Risk Of Alzheimer's Disease Dementia Research Articles

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.

Melatonin: A potential nighttime guardian against Alzheimer's.

In the context of the escalating global health challenge posed by Alzheimer's disease (AD), this comprehensive review considers the potential of melatonin in both preventive and therapeutic capacities. As a naturally occurring hormone and robust antioxidant, accumulating evidence suggests melatonin is a compelling candidate to consider in the context of AD-related pathologies. The review considers several mechanisms, including potential effects on amyloid-beta and pathologic tau burden, antioxidant defense, immune modulation, and regulation of circadian rhythms. Despite its promise, several gaps need to be addressed prior to clinical translation. These include conducting additional randomized clinical trials in patients with or at risk for AD dementia, determining optimal dosage and timing, and further determining potential side effects, particularly of long-term use. This review consolidates existing knowledge, identifies gaps, and suggests directions for future research to better understand the potential of melatonin for neuroprotection and disease mitigation within the landscape of AD.

The Association between Exposure to Fine Particulate Matter and MRI-Assessed Locus Coeruleus Integrity in the Vietnam Era Twin Study of Aging (VETSA).

Increased exposure to ambient air pollution, especially fine particulate matter () is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. Our aim was to investigate if exposure to was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. We examined the relationship between and invivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio () in 381 men [; standard deviation ] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. Multiple linear regressions revealed a significant association between and rostral-middle (; ), whereby higher exposure to was associated with lower . A co-twin control analysis found that, within monozygotic pairs, individuals with higher exposure showed lower (; ), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between and caudal or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.

A Narrative Review of Alzheimer Dementia in African American and Hispanic Populations: The Health Care Provider's Role

African Americans and Hispanics, especially those of advanced age living with chronic diseases, have a higher risk of developing Alzheimer dementia (AD). Poor control of chronic diseases, such as diabetes, lack of awareness of increased risk factors by health care providers, or fragmented provider care can lead to missed opportunities to adopt early assessment strategies that can mitigate the effects or onset of AD. Nurse practitioners and other health care providers can play a crucial role in implementing chronic disease management strategies and educating patients who are at risk for AD among African Americans and Hispanics.

Association of Egg Intake With Alzheimer’s Dementia Risk in Older Adults: The Rush Memory and Aging Project

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer’s dementia and AD is unknown. ObjectivesTo examine the association of egg consumption with Alzheimer’s dementia risk among the Rush Memory and Aging Project cohort. MethodsDietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants’ first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer’s dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer’s dementia. ResultsThis study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer’s dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer’s dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer’s dementia was mediated through dietary choline. ConclusionsThese findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer’s dementia and AD pathology, and the association with Alzheimer’s dementia is partially mediated through dietary choline.

Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle-aged males at high Alzheimer's risk.

High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. A total of 204 healthy middle-aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes. In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (β = -0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage was associated with lower global cognition (males: β = -0.27, p = 0.03; females: β = 0.01, p = 0.93) executive function (males: β = -0.27, p = 0.03; females: β = 0.02, p = 0.87), episodic memory (males: β = -0.28, p = 0.03; females: β = 0.07, p = 0.48), and inferior frontal gyrus volume (males: β = -0.28, p = 0.02; females: β = 0.10, p = 0.33). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females. In middle-aged males at high Alzheimer's dementia risk, but not in females, higher pancreatic fat was associated with lower cognition and brain volumes. These findings suggest a potential sex-specific link between distinct abdominal fat with brain health.

The Predictive Ability of Blood Neurofilament Light Chain in Predicting Cognitive Decline in the Alzheimer's Disease Continuum: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset. Identifying candidate predictors to forecast AD dementia risk before disease onset is crucial for early diagnosis and treatment. We aimed to assess the predictive ability of blood neurofilament light (NfL) chain in anticipating cognitive decline in the AD continuum. We systematically searched PubMed, Web of Science, and Embase from inception until April 7, 2023. Longitudinal observational studies examining the association between baseline blood NfL and cognitive decline or clinical disease conversion were included based on inclusion/exclusion criteria. The final effect size was represented by adjusted hazard ratios (HR) or standardized beta (s.β) coefficients with a 95% confidence interval (CI). A total of 2,862 articles were identified, and 26 studies were included in this meta-analysis. The results indicated that baseline blood NfL could predict cognitive decline, with MMSE [s.β= -0.17, 95% CI (-0.26, -0.07)]; PACC [s.β= -0.09, 95% CI (-0.16, -0.03)]; ADAS-cog [s.β= 0.21, 95% CI (0.13, 0.29)]; CDR-SOB [s.β= 0.27, 95% CI (0.03, 0.50)]; Global cognitive composite [s.β= -0.05, 95% CI (-0.08, -0.01)]; Memory subdomain [s.β= -0.06, 95% CI (-0.09, -0.03)]; Language subdomain [s.β= -0.07, 95% CI (-0.10, -0.05)]; Executive function subdomain [s.β= -0.02, 95% CI (-0.03, -0.01)]; Visuospatial subdomain [s.β= -0.06, 95% CI (-0.08, -0.04)]. Additionally, baseline blood NfL could predict disease progression (conversion from CU/SCD/MCI to MCI/AD) in the AD continuum [Adjust HR = 1.32, 95% CI (1.12, 1.56)]. Baseline blood NfL demonstrated predictive capabilities for global cognition and its memory, language, executive function, visuospatial subdomains decline in the AD continuum. Moreover, it exhibited the potential to predict disease progression in non-AD dementia participants.

Machine Learning Models of Polygenic Risk for Enhanced Prediction of Alzheimer Disease Endophenotypes.

Alzheimer disease (AD) has a polygenic architecture, for which genome-wide association studies (GWAS) have helped elucidate sequence variants (SVs) influencing susceptibility. Polygenic risk score (PRS) approaches show promise for generating summary measures of inherited risk for clinical AD based on the effects of APOE and other GWAS hits. However, existing PRS approaches, based on traditional regression models, explain only modest variation in AD dementia risk and AD-related endophenotypes. We hypothesized that machine learning (ML) models of polygenic risk (ML-PRS) could outperform standard regression-based PRS methods and therefore have the potential for greater clinical utility. We analyzed combined data from the Mayo Clinic Study of Aging (n = 1,791) and the Alzheimer's Disease Neuroimaging Initiative (n = 864). An AD PRS was computed for each participant using the top common SVs obtained from a large AD dementia GWAS. In parallel, ML models were trained using those SV genotypes, with amyloid PET burden as the primary outcome. Secondary outcomes included amyloid PET positivity and clinical diagnosis (cognitively unimpaired vs impaired). We compared performance between ML-PRS and standard PRS across 100 training sessions with different data splits. In each session, data were split into 80% training and 20% testing, and then five-fold cross-validation was used within the training set to ensure the best model was produced for testing. We also applied permutation importance techniques to assess which genetic factors contributed most to outcome prediction. ML-PRS models outperformed the AD PRS (r2 = 0.28 vs r2 = 0.24 in test set) in explaining variation in amyloid PET burden. Among ML approaches, methods accounting for nonlinear genetic influences were superior to linear methods. ML-PRS models were also more accurate when predicting amyloid PET positivity (area under the curve [AUC] = 0.80 vs AUC = 0.63) and the presence of cognitive impairment (AUC = 0.75 vs AUC = 0.54) compared with the standard PRS. We found that ML-PRS approaches improved upon standard PRS for prediction of AD endophenotypes, partly related to improved accounting for nonlinear effects of genetic susceptibility alleles. Further adaptations of the ML-PRS framework could help to close the gap of remaining unexplained heritability for AD and therefore facilitate more accurate presymptomatic and early-stage risk stratification for clinical decision-making.

Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer's disease dementia.

Brain glucose hypometabolism is a preclinical feature of Alzheimer's disease (AD). Dietary omega-3 fatty acids promote brain glucose metabolism, but clinical research is incipient. Circulating omega-3s objectively reflect their dietary intake. This was a cross-sectional study in 320 cognitively unimpaired participants at increased risk of AD dementia. Using lipidomics, we determined blood docosahexaenoic (DHA) and alpha-linolenic (ALA) acid levels (omega-3s from marine and plant origin, respectively). We assessed brain glucose metabolism using [18-F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Blood ALA directly related to FDG uptake in brain areas known to be affected in AD. Stronger associations were observed in apolipoprotein E ε4 carriers and homozygotes. For DHA, significant direct associations were restricted to amyloid beta-positive tau-positive participants. Blood omega-3 directly relate to preserved glucose metabolism in AD-vulnerable brain regions in individuals at increased risk of AD dementia. This adds to the benefits of omega-3 supplementation in the preclinical stage of AD dementia. Blood omega-3s were related to brain glucose uptake in participants at risk of Alzheimer's disease (AD) dementia.Complementary associations were observed for omega-3 from marine and plant sources.Foods rich in omega-3 might be useful in early features of AD.

Diffusion Tensor Imaging in Alzheimer's Studies.

In this chapter, we describe the use of quantitative metrics of white matter obtained from the diffusion tensor model based on diffusion-weighted imaging in Alzheimer's disease (AD). Our description synthesizes insights not only frompatient populations with AD dementia but also from participants at risk for AD dementia (e.g., amnestic mild cognitive impairment, subjective cognitive decline, or familial AD mutation carriers). A reference to studies examining correlations with behavioral variables is also included. Our main message is to caution against the overinterpretation of diffusion metrics and to favor analyses that focus on regions of interest or major white matter tracts for biomarker studies in AD.

Pronoun use in preclinical and early stages of Alzheimer's dementia

The present study aims at improving the predictive power of the use of pronouns in computational modeling of the risk of Alzheimer's dementia (AD) by (i) further determining the onset of increased pronoun use in AD and (ii) providing insights into the linguistic contexts affected by the increase early on. Pronoun use was compared longitudinally between subjects who either stayed cognitively intact (CTR-group, n = 5) or who had developed AD upon follow-up after 10–12 years (AD-group, n = 5). Data were taken from semi-structured biographical interviews, which stem from the Interdisciplinary Longitudinal Study on Adult Development and Aging (ILSE). The first interview (baseline) was conducted when all participants were still cognitively healthy. Analyses concerned the proportional distribution of 12 pronoun types and linguistic contexts of increased use. Already at baseline, the AD-group produced a significantly higher proportion of D-pronouns (der, die, das, etc.) than the CTR-group. The increase in D-pronouns did not affect linguistic contexts favoring the use of personal pronouns. Instead, we found a significantly higher proportion of D-pronouns referring to family members and a significantly higher proportion of personal pronouns referring to non-family humans in the AD-group than in the CTR-group. Our results suggest that the predictive power of the use of pronouns can be significantly improved in computational modeling of the risk of AD by assessing language material that induces the use of pronouns in linguistic contexts affected by the increase.

Menopausal hormone therapy and risk of dementia: health insurance database in South Korea-based retrospective cohort study.

Menopausal hormone therapy (MHT) is used to alleviate the symptoms associated with menopause, despite the lack of recommendations for MHT in preventing dementia. Recent nationwide studies have explored the association between MHT and dementia risk, but the findings remain limited. This study aims to investigate the association between MHT and the incidence of Alzheimer's disease (AD) and non-AD dementia using national population data from Korea. We conducted a retrospective study using data from the National Health Insurance Service in Korea between January 1, 2002, and December 31, 2019. Women over 40 years were eligible for this study and classified into the MHT or non-MHT groups. The MHT group consisted of women who used Tibolone (TIB), combined estrogen plus progestin by the manufacturer (CEPM), estrogen, combined estrogen plus progestin by a physician (CEPP), and transdermal estrogen during menopause. We compared the risk of dementia between the MHT and non-MHT groups. The study included 1,399,256 patients, of whom 387,477 were in the MHT group, and 1,011,779 were in the non-MHT group. The median duration of MHT was 23 months (range: 10-55 months). After adjusting for available confounders, we found that different types of MHT had varying effects on the occurrence of dementia. TIB (HR 1.041, 95% confidence interval (CI) 1.01-1.072) and oral estrogen alone (HR 1.081, 95% CI 1.03-1.134) were associated with a higher risk of AD dementia. In contrast, there was no difference in the risk of AD dementia by CEPM (HR 0.975, 95% CI 0.93-1.019), CEPP (HR 1.131, 95% CI 0.997-1.283), and transdermal estrogen (HR 0.989, 95% CI 0.757-1.292) use. The use of TIB, CEPM, and oral estrogen alone increased the risk of non-AD dementia (HR 1.335, 95% CI 1.303-1.368; HR 1.25, 95% CI 1.21-1.292; and HR 1.128, 95% CI 1.079-1.179; respectively), but there was no risk of non-AD dementia in the other MHT groups (CEPP and topical estrogen). Our findings indicate that MHT has varying effects on the incidence of AD and non-AD dementia. Specifically, TIB, CEPM, and oral estrogen alone increase the risk of non-AD dementia, while transdermal estrogen is not associated with dementia risk. It is essential to consider the type of MHT used when assessing the risk of dementia in women.

A 6-items Questionnaire (6-QMD) captures a Mediterranean like dietary pattern and is associated with memory performance and hippocampal volume in elderly and persons at risk for Alzheimer’s disease

BACKGROUND: There is evidence that adherence to Mediterranean-like diet reduces cognitive decline and brain atrophy in Alzheimer's disease (AD). However, lengthy dietary assessments, such as food frequency questionnaires (FFQs), discourage more frequent use. OBJECTIVE: Here we aimed to validate a 6-items short questionnaire for a Mediterranean-like diet (6-QMD) and explore its associations with memory performance and hippocampal atrophy in healthy elders and individuals at risk for AD. METHODS: We analyzed 938 participants (N = 234 healthy controls and N = 704 participants with an increased AD risk) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). The 6-QMD was validated against the Mediterranean Diet (MeDi) score and the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) score, both derived from a detailed FFQ. Furthermore, associations between the 6-QMD and memory function as well as hippocampal atrophy were evaluated using linear regressions. RESULTS: The 6-QMD was moderately associated with the FFQ-derived MeDi adherence score (ρ = 0.25, p &lt; 0.001) and the MIND score (ρ = 0.37, p= &lt; 0.001). Higher fish and olive oil consumption and lower meat and sausage consumption showed significant associations in a linear regression, adjusted for diagnosis, age, sex and education, with memory function (β = 0.1, p = 0.008) and bilateral hippocampal volumes (left: β = 0.15, p &lt; 0.001); (right: β = 0.18, p &lt; 0.001)). CONCLUSIONS: The 6-QMD is a useful and valid brief tool to assess the adherence to MeDi and MIND diets, capturing associations with memory function and brain atrophy in healthy elders and individuals at increased AD dementia risk, making it a valid alternative in settings with time constraints.

Exploring the Effects of a Mediterranean Diet and Weight Loss on the Gut Microbiome and Cognitive Performance in Older, African American Obese Adults: A Post Hoc Analysis.

African American adults have a higher prevalence of Alzheimer's dementia (AD) than non-Hispanic Whites. The impact of a Mediterranean Diet (Med Diet) and intentional weight loss (IWL) on the gut microbiome may alter AD risk. A post hoc analysis of the Building Research in Diet and Cognition (BRIDGE) trial was performed to determine whether participation in an 8-month Med Diet lifestyle intervention with (n = 35) or without IWL (n = 31) was associated with changes in gut microbiota structure, abundance, and function and whether these changes were related to changes in cognitive performance. The results showed that family and genus alpha diversity increased significantly in both groups combined (p = 0.0075 and p = 0.024, respectively). However, there were no other significant microbially related within- or between-group changes over time. Also, an increase in Med Diet adherence was significantly associated with a decrease in alpha diversity at the phylum level only (p = 0.049). Increasing alpha diversity was associated with decreasing cognitive performance, but this association was attenuated after controlling for Med Diet adherence. In sum, an 8-month Med Diet lifestyle intervention with or without IWL did not appreciably alter the gut microbiome.

P29-035-23 The Association of Egg Consumption With Alzheimer's Dementia Risk - The Rush Memory and Aging Project

P29-035-23 The Association of Egg Consumption With Alzheimer's Dementia Risk - The Rush Memory and Aging Project

P29-022-23 The Association Between Dietary Choline Intake and Alzheimer's Dementia Risk: The Rush Memory and Aging Project

P29-022-23 The Association Between Dietary Choline Intake and Alzheimer's Dementia Risk: The Rush Memory and Aging Project

Genetic risk scores enhance the diagnostic value of plasma biomarkers of brain amyloidosis.

Blood-based biomarkers offer strong potential to revolutionize diagnosis, trial enrolment and treatment monitoring in Alzheimer's disease (AD). However, further advances are needed before these biomarkers can achieve wider deployment beyond selective research studies and specialty memory clinics, including the development of frameworks for optimal interpretation of biomarker profiles. We hypothesized that integrating Alzheimer's disease genetic risk score (AD-GRS) data would enhance the diagnostic value of plasma AD biomarkers by better capturing extant disease heterogeneity. Analysing 962 individuals from a population-based sample, we observed that an AD-GRS was independently associated with amyloid PET levels (an early marker of AD pathophysiology) over and above APOE ε4 or plasma p-tau181, amyloid-β42/40, glial fibrillary acidic protein or neurofilament light chain. Among individuals with a high or moderately high plasma p-tau181, integrating AD-GRS data significantly improved classification accuracy of amyloid PET positivity, including the finding that the combination of a high AD-GRS and high plasma p-tau181 outperformed p-tau181 alone in classifying amyloid PET positivity (88% versus 68%; P = 0.001). A machine learning approach incorporating plasma biomarkers, demographics and the AD-GRS was highly accurate in predicting amyloid PET levels (90% training set; 89% test set) and Shapley value analyses (an explainer method based in cooperative game theory) indicated that the AD-GRS and plasma biomarkers had differential importance in explaining amyloid deposition across individuals. Polygenic risk for AD dementia appears to account for a unique portion of disease heterogeneity, which could non-invasively enhance the interpretation of blood-based AD biomarker profiles in the population.

MBI‐apathy, ApoEɛ2, and risk for Alzheimer disease dementia

AbstractBackgroundApathy, characterized by decreased interest, initiative, and emotional reactivity, is amongst the most common neuropsychiatric symptoms in dementia. However, apathy can emerge before dementia and constitutes a domain of mild behavioral impairment (MBI), an at‐risk state for incident cognitive decline and dementia. MBI‐apathy is the de novo emergence of persistent apathy in dementia‐free older adults and may be a driving factor in dementia risk conferred by MBI. Apolipoprotein E (ApoE) is a risk marker for Alzheimer disease (AD) dementia. Compared to ApoEɛ3 homozygotes, ApoEɛ2 carriers are 40% less likely to develop AD while ApoEɛ4 carriers are 3.2‐14.9 times more likely. We investigated the association between MBI‐apathy, ApoE, and incident dementia. We hypothesized that ɛ2 would have protective effects for MBI‐apathy associated risk, compared to ɛ3 and ɛ4.MethodDementia‐free participants in the National Alzheimer’s Coordinating Centre were stratified as MBI‐apathy and no‐NPS until dementia diagnosis, based on Neuropsychiatric Inventory Questionnaire scores at 2 consecutive visits. ApoE genotypes were categorized by ɛ2 (ɛ2/ɛ2, ɛ2/ɛ3), ɛ3 (ɛ3/ɛ3), and ɛ4 (ɛ4/ɛ3, ɛ4/ɛ4) alleles. Group characteristics were contrasted to determine covariate inclusion in regression modelling. Cox regressions assessed risk of incident dementia and included an interaction term for MBI‐apathy and ApoE allele.ResultsOf the 3,644 participants (3,022 Normal‐Cognition); 314 had MBI‐apathy (Table 1). Significant main effects were found for MBI‐apathy and incident dementia (HR:2.51, 95% CI:1.99‐3.17, p&lt;0.001) as well as interaction effects with ApoE. In MBI‐apathy (ɛ3 as reference), the ɛ2 group had a 60% lower dementia risk (adjusted HR:0.40, 95% CI:0.19‐0.85) while ɛ4 had a 16% higher risk (adjusted HR:1.16, 95% CI:0.80‐1.69) (Figure 1). Of the 125 participants with apathy who progressed to dementia, 80.8% had AD. In the no‐NPS group (ɛ3 as reference), ɛ2 individuals had a 17% lower dementia risk (adjusted HR:0.83, 95% CI:0.52‐1.33) while ɛ4 individuals had a 177% higher risk (adjusted HR:2.77, 95% CI:2.13‐3.59) (Figure 2).ConclusionTo our knowledge, this is the first study examining the relationship between MBI‐apathy and ApoE status in determining dementia risk. Results suggest that ApoE modifies the association between MBI‐apathy and incident dementia with the ɛ2 allele acting as a protective factor.

Externalizing traits: Shared causalities for COVID-19 and Alzheimer's dementia using Mendelian randomization analysis.

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance-weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio [OR] = 1.456, 95% confidence interval [95% CI] = 1.224-1.731), hospitalized COVID-19 (OR = 1.970, 95% CI = 1.374-2.826), and AD (OR = 1.077, 95% CI = 1.037-1.119). The results were consistent using weighted median (WM), penalized weighted median (PWM), MR-robust adjusted profile score (MR-RAPS), and leave-one-out sensitivity analyses. Our findings assist in exploring the causal effect of externalizing traits on the pathophysiology of infection and severe infection of COVID-19 and AD. Furthermore, our study provides evidence that shared externalizing traits underpin the two diseases.

Association between migraine and Alzheimer's disease: a nationwide cohort study.

Migraine is a common chronic neurological disease characterized by pulsating headaches, photophobia, phonophobia, nausea, and vomiting. The prevalence of dementia in individuals aged over 65 years in Korea is more than 10%, and Alzheimer's disease (AD) dementia accounts for most cases. Although these two neurological diseases account for a large portion of the medical burden in Korea, few studies have examined the relationship between the two diseases. Therefore, this study investigated the incidence and risk of AD in patients with migraines. We retrospectively collected nationwide data from a national health insurance claims database governed by Korea's National Health Insurance Service. Among Koreans in the 2009 record, patients with migraine were identified according to the International Classification of Diseases, 10th revision (ICD-10) code G43. First, we screened the database for participants aged over 40 years. Individuals diagnosed with migraine at least twice over more than 3 months in a year were considered to have chronic migraine in this study. Further, all participants with an AD diagnosis (ICD-10 code: Alzheimer's disease F00, G30) were investigated for AD dementia development. The primary endpoint was AD development. The overall incidence of AD dementia was higher in individuals with a history of migraine than in those with no migraine history (8.0 per 1,000 person-years vs. 4.1 per 1,000 person-years). The risk of AD dementia was higher in individuals diagnosed with migraine (hazard ratio = 1.37 [95% confidence interval, 1.35-1.39]) than in the control group after adjustments for age and sex. Individuals with chronic migraine had a higher incidence of AD dementia than those with episodic migraine. Younger age (<65 years old) was associated with an increased risk of AD dementia compared to older age (≥65 years old). Higher body mass index (BMI) (≥25 kg/m2) was also associated with an increased risk of AD dementia compared to lower BMI (<25 kg/m2) (p < 0.001). Our results suggest that individuals with a migraine history are more susceptible to AD than those without a migraine history. Additionally, these associations were more significant in younger and obese individuals with migraine than in individuals without migraine.