bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of recruitment incentives in early Alzheimer’s disease clinical trials
Authors: Ritchie Marina , Witbracht Megan G. , Russ Eunji , Sajjadi S. Ahmad , Thai Gaby , Tam Steven , Gillen Daniel L , Grill Joshua D 
Published: January 2025

AbstractBackgroundAmid recent approvals, early Alzheimer’s disease (AD) remains an active area of treatment development, but research on the utility of recruitment incentives in early AD trials remains limited. We examined how trial design features impact enrollment decisions among Mild Cognitive Impairment (MCI) patients and their family members.MethodWe performed a conjoint analysis experiment to compare early AD patients’ preferences for trial features. Individuals with MCI were asked to rate their willingness to participate in a series of trial scenarios (using a 7‐point ordered scale) that varied in four pre‐selected factors, each with two levels. Three trial incentives were included: 1) active‐control design with participants randomized to an investigational anti‐amyloid therapy or aducanumab (vs. placebo control), 2) tau PET disclosure (vs. no return of tau PET results), and 3) remote study partner participation (vs. required in‐person study partner participation). We included one negative control (5% vs. 25% risk of brain swelling). We used a generalized estimating equations (GEE) model to account for within‐subject correlation and to assess the utility of the differing factor levels. An exchangeable working correlation structure was used for parameter estimation, and robust variance estimates for model coefficient estimates were used for final inference.ResultAmong 26 patients with MCI (mean [SD] age 78.3 [8.2], 31% female, 85% non‐Hispanic White), returning tau PET results had the highest utility (est: 0.47; CI: 0.13, 0.81; p = 0.007). Trials with the option for remote study partner participation showed a similar trend in utility (est: 0.29; CI: ‐0.05, 0.63; p = 0.097). Trials with active‐controlled design (est: 0.01; CI: ‐0.33, 0.35; p = 0.956 did not demonstrate significant utility and trials with higher risk of brain swelling had a negative utility (est: ‐0.64; CI: ‐0.99, ‐0.30; p<0.001) (Figure 1).ConclusionThese findings suggest that returning biomarker results may have a greater impact on participant enrollment decisions than would use of active‐controlled designs or providing the option for study partners to participate remotely.
Association of Prenatal Pesticide Exposure with Plasma Aβ 42/40 Ratio in Midlife: Evidence from the Child Health and Development Studies
Authors: Richardson Jason R , Mhatre‐Winters Isha , Cirillo Piera , Krigbaum Nickilou , Factor‐Litvak Pam , Go Young‐Mi , Jones Dean P , Cohn Barbara 
Published: January 2025

AbstractBackgroundEnvironmental factors are increasingly being recognized as significant contributors to Alzheimer’s and Related Dementias (ADRD). Previously, we reported that higher serum concentrations of DDE, the highly persistent metabolite of the pesticide DDT was associated with increased risk of Alzheimer’s disease. We further demonstrated in cell and animal models that DDT and DDE increase amyloid pathology in the brain (Fig. 1). However, little is known about the effects of prenatal exposure on amyloid in humans.MethodOffspring born into the Child Health and Development Studies (CHDS) pregnancy cohort from 1960 ‐1963 in Oakland, CA were recruited for a diverse follow‐up study of health disparities in 2010. Participants completed cognitive function assessments, and provided interview data and blood samples, in their late 40’s to early 50’s. Aβ 42/40 was measured from the stored plasma taken in midlife using the Quanterix Neurology 3‐Plex A kit. Prenatal p, p’‐DDE, measured in archived maternal pregnancy serum, was available for this pilot sample, n = 160. Associations were estimated in linear, and binomial and multinomial logistic regression models, adjusted for race and sex.ResultHigher prenatal p, p‐DDE was associated with lower Aβ 42/40 in mid‐life (Fig. 2). In logistic models (Table 1), the Odds Ratio [OR] estimating lower Aβ 42/40 (tertiles 1 or 2 vs. tertile 3) = 2.6; 95% Confidence Limits [CL] = 1.0‐6.9 and OR = 3.2; 95% CL = 1.1‐9.8 for p, p‐DDE tertiles 2 and 3, respectively. Test of trend across p, p’‐DDE tertiles was significant (P‐value = 0.04). Associations were robust to multiple alternative modeling approaches (Table 1). Adjustment for achieved education in mid‐life did not alter results.ConclusionHigher prenatal exposure to DDE is associated with lower plasma Aβ 42/40 in midlife, a putative prodromal marker for ADRD. Identification of individuals or populations more highly exposed to DDT/DDE may determine those at increased risk for ADRD later in life and allow for early intervention and prevention from progression to ADRD.
Marital Status and living arrangements, Brain Reserve, and Cognitive Reserve Among Diverse Older Adults
Authors: Lee Ji Hyun , Scambray Kiana A. , Morris Emily P. , Sol Ketlyne , Palms Jordan D , Zaheed Afsara B , Manly Jennifer J. , Brickman Adam M. , Zahodne Laura B. 
Published: January 2025

AbstractBackgroundMarital status is an important but often overlooked sociodemographic factor that could shape cognitive health in late adulthood. Being married is shown to be linked to lower risk of dementia, but less is understood about underlying mechanisms contributing to this relationship, such as brain reserve (BR) and cognitive reserve (CR). Further, less is known about how living arrangement, independent of marital status, is associated with late‐life cognition. The current study examines (1) associations between marital status, BR, and CR among diverse older adults and (2) whether living arrangement is linked to BR and CR among unmarried adults.MethodCross‐sectional data come from the Washington Heights‐Inwood Columbia Aging Project (WHICAP; N = 778, 41% Hispanic, 33% non‐Hispanic Black, 25% non‐Hispanic White; 64% women). Self‐reported marital status was categorized as currently married, previously married (i.e., divorced, separated, widowed), and never married. Magnetic resonance imaging (MRI) markers of BR included regional cortical thickness (in Alzheimer’s disease signature regions), hippocampal volume, gray matter volume, and white matter hyperintensities. CR was defined as residual variance of an episodic memory composite after residualizing MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender. Age and education was controlled and physical health and income were explored as mediators.ResultMarital status was associated with CR, but not BR, among White and Hispanic subgroups, and among women, such that those who were previously married had lower CR than their married counterparts. Never married women also had lower CR than married women. Among men only, marital status was associated with BR, but not CR, such that previously married men had lower gray matter volume than married men; however, this finding was not independent of income. Among currently unmarried individuals, living with others was not associated with greater BR nor CR. All findings were independent of age, education, and physical health.ConclusionOur findings show differential links between marital status and reserve mechanisms across race and ethnicity and sex/gender, underscoring the importance of examining marital status in older adult’s brain health. Future studies should examine other mechanisms that link marital dissolution and lower CR and nuanced contexts of marital history.
The association between mid‐life personality traits and late‐life dementia risk in the Wisconsin Longitudinal Study
Authors: Strait Brittani J. , Trane Ralph , Lange Kate , Asthana Sanjay , Williams Victoria J. 
Published: January 2025

AbstractBackgroundPersonality traits, namely higher neuroticism and lower conscientiousness, are predictive of dementia, although the complex relationship has yet to be fully explained. With >60 years of prospectively collected data, the Wisconsin Longitudinal Study (WLS) provides a unique opportunity to thoroughly evaluate this association in a population‐based randomly selected cohort. Using a gold‐standard diagnostic approach to characterize dementia prevalence, we leverage life course WLS data to examine the association between mid‐life personality traits and late‐life dementia risk.MethodBig Five personality traits (neuroticism, conscientiousness, openness, extraversion, and agreeableness) were prospectively measured in 1993‐94 at mid‐life (ages 54‐55). Cognitive status was determined in late‐life starting in 2020 (age 81) using a two‐phased approach. Participants were first screened via the Telephone Interview for Cognitive Status (TICS‐m), with those scoring below cutoff (≤28) selected for additional comprehensive medical and cognitive assessment reviewed by a multi‐disciplinary clinician consensus panel to determine dementia diagnosis. To evaluate the association between midlife personality traits and late‐life all‐cause dementia risk, we performed a binary logistic regression controlling for age, sex, ApolipoproteinE‐4 (ApoE‐4) status, adolescent IQ, education, comprehensive smoking history, and lifetime burden of systemic health factors (hypertension, diabetes, stroke, heart disease).Result3765 WLS participants were included in analyses. The overall logistic regression model was statistically significant (Chi2(14) = 207.52, p<0.001), explaining 12.3% of the variance in dementia outcome. Each unit increase in mid‐life conscientiousness corresponded to a 4.5% decrease in the odds of late‐life dementia (OR = 0.955 [95% CI: 0.926‐0.985], p = 0.003), while the remaining four personality factors were not predictive of dementia risk.ConclusionUsing a longitudinal population‐based cohort, we find that lower mid‐life conscientiousness increases risk for dementia in late‐life, and conversely, higher mid‐life conscientiousness is protective for late‐life dementia. Although prior research suggests higher neuroticism is also associated with dementia outcomes, our data did not support this finding. Future work should explore potential pathways and mechanisms by which personality traits affect cognition and neurodegenerative disease risk, including the possible mediating role of personality‐associated health behaviors.
Glycoproteome‐wide analyses in the dorsolateral prefrontal cortex identified glycopeptiforms associated with cognitive decline in specific cognitive domains
Authors: Beeri Michal S , Levin Yishai , Morgenstern David , Tikotzki Nili , Levy Hila , Cooper Itzik , Klein Hans‐Ulrich , Bennett David A. , Yu Lei , Buchman Aron S 
Published: January 2025

AbstractBackgroundMolecular omics studies of aging brains have identified genes and proteins related to cognitive decline. Identifying proteins that are linked to specific cognitive abilities has potential to catalyze the development of targeted therapies for specific cognitive deficits. Posttranslational modifications of proteins with glycans modify protein function. Here, we identified glycopeptiforms associated with decline in specific cognitive domains.MethodWe studied brains of 366 older decedents from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) with annual cognitive testing, postmortem indices of ten AD/ADRD pathologies and proteome‐wide data, from dorsal lateral prefrontal cortex (DLPFC). We quantified 11,012 glycopeptiforms from DLPFC using liquid chromatography with tandem mass spectrometry, which is able to identify both glycated and glycosylated glycopeptiforms, two distinct molecular processes. We employed linear mixed‐effects models controlling for age, sex and education to identify glycopeptiforms associated with decline in five cognitive domains (episodic memory, semantic memory, working memory, perceptual speed and visuospatial abilities) correcting for multiple comparisons (p<5×10‐6). In further analyses, we adjusted for 10 neuropathologies and for the constituent proteins of the glycopeptiforms.ResultWe found eight glycated (Table 1) and eight glycosylated glycopeptiforms (Table 2) that were significantly associated with cognitive decline. Glycated glycopeptiformswere associated primarily with decline in working memory. In contrast, glycosylated glycopeptiforms were associated with all cognitive domains except for visuospatial abilities. Higher levels of glycated glycopeptiforms were always related to faster cognitive decline while higher levels of glycosylated glycopeptiforms were primarily associated with slower cognitive decline. Three glycopeptiforms identified weresituated on the protein neuronal pentraxin 2, linked to AD. The HexNAc(5)Hex(4)Fuc(2) glycan composition appeared in half of the significant glycosylated glycopeptiforms while only in <0.05% of the 11,000 glycopeptiforms, suggesting its specific involvement in cognition. Adjustment for 10 neuropathologies attenuated 3 of the 25 significant associations. Adjustment for the constituent proteins did not alter any of the results suggesting that the post‐translational modification itself may have a role in cognitive decline.ConclusionGlycopeptiforms in aging brains may contribute to decline in distinct cognitive abilities. Further drug discovery targeting these glycopeptiforms may lead to therapies that prevent specific cognitive deficits.
Examination of sleep metrics from spectral analysis, self‐report, and the Sleep Profiler to establish test‐retest reliability in an Alzheimer’s disease cohort
Authors: Pedersen Taylor J , McCullough Austin A. , Toedebusch Cristina D , Hess Ashley , Richardson Rachel , Morris John C. , Holtzman David M. , Gordon Brian A. , Lucey Brendan P 
Published: January 2025

AbstractBackgroundIt is thought that sleep plays a role in the development and course of Alzheimer’s disease (AD). There are numerous metrics and methods to gather sleep data including measures from self‐reports, actigraphy, or EEG. There has been limited research examining the reliability of these variables over time in healthy individuals as well as the optimal method to gathering such data. We sought out to determine which sleep metrics are the most reliable over a long timescale in a cohort of amyloid negative individuals.MethodSleep was assessed over six nights at home using three instruments simultaneously: single‐channel EEG (scEEG) (Sleep Profiler, Advanced Brain Monitoring, Carlsbad, CA), actigraphy (Actiwatch2, Philips Respironics, Andover, MA), and sleep diaries. Participants returned three years later for their second visit using the same sleep assessments. Longitudinal data was analyzed for 19 cognitively normal individuals (CDR = 0) who were amyloid negative by PET. To determine the most reliable method of gathering sleep data, we grouped the metrics into three categories: spectral analysis, self‐reports, and Sleep Profiler data. We then examined the intraclass correlation coefficient (ICC) between visits as a measure of reliability.ResultSpectral analysis demonstrated the highest test‐retest reliability (mean ICC = 0.798, min. ICC = 0.578, max. ICC = 0.877) followed by the sleep profiler data (mean ICC = 0.558, min. ICC = 0.405, max. = 0.932). Self‐report data exhibited the lowest test‐retest reliability (mean ICC = 0.485, min. ICC = 0.150, max. ICC = 0.729) (Fig. 1). In examining metrics with high ICC values from each category, individual slow wave activity (SWA) data remained highly consistent between visits (ICC = 0.874) (Fig. 2A). REM Latency was the strongest sleep profiler metric and had an ICC value of 0.862 (Fig. 2C). Within self‐report data, the daytime napping questionnaire had the highest test‐retest reliability (ICC = 0.729) (Fig. 2B).ConclusionSpectral analysis proved to be the most reliable metric in assessing sleep in amyloid‐negative individuals. Given their lower reliability the Sleep Profiler and self‐report questionnaires are likely not sufficient to evaluate sleep quality alone. Further analysis in amyloid‐positive individuals is being conducted.
The Long‐Term Effects of the Care Ecosystem Dementia Care Management Program on Quality of Life and Caregiver Well‐being
Authors: Possin Katherine L , Dulaney Sarah , Wood Andrew J , Bonasera Stephen , Allen Isabel Elaine , Sideman Alissa Bernstein , Kanzawa Mia , Merrilees Jennifer , Lee Kirby P , Chiong Winston , Braley Tamara , Hooper Sarah M , Gearhart Rosalie , Medsger Helen Bundy , Harrison Krista L , Hunt Lauren , Kiekhofer Rachel , Chow Chris , Miller Bruce L. , Guterman Elan L 
Published: January 2025

AbstractBackgroundDementia care management programs, including the Care Ecosystem, have been shown to improve patient and caregiver outcomes, reduce unnecessary healthcare expenditures, and are the focus of Medicare’s new GUIDE payment model. Until now, prior research has focused on evaluating the effectiveness of participating for a short (eg, 12‐month) time frame. The purpose of this study was to evaluate the effects of the Care Ecosystem when delivered for up to 5 years or end of life.MethodsOf the 804 PLWD‐caregiver dyads enrolled in the previously reported single‐blind 12‐month RCT of the Care Ecosystem (NCT02213458), 456 reported high baseline caregiver burden and were included in this extension trial (NCT04287738). Telephone‐based dementia care management was delivered by a trained care team navigator, with a team of dementia specialists. Primary outcome: PLWD quality of life (QoL‐AD); Secondary: caregiver depression (PHQ‐9), self‐efficacy (Care Ecosystem Self‐Efficacy scale), and burden (Zarit‐12), and PLWD ED and hospital use. The cumulative treatment effect was the sum of the average treatment effect on each outcome at each timepoint, weighted by the number of active participants over time. Linear mixed effects models were used to estimate the treatment effect at the annual timepoints. Caregivers’ perspectives on the value of longer care were derived via semi‐structured interviews after 5 years of participation.ResultsIn this prespecified analysis including 297 dyads randomized to Care Ecosystem participation and 159 dyads to usual care, the cumulative 5‐year treatment effect on quality of life, caregiver depression and self‐efficacy were significant; there was a trend for caregiver burden. These treatment effects were most robust during the first 2‐3 years of the study (Figure). The cumulative treatment effects on ED and hospital use were not significant. Most caregivers who participated for the 5 full years indicated that the emotional and practical support was helpful for the duration, but many derived the greatest benefit during the first few years when they were newer to being a caregiver.ConclusionThe benefits of dementia care management on PLWD quality of life and caregiver well‐being are sustained for five years, with the greatest effects in the first 2‐3 years.
Investigation of correlation between negative communication and characteristics of caregivers of people with dedmentia
Authors: da Silva Amanda Gorziza , Gheno Lucimara Lehmen , Fernandez Liana Lisboa , Rieder Carlos Roberto Mello , Beber Bárbara Costa 
Published: January 2025

AbstractBackgroundCaregivers of people with dementia (PwD), assuming the responsibility for another life, can become physically and emotionally overwhelmed, leading to increased psychiatric symptoms such as anxiety and depression. Similarly, the level of neuropsychiatric symptoms in PwD is associated with caregiver burden. Faced with this burden and the challenges of managing dementia, caregivers may potentially channel their feelings of frustration and exhaustion from caregiving into the way they communicate with the person with dementia. It is important to identify the determinants of negative communication by caregivers to develop educational programs to improve communication. The objective of this study was to verify the correlation between negative communication and characteristics of caregivers of PwD.MethodThis is an excerpt from a descriptive cross‐sectional observational study involving a sample of 11 caregivers. We collected sociodemographic data and information regarding the characteristics of care. The following tools were administered to caregivers of PwD: Negative Communication Scale (NCS), which assesses the caregiver’s negative communication through questions related to daily communication with the patient; Zarit Burden Scale, which assesses caregiver burden; Mini‐Mental State Examination (MMSE), a screening test for a quick evaluation of cognitive function. Statistical analyses were conducted using Chi‐Square and Spearman tests with a significance level of 5%.ResultThe study included 11 caregivers of PwD. Their characteristics are presented in Table 1. Table 2 shows the correlations between the NCS and characteristics of the sample. There was a positive correlation between the NCS and education, suggesting that the higher the education, the worse the perception of the caregivers regarding their use of negative communication. Despite the absence of statistical significance, there was a trend for positive correlations with MMSE and Zarit scores. Additionally, there was no significant difference in the NCS when compared between sexes (p = 0.57) and types of relationships of the caregivers with the PwD (p = 0.48) (Chi‐Square test).ConclusionEducation may be correlated with the occurrence or perception of negative communication acts used by caregivers. Despite the presented correlations, it is necessary to increase the sample size to demonstrate/confirm these correlations, as well as trends in correlations.