bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intergenerational educational attainment and risk for incident dementia: The Atherosclerosis Risk in Communities [ARIC] Neurocognitive Study
Authors: Gupta Soumya , Morrill Valerie , Groechel Renée C. , Kucharska‐Newton Anna M. , Mosley Thomas H. , Lutsey Pamela L. , Meza Erika , Gottesman Rebecca F. 
Published: January 2025

AbstractBackgroundIndividuals with higher educational attainment have a lower risk for dementia, but it is less clear how educational attainment of an individual’s parents may influence dementia risk, particularly in diverse populations. The study goal was to investigate the association between intergenerational educational attainment for two adjacent generations (individuals and their parents) and the risk of incident dementia, in a community‐based study.MethodParticipants from the Atherosclerosis Risk in Communities (ARIC) study, a prospective community‐based cohort, were asked their own educational level (at study baseline; 1987‐1989; ages 44‐66 years) and that of each of their parents several years later. Dementia status was ascertained from baseline through 2020 using expert committee diagnoses from comprehensive neuropsychological assessments, informant interviews, telephonic assessments, hospitalization codes, and death certificates. Participants without dementia at baseline, and with non‐missing covariates and educational history were included. Educational level was classified (for participants and the higher‐educated parent) as less than high school (<HS); high school or GED (HS); and more than high school (>HS). We defined “overachievement” as a participant having higher educational attainment than their parent. Cox‐proportional hazard models were used to evaluate the association between intergenerational educational attainment and incident dementia risk.ResultAmong 10,626 participants (21.8% Black; 56.0% female) the overall dementia incidence rate was 7.9 [95% CI, 7.6‐8.3] per 1000 person‐years, with differences by educational category (Figure 1; log‐rank p<0.0001). High parental education level (>HS: HR, 0.88; 95% CI, 0.80‐0.99) and individual education level (>HS: HR, 0.62; 95% CI, 0.55‐0.70) were each significantly and independently associated with a lower risk of dementia (Table 1). Additionally, among participants whose parents had <HS education, overachieving parental education (i.e. participant has completed HS (HR, 0.69; 95% CI, 0.60‐0.79) or completed >HS (HR, 0.65; 95% CI, 0.56‐0.75)), as compared to matching parental education, was significantly associated with lower dementia risk (Table 2).ConclusionIndividuals with parents of higher educational attainment exhibit a reduced risk of dementia, and higher individual educational level is associated with reduced dementia risk, independent of parental education. Moreover, surpassing parental educational attainment, rather than matching it, is associated with a reduced risk of dementia.
Harmony of Mind and Motion: Exploring the Interplay between Physical Activity and Mild Behavioral Impairment in Dementia‐Free Older Adults
Authors: Mudalige Dinithi M , Guan Dylan X. , Smith Eric E. , Ismail Zahinoor 
Published: January 2025

AbstractBackgroundWhile dementia typically presents in later life, early‐to‐mid‐life factors like physical inactivity contribute to dementia risk. Mild Behavioral Impairment (MBI), marked by emergent and persistent behavioral changes in older adults, also contributes to dementia risk. However, there is limited research on the impact of physical activity in those with MBI. In a community‐dwelling sample of dementia‐free older adults, we determined the association between the total weekly frequency of engaging in physical activity and MBI severity and whether this association depended on the total duration of physical activity.MethodsData were obtained from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN‐PROTECT) study. Measures included the MBI Checklist (MBI‐C) and physical activity questions from the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Four physical activity domains were established (physical labor, cardiovascular activities, mind‐body exercises, and strength training). Multivariable negative binomial regression models modeled associations between MBI and weekly frequency of engaging in total and domain‐specific physical activity. All models were adjusted for age, sex, years of education, marital status, ethnocultural origin, and occupation type. Duration engaging in physical activity was explored as a covariate and a moderator.ResultsFor every 1 standard deviation (SD) increase in the total physical activity frequency was associated with a 18.3% (95%CI: ‐31.3—6.6, p = 0.002) lower MBI‐C total score. This association was moderated by total duration engaging in physical activity (expB = 1.0, 95%CI: 1.0‐1.0, p = 0.008), where the strength of the association weakened as the duration of physical activity increased. Additionally, every 1 SD increase in cardiovascular activity frequency and mind‐body activity frequency were associated with 18.1% (95%CI:‐30.9—6.5, p = 0.003) and 15.7% (95%CI:‐28.9—3.7, p = 0.006) lower MBI‐C total scores.ConclusionsMore frequent weekly physical activity and cardiovascular and mind‐body exercise were associated with lower MBI severity. As the duration of physical activity increased, the impact of the frequency of physical activity on MBI severity decreased, and vice versa. Since lower MBI scores are associated with a lower risk for dementia, these results might inform dementia risk reduction, even in those with few cognitive symptoms.
Specific plasma proteins and metabolites convey the effects of lifestyle interventions that improve cognition and function in Alzheimer’s disease
Authors: Roach Jared C. , Funk Cory C , Glusman Gwênlyn , Merrill David A. , Hodes John F. , Rapozo Molly K. , Edens Lance , Vaidyaraman Ananya , Shankle William R , Hood Leroy , Bramen Jennifer E. ,   the COCOA Consortium
Published: January 2025

AbstractBackgroundThe Coaching for Cognition in Alzheimer’s (COCOA) Trial was a prospective RCT testing a remotely coached multimodal lifestyle intervention for participants early on the Alzheimer’s disease spectrum. Intervention focused on diet, exercise, cognitive training, sleep, stress, and social engagement. Enrollment criteria targeted individuals with cognitive decline who were able to engage remotely with a professional coach. COCOA demonstrated cognitive and functional benefits. Dense omics data were collected on 53 individuals (≥ 58 years).MethodsWe sought to identify blood analytes that mediated the effects of specific elements of the multimodal intervention on specific outcomes. Outcomes were assessed with the MCI Screen (MCIS) and the Functional Assessment Staging Tool (FAST). We combined these and other measures with proteomics and metabolomics data. We analyzed the resulting dataset of over 300,000 distinct molecular data points—reflecting over 1400 measures— assayed over a period of two years. We used MEGENA to hierarchically multiscale cluster analytes based on correlated responses and identified individual metabolites and functional clusters associated with each intervention and outcome. We analyzed individual time courses of key analyte mediators to illustrate personalized effects of interventions and individualized functional and cognitive outcomes.ResultsDistinct sets of correlated serum analytes (“communities”) convey effects to functional (FAST) outcome and to cognitive (MCIS) outcome. Distinct communities respond to different modalities of intervention. Participants followed different aspects of the multimodal recommendations to different extents, and the analytes in their blood also responded idiosyncratically; analyte trajectories in different individuals show distinct dynamics. We made personalized predictions of future inflections in outcome based on observed changes in key serum mediators. We validated results with data from the Precision Recommendations for Environmental Variables, Exercise, Nutrition and Training Interventions to Optimize Neurocognition (PREVENTION) Trial.ConclusionsLifestyle interventions have profound effects on blood metabolites (Figure 1). These in turn convey subtler specific effects to cognition and broad‐based effects to function. Pathways that ameliorate the impact of AD via lifestyle interventions in some individuals include nitrogen subsystems, kidney function, and mitochondrial metabolism. These highlight the importance of clinical attention to overall health spanning multiple organ systems in individuals across the Alzheimer’s disease spectrum.
Lecanemab Slows Tau PET Accumulation
Authors: Charil Arnaud , Cao Youfang , Willis Brian A. , Hersch Steven , Irizarry Michael C. , Reyderman Larisa 
Published: January 2025

AbstractBackgroundLecanemab is an approved anti‐amyloid monoclonal antibody that binds with highest affinity to soluble Aβ protofibrils, which are more toxic than monomers or insoluble fibrils/plaque. In clinical studies, biweekly lecanemab treatment demonstrated a slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer’s disease (AD). Herein, we describe the impact of lecanemab treatment on tau PET.MethodChanges over time in tau PET SUVR ([18F]MK6240) were compared between placebo and lecanemab‐treated groups. Associations between baseline and change from baseline (CFB) in tau PET SUVR across brain regions were investigated. A quantitative systems pharmacology (QSP) model was developed to describe the dynamics of medial temporal (MTL) tau PET based on AD pathophysiology with three interlinked modules: Aβ pathway, tau pathway, and cognitive function. MTL tau PET data from the lecanemab Clarity AD study and other biomarkers from Clarity AD and lecanemab Study 201, and Alzheimer’s Disease Neuroimaging Initiative (ADNI), were used to inform and validate the model. QSP model‐based simulations were conducted to investigate the effect of lecanemab treatment on tau pathology.ResultHigher baseline tau levels were associated with higher tau accumulation across brain regions with disease progression. Lecanemab treatment significantly slowed accumulation of tau in temporal regions relative to placebo and disrupted association between baseline tau and CFB in tau across brain regions. QSP simulations predicted MTL tau PET accumulates 0.064 SUVR/year in placebo, and 0.092 SUVR/year in high baseline tau group (tau PET SUVR>1.5). QSP simulations predicted that lecanemab treatment halted tau PET accumulation in MTL region over 18 months of treatment and maintained suppression with continued biweekly lecanemab regardless of baseline tau levels.ConclusionLecanemab treatment demonstrated an impact on tau accumulation across brain regions. QSP model adequately described MTL tau PET for placebo and lecanemab across 30 months of Clarity AD data. QSP simulations suggest that lecanemab halts tau PET accumulation by clearing major tau pathology drivers of amyloid protofibril and plaque, slowing down long‐term cognitive decline. Taken together, tau PET data and QSP modeling support additional benefits of continued lecanemab treatment.
Long‐Term Effects of Lecanemab on Biomarkers of Neurodegeneration in Plasma
Authors: Teunissen Charlotte , Willis Brian A. , Bhagunde Pratik , Bell Robert , Penner Natasha , Sachdev Pallavi , Reyderman Larisa 
Published: January 2025

AbstractBackgroundLecanemab, a novel humanized immunoglobulin G1 monoclonal antibody targeting both neurotoxic Aβ protofibrils and Aβ plaques, has demonstrated the ability to substantially reduce markers of amyloid and significantly slow clinical decline on multiple measures of cognition and function in early AD in phase 2 (Study 201) and phase 3 (Clarity AD) studies. In these clinical studies, several plasma biomarkers assessments (Aβ42/40 ratio, p‐tau181, GFAP, and p‐tau217) showed improvements comparing lecanemab with placebo. Herein, we utilized modelling and simulations to evaluate the long‐term effects of lecanemab on biomarkers of neurodegeneration in plasma.MethodModels describing the relationship between serum lecanemab exposure and change in plasma biomarkers were developed using data pooled from lecanemab phase 2 and 3 studies. Individual serum lecanemab exposure was estimated using a population pharmacokinetic model and correlated with plasma biomarker concentrations using indirect response models. Simulations were conducted to evaluate the effect of lecanemab (10 mg/kg IV every 2 weeks) after 4 years of continuous treatment, discontinuation after 18 months of treatment, or transitioning to less frequent dosing at 18, 24, or 30 months.ResultData were available for up to 48 months continuous lecanemab treatment (Clarity AD) or 18 months continuous treatment, followed by a pause in dosing (average 24 months, range 5‐59 months) followed by a resumption of dosing (Study 201). All models were well parameterized and adequately described the data. Simulations demonstrated that biomarkers reverted towards pre‐treatment baseline after cessation of lecanemab treatment, with an average half‐life of approximately 1‐1.5 years. Transitioning to less frequent monthly dosing was sufficient to stabilize plasma biomarker concentrations at levels consistent with lecanemab efficacy.ConclusionModels describing the change in plasma biomarker levels over time in response to lecanemab treatment have been developed. Simulations conducted with these models demonstrate that continued treatment with lecanemab is required to sustain the benefit of lecanemab on amyloid and neurodegenerative pathology, but that less intensive dosing regimens are sufficient to maintain the changes in plasma biomarker levels consistent with lecanemab efficacy.
Association between number of teeth and cognitive decline: a systematic review and meta‐analysis of more than 4 million people
Authors: Chambergo‐Michilot Diego , Montesinos Rosa , Custodio Belen , Rivera Eva Arias , Butler Christopher , Custodio Nilton 
Published: January 2025

AbstractBackgroundDementia has sparked interest in identifying modifiable risk factors. It has been proposed that the number of teeth could play a crucial role in cognitive decline, suggesting possible mechanisms such as nutritional influence, inflammation, and neuronal feedback.MethodsWe performed a systematic literature search in January 2024 in PubMed, Scopus and Embase to search observational studies that reported the association between number of teeth and dementia or cognitive decline. We pooled the reported or calculated odds ratios in forest plots.ResultsWe included nine studies in our systematic review. The total sample size was 4022654 patients. There was one study with more than 4 million people. Three studies reported the independent variable (number of present teeth) as a continuous variable, and six studies reported it as a categorical variable. Three studies reported the reference category as ≥ 20 present teeth, and the remaining three studies reported the reference category as ≥ 22 present teeth. The most common tool to define cognitive decline was the Mini‐Mental State Examination. We did not find a significant association between number of teeth as a continuous variable and dementia or cognitive decline (OR: 1.00, 95% CI: 0.70‐1.44) (Figure 1). Regarding the 3 studies with reference category ≥ 22 present teeth, having 11‐21 present teeth was not significantly associated with dementia or cognitive decline (OR: 2.61; 95% CI: 0.61‐11.06) (Figure 2), in contrast to people with 0‐10 present teeth where it was significantly associated with dementia or cognitive decline (OR: 14.58; 95% CI: 3.52‐60.40) (Figure 3). Additionally, the other 3 studies with reference category ≥ 20 present teeth, having 10‐19 present teeth was not significantly associated with dementia or cognitive decline (OR: 1.93; 95% CI: 0.87‐4.27) (Figure 4), however, having 1‐9 present teeth was significantly associated with dementia or cognitive decline (OR: 1.34; 95% CI: 1.32‐1.36) (Figure 5).ConclusionA low number of teeth is associated with cognitive decline. Patients with cognitive decline should have a periodontal disease screening.
Characterizing Exposure to Traffic‐Related Air Pollution in a Diverse Alzheimer’s Disease Research Center Cohort
Authors: Decarli Charles , Farias Sarah Tomaszewski , Tobias Michele , Harvey Danielle J. , Carney Randy , Wexler Anthony , Bein Keith , Kleeman Mike , Lein Pamela , Meyer Oanh L. 
Published: January 2025

AbstractBackgroundMost studies on the associations between traffic related air pollution (TRAP), cognition, and dementia focus on particulate matter (PM) 2.5, are cross‐sectional and based on non‐Hispanic White (NHW) individuals. Less is known about how exposure to ultrafine PM (UFPM) affects cognition in racially/ethnically diverse cohorts. The UC Davis Alzheimer’s Disease Research Center (UCD ADRC) recently launched a study on TRAP that will assess the impact of UFPM on cognition, brain imaging and neuropathology. This abstract describes the broad geographic location, varying TRAP exposure, and demographic diversity of the cohort.MethodA total of 985 adults, average age of 81.3 ± 8.2 years, 62.6% female and consisting of 44% NHW, 24% Hispanic/Latino, 26.4% Black/African American, and approximately 4% other races/ethnicities had physical addresses geocoded to identify geographic coordinates; 29% of participants were cognitively normal, 18% had questionable cognitive impairment, 23% had mild cognitive impairment, and 30% had dementia. Detailed neuropsychological assessments and MRI were conducted annually along with collection of blood samples and data regarding social cultural variables. Median exposure of nearly 30 different TRAP measures including PM ranging in size from 0.1 to 10 µm measured over the years 2000‐2019 were calculated. Individual exposures were determined over an average of 4.4 ± 4.7 years of participant follow‐up.ResultParticipants lived in 28 counties throughout northern California with major clusters in the East Bay, Vallejo, Fairfield, Vacaville, Sacramento, and Central Valley south of Sacramento. We found highly significant differences in ethnoracial distribution according to county designation (Figure 1; p < 0.001; Fisher’s exact) and in both state and national Area Deprivation Index scores (ADI; Figure 2; p <0.0001, one‐way ANOVA). ADI varied significantly with ethnoracial background with Hispanic/Latino participants having the highest ADI at 29 ± 1. MANOVA analysis found significant (p <0.0001) geographic differences in 0.1 µm sized particles (e.g. Figure 3 for sodium and elemental carbon).ConclusionPreliminary analysis indicates significant differences in location, ethnoracial background, ADI, and TRAP exposure amongst UCD ADRC participants. This heterogeneity will allow comprehensive evaluation of the clinical impact of TRAP exposure on cognition among diverse individuals.
Effect of incident stroke on the risk of dementia over 10 years of follow‐up in a cohort of Asian American and White older adults in Northern California
Authors: Rojas‐Saunero L. Paloma , Zhou Yixuan , Hayes‐Larson Eleanor , Wu Yingyan , Nianogo Roch A , Whitmer Rachel A. , Gilsanz Paola , Elser Holly C , Mayeda Elizabeth Rose 
Published: January 2025

AbstractBackgroundAcute stroke may increase dementia risk. Previous work has not accounted for time‐varying covariates that could increase risk of stroke and dementia over time, and there has been very limited evidence on the effect in Asian Americans. We aimed to estimate the effect of incident stroke on dementia risk over 10 years of follow‐up among Asian American and White older adults in Northern California considering time‐varying covariates.MethodsWe included Chinese (n = 6034), Filipino (n = 4649), Japanese (n = 3099), and White (n = 133208) members of Kaiser Permanente who participated in the Research Program on Genes, Environment, and Health and the California Men’s Health Study surveys (2002‐2009), with linked electronic health records (EHR) data until 2020. Inclusion criteria included age 60‐89 years old and no history of stroke or dementia at the time of survey (baseline). Incident stroke (ischemic and hemorrhagic) and incident dementia diagnosis were defined based on ICD codes from EHR. To ensure comparability between those with and without incident stroke at all time points before incident stroke, we fit annual inverse probability treatment weights (IPTW) to adjust for confounding, including baseline sociodemographic covariates and time‐varying (annual) cardiovascular covariates. We also fit censoring weights (IPCW) so that those who remained alive over follow‐up are representative of those who died. We estimated the risk ratio (RR) and risk difference (RD) for incident stroke and subsequent dementia from weighted Kaplan‐Meier survival estimators at 10 years of follow‐up for each racial/ethnic group. Sensitivity analyses examined ischemic stroke as the outcome.ResultsThe cause‐specific cumulative incidence of stroke at 10 years of follow‐up ranged between 10.9% (95%CI: 10.0%, 11.8%) for Chinese and 14.1% (95%CI: 12.7%, 15.5%) for Japanese participants. After adjusting for confounding and censoring, the RR for the effect of incident stroke on subsequent dementia was 5.6 (95%CI: 4.2, 7.3) for Chinese, 3.8 (95%CI: 2.7, 5.1) for Filipino, 4.9 (95%CI: 3.0‐6.6) for Japanese participants, and 3.3 (95%CI: 3.1‐3.5) for White participants. Confidence intervals between groups mostly overlapped (Figure). Restricting analysis to ischemic stroke only yielded similar results.ConclusionThe effect of stroke on risk of dementia is large among Asian American and White older adults.