the WHO recommendations for PA was associated with a lower risk of AD. They also revealed positive effects of exercise on cognitive function, physical performance, and functional independence. There is strong evidence of a protective effect of regular PA against AD risk; however, the dose-response association remains unclear. Physical exercise seems to improve several dimensions in patients with AD, although research is warranted to elucidate the exercise characteristics that promote the greatest benefits.

Association of low meal frequency with decreased in vivo Alzheimer’s pathology

Little is known about the association between meal frequency and Alzheimer's disease (AD) in humans. We tested the hypothesis that low meal frequency (LMF) is associated with reduced invivo AD pathology in human brain, and additionally investigated the mediation of serum ghrelin, a hunger-related hormone, for the association. A total of 411 non-demented older adults were systematically interviewed to identify their dietary patterns including meal frequency and underwent multi-modal neuroimaging for cerebral beta-amyloid (Aβ) and tau deposition, glucose metabolism, and cerebrovascular injury. LMF (less than three meals a day) was significantly associated with lower Aβ deposition compared to high meal frequency (HMF). In addition, both LMF and reduced Aβ deposition were significantly related to elevated serum ghrelin. Our findings suggest that LMF may be related to the lower risk of AD through reduced brain amyloid deposition. Additionally, ghrelin appears mediate the association between LMF and lower amyloid deposition.

Body mass index, genetic susceptibility, and Alzheimer's disease: a longitudinal study based on 475,813 participants from the UK Biobank

BackgroundThe association between body mass index (BMI) and Alzheimer's disease (AD) remains controversial. Genetic and environmental factors are now considered contributors to AD risk. However, little is known about the potential interaction between genetic risk and BMI on AD risk.ObjectiveTo study the causal relationship between BMI and AD, and the potential interaction between AD genetic risk and BMI on AD risk.Methods and ResultsUsing the UK Biobank database, 475,813 participants were selected for an average follow-up time of more than 10 years. Main findings: 1) there was a nonlinear relationship between BMI and AD risk in participants aged 60 years or older (p for non-linear < 0.001), but not in participants aged 37–59 years (p for non-linear = 0.717) using restricted cubic splines; 2) for participants aged 60 years and older, compared with the BMI (23–30 kg/m2) group, the BMI (< 23 kg/m2) group was associated with a higher AD risk (HR = 1.585; 95% CI 1.304–1.928, p < 0.001) and the BMI (> 30 kg/m2) group was associated with a lower AD risk (HR = 0.741; 95% CI 0.618–0.888, p < 0.01) analyzed using the Cox proportional risk model; 3) participants with a combination of high AD genetic risk score (AD-GRS) and BMI (< 23 kg/m2) were associated with the highest AD risk (HR = 3.034; 95% CI 2.057–4.477, p < 0.001). In addition, compared with the BMI (< 23 kg/m2), the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD-GRS; 4) there was a reverse causality between BMI and AD when analyzed using bidirectional Mendelian randomization (MR).ConclusionThere was a reverse causality between BMI and AD analyzed using MR. For participants aged 60 years and older, the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD genetic risk. BMI (23–30 kg/m2) may be a potential intervention for AD.