Risk Of Alzheimer's Disease Dementia Research Articles

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. ObjectiveTo 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 (FFQ). Participants’ first FFQ 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 levels 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 brian. 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] 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 = 0.53; 95% Confidence Interval: 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 39% of the total effect of egg intake on incident Alzheimer’s dementia were 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 the 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.

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.

Evaluating the association between genetically proxied ACE inhibition and dementias.

Angiotensin-converting enzyme (ACE) has been implicated in the metabolism of amyloid beta; however, the causal effect of ACE inhibition on risk of Alzheimer's disease (AD) dementia and other common dementias is largely unknown. We examined the causal association of genetically proxied ACE inhibition with four types of dementias using a two-sample Mendelian randomization (MR) approach. Genetically proxied ACE inhibition was associated with increased risk of AD dementia (odds ratio per one standard deviation reduction in serum ACE [95% confidence interval]; 1.07 [1.04-1.10], P=5×10-07 ) and frontotemporal dementia (1.16 [1.04-1.29], P=0.01) but not with Lewy body dementia or vascular dementia (P >0.05). These findings were independently replicated and remained consistent in sensitivity analyses. This comprehensive MR study provided genetic evidence for an association between ACE inhibition and the risk for AD and frontotemporal dementias. These results should encourage further studies of the neurocognitive effects of ACE inhibition. This study evaluated genetically proxied angiotensin-converting enzyme (ACE) inhibition association with dementias. The results suggest an association between ACE inhibition and Alzheimer's disease. The results suggest an association between ACE inhibition and frontotemporal dementia. Those associations can be interpreted as potentially causal.

Stress and the risk of Alzheimer dementia: Can deconstructed engrams be rebuilt?

The exact neuropathological mechanism by which the dementia process unfolds is under intense scrutiny. The disease affects about 38 million people worldwide, 70% of which are clinically diagnosed with Alzheimer's disease (AD). If the destruction of synapses essential for learning, planning and decision-making is part of the problem, must the restoration of previously lost synapses be part of the solution? It is plausible that neuronal capacity to restitute information corresponds with the adaptive capacity of its connectivity reserve. A challenge will be to promote the functional connectivity that can compensate for the lost one. This will require better clarification of the remodeling of functional connectivity during the progression of AD dementia and its reversal upon experimental treatment. A major difficulty is to promote the neural pathways that are atrophied in AD dementia while suppressing others that are bolstered. Therapeutic strategies should aim at scaling functional connectivity to a just balance between the atrophic and hypertrophic systems. However, the exact factors that can help reach this objective are still unclear. Similarities between the effects of chronic stress and some neuropathological mechanisms underlying AD dementia support the idea that common components deserve prime attention as therapeutic targets.

Association of impaired kidney function with dementia and brain pathologies: A community-based cohort study.

The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. A total of 1354 dementia- and kidney disease-free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2-9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow-up, 453 participants died and underwent autopsies for neuropathological assessment. Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio=1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

1173. Increased risk of dementia in patients after Scrub typhus: a nationwide, population-based study in Korea

Abstract Background Scrub typhus causes systemic vasculitis and can lead to complications ranging from pneumonia and acute renal injury to meningitis or encephalitis. In South Korea, it occurs not only in rural areas but also in urban areas, and especially high in older people. We hypothesized that patients with scrub typhus are predisposed to increased risks for developing dementia. Methods We performed a population-based cohort study, in which persons aged between 60∼89 years, used the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. The case definition of scrub typhus was based on the ICD-10 diagnostic code and prescription of doxycycline more than three days. Dementia was defined as patients with the code in expending benefit coverage or patients with the ICD-10 codes, examination codes and drug codes. The control group was selected as stratifying by age and gender at a ratio of 1:5 to the number of the case group in study population. Results During the observational periods, Of 76,073 patients had diagnosed with scrub typhus, 5,026 excluded due to diagnosed with scrub typhus during window period, with dementia or died before index date, 71,047 patients were included as case group. 355,235 patients were included as controls. During a mean follow-up of 5.6±2.9 years, 14,089 (19.8%) patients with previous scrub typhus and 61,807 (15.2%) controls had been developed dementia. Scrub typhus was significantly associated with dementia (adjusted hazard ratio [aHR], 1.12; 95% confidential interval [CI], 1.10-1.15, P&amp;lt; 0.001). Of dementia classification, the risk of Alzheimer dementia was significantly higher in the case group (17.8% vs 15.2%; aHR, 1.15; 95%CI, 1.13-1.18, p&amp;lt; 0.001), however, there was no significant difference in the risk of vascular dementia (2.1% vs 2.2%; aHR, 0.98; 95%CI, 0.83-1.16, p=0.82). Cumulative incidence of dementia during the follow-up period by the history of scrub typhus It shows in both groups dementia incidence increased over time and the case group had higher incident dementia compared with control group. Conclusion History of scrub typhus infection in elderly was associated with increased risk for dementia, especially Alzheimer’s dementia. Our results suggest that prevent measures of dementia could be improved by preventing and treating scrub typhus. Disclosures All Authors: No reported disclosures.

Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes

Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid β deposition (Aβ). A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aβ deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.