bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially modifiable factors explaining monozygotic twin discordance in amyloid pathology
Authors: Konijnenberg Elles , Coomans Emma M. , Tomassen Jori , Kate Mara Ten , Landen Sophie M. , Heuvelink Joost , Collij Lyduine E. , Tijms Betty M. , Teunissen Charlotte E. , Barkhof Frederik , van Berckel Bart N.M. , Scheltens Philip , Boomsma Dorret I , de Geus Eco J.C. , Visser Pieter Jelle , Braber Anouk 
Published: December 2023

AbstractBackgroundThe heritability of global amyloid burden in older adults was previously found to be moderate (41%), suggesting environmental factors to play an important role in early Alzheimer’s disease (AD) pathology. Identifying these factors may aid in the development of successful prevention strategies. Several, potentially modifiable, risk factors for dementia have been previously reported by Livingston and colleagues (Lancet, 2020). We here aim to identify which of these risk factors explain observed twin discordance in amyloid pathology in a sample of cognitively unimpaired monozygotic twin‐pairs.MethodsWe included 31 initially cognitively unimpaired twin‐pairs aged>60 years from the EMIF‐AD PreclinAD study who were discordant on amyloid status (defined by visual read of dynamic [18F]flutemetamol‐PET images). Paired samples t‐tests (continuous measures) and McNemar’s tests (dichotomous measures) were applied to investigate which factors associated with twin discordance. Selected risk factors included comorbid diseases, lifestyle and vascular risk factors (see table 2).ResultsTwins were on average 72.7±7.0 years old, consisted of 48% females, and 58% Apoe‐ε4 carriers (table 1). Twins with a positive amyloid status showed lower body mass index (BMI) and glucose levels compared to their amyloid negative co‐twin (table 2, figure 1A&B). We also observed a trend towards lower diastolic blood pressure in amyloid positive twins (table 2). In accordance with inclusion criteria for the study we observed very low prevalence of comorbid disorders in both groups. Further, no group differences were observed in lifestyle factors, such as smoking, alcohol use, physical activity and sleep quality.ConclusionsIn a sample of monozygotic twin‐pairs discordant for amyloid pathology, we found lower BMI and glucose levels to be associated with the presence of amyloid pathology. Although Livingston and colleagues reported high BMI (obesity) at mid‐life (age 45‐65) to increase the risk for dementia, effects of BMI have previously been found to differ in mid‐ and late‐age populations. In line with our results, lower BMI at later life (>65 years) has previously been found to increase AD‐risk. For the development of prevention strategies, it would be of relevance to further investigate these dynamic age‐related effects.
Team‐Based Learning Approach to Practice Improvements in a Memory Clinic
Authors: Love Marissa C. Natelson , Pilonieta Giovanna , Geldmacher David S. 
Published: December 2023

AbstractBackgroundWorkface projections indicate an increasing shortfall in neurologists and other medical specialists to treat persons with Alzheimer’s disease and other causes of dementia (Dall et al. Neurology 2013). This problem will be further magnified by available disease modifying therapies aimed at earlier stages of illness, markedly expanding the patient pool (Anderson et al. J Prev Alzheimers 2022; Hlavka et al. Rand 2019). With the Alzheimer’s disease treatment landscape approaching these turning points the University of Alabama at Birmingham Brain Aging and Memory (BAM) Clinic undertook a multidisciplinary expansion to improve access and increase the role of nonphysician professionals to optimize care. Onboarding this interdisciplinary team was complicated by separation of staff members mandated by the COVID‐19 pandemic. These factors, along with emerging use of “team‐based learning” educational models led to the creation of the BAM Learning Club (BAM LC).MethodsBAM LC is a weekly synchronous online series of didactics, lectures, case discussions, journal reviews, and team‐building wellness activities. Participants include Neurologists, Psychiatrists, Psychologists, RN Case managers, RN Clinical Care Coordinators, Social Workers, Nurse Practitioners, Pharmacists, Caregiver Counselors, Research Scientists, Clinical Trial Coordinators, Postdoctoral Fellows, Residents, and Medical Students. Sessions are recorded for future onboarding and educational needs. Content is generated by the BAM LC members with support from its director.ResultsBAM LC began in June 2021 and has continued weekly with increasing interest and attendance. Shared learning has led to practice improvements, a collaborative environment, and a cohesive multidisciplinary team. Recorded sessions have been used to provide education outside of our cohort and will be maintained for future use.ConclusionTeam‐based learning has resulted in better academic, clinical, and communication outcomes among health care professionals (Joshi et al. Cureus 2022). Multidisciplinary team‐led learning opportunities focused on dementia care could serve as a tool to promote further practice improvement, collaboration, and cohesion within healthcare organizations. Normalization of synchronous remote learning during the pandemic facilitated acceptance, uptake, and participation across disciplines. This process also has the potential to provide further system‐wide education in health systems to diversify the workforce and improve readiness to treat a rapidly expanding patient population.
Characterize demographics, comorbidities and co‐medications in newly diagnosed United States (US) Alzheimer’s Disease patients using Medicare claims
Authors: Schroeder Krista Marie , Afonso Ana Sofia , Wang Huabo , Grace Sarah , Phipps Adam , Sims John R. 
Published: December 2023

AbstractBackgroundAccess to Medicare claims provides a unique opportunity to broadly characterize diseases affecting US adults 65+ years of age. This can provide insights into real world populations and a basis of comparison to those in clinical trial populations. To this end, this study characterizes demographics, comorbidities and co‐medications in patients newly diagnosed with Alzheimer’s Disease (AD).MethodsThis study utilized Medicare Part A and B claims (Fee‐For‐Service and Medicare Advantage) limited to patients with at least one 2019 medical encounter. The study’s source population was limited to those 65+ years of age with Medicare Part D coverage and 1‐year pre‐encounter continuous enrollment. From this source population, three newly diagnosed AD cohorts were compiled; cohort 1 utilized the 1‐year Bynum‐Standard Alzheimer’s disease and related dementia (ADRD) claims algorithm, cohort 2 adapted the ADRD algorithm to include only specific AD diagnoses, and cohort 3 was selected based on new use of cholinesterase inhibitors (irrespective of ADRD diagnosis). Demographics, comorbidities, and co‐medications present in the 1‐year pre‐cohort qualification are described.ResultsFrom 53,890,958 patients with at least one 2019 medical encounter, 33,315,038 qualified for the source population. Of these patients, 861,727 (2.6%) were newly diagnosed with ADRD (cohort 1), 373,798 patients (1.1%) were newly diagnosed with AD (cohort 2), and 395,319 patients (1.2%) were new users of cholinesterase inhibitors (cohort 3). The cohorts were not mutually exclusive. Overall, the three cohorts were similar in terms of demographics (table 1) with 75.1‐85.3% of patients aged 75+ and 61.5‐66.4% female. Common comorbidities (table 2) across the 3 cohorts include cardiovascular (CV) comorbidities such as myocardial infarction (34.1‐41.9%) and heart failure (39.8‐51.4%), diabetes (38.5‐41.6%), arthritis (44.0‐46.6%), stroke (28.9‐34.4%) and anxiety/depression (48.6‐54.5%). Co‐medications received (table 3) such as anti‐hypertensives, lipid modifying drugs, anti‐diabetics, systemic corticosteroids, and anti‐depressants reflect these conditions.ConclusionExtensive understanding of a drug’s real‐world target population can inform generalizability of clinical trial results and highlight unaddressed risk. This study stresses the importance of studying new AD drugs in populations with a history of CV risk, diabetes and stroke as well as those that may be immunocompromised due to treatments with systemic corticosteroids.
A Twin Analysis of AD Brain Signatures and Abnormal White Matter
Authors: Williams McKenna E. , Fennema‐Notestine Christine , Lin Shu‐Ju , Gillespie Nathan A. , Franz Carol E , Kremen William S. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) and vascular disease frequently co‐occur and may interact additively or synergistically on risk for cognitive decline, though the degree of shared overlap between these pathologies remains unclear. Our group has demonstrated the utility of AD signatures, or composite MRI metrics in brain regions associated with AD pathology, for prediction of AD‐related changes beginning in midlife. Our novel signature based on gray matter mean diffusivity (MD) aided 12‐year prediction of incident mild cognitive impairment among cognitively unimpaired adults in their 50s, captured unique phenotypic and genetic variance not otherwise explained by an AD signature based on cortical thickness/volume or general brain aging, and robustly predicted thickness/volume signatures over a decade later. Here, we leveraged twin data from the Vietnam Era Twin Study of Aging (VETSA) to delineate shared and unique genetic and environmental influences on two AD signatures and white matter hyperintensities (WMHs), which have been consistently linked to vascular origin.MethodParticipants were 512 men from the VETSA (age = 67.52, SD = 2.60). Our validated thickness/volume signature, novel MD signature based on the same brain regions as the thickness/volume signature, and WMH volume were used in biometrical twin analyses to examine their phenotypic, genetic, and environmental relationships. We adjusted each AD signature for an MRI‐based measure of brain age to detect associations with WMH that were specific to AD‐related brain regions versus general brain aging. We also examined regional WMH parcellations.ResultPhenotypic and genetic correlations demonstrated significant associations between the MD signature and WMH (rp = 0.26 [95% CI: 0.15, 0.36]; rg = 0.34 [95% CI: 0.10, 0.57]). In contrast, phenotypic and genetic correlations between the thickness/volume signature and WMHs were nonsignificant. Environmental correlations between each AD signature and WMH were similarly nonsignificant. Results were similar for each WMH parcellation, suggesting global WMH effects.ConclusionA gray matter MD signature and WMHs share significant genetic influences, whereas a thickness/volume signature was not associated with WMHs. AD signatures based on brain microstructure, such as the MD signature, may capture very early AD‐related and vascular‐related changes that are not captured by a macrostructural signature at the same timepoint.
Educational Attainment and Risk of All‐Cause Dementia, Vascular Dementia, and Alzheimer’s Disease – A Population‐Based Twin Study
Authors: Schwarz Claudia , Iso‐Markku Paula , Palviainen Teemu , Kaprio Jaakko , Vuoksimaa Eero 
Published: December 2023

AbstractBackgroundMost studies on the association between educational attainment and dementia have been conducted in unrelated individuals. Dementia‐discordant twin pairs can inform if the protective effect of education on dementia is evident when controlling for environmental and genetic effects. We investigated the association of educational attainment on all‐cause dementia, vascular dementia (VaD), and Alzheimer’s disease (AD) mortality in a population‐based sample of dizygotic (DZ) and monozygotic (MZ) pairs.MethodParticipants were from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975 (N = 29,784; mean age = 36.9±14.9years). Education was coded as <12 years versus ≥12 years. Registry‐based cause of death data until year 2020 was based on the International Classification of Diseases. We ran individual‐level cox proportional hazard models with sex as a covariate and conditional within‐twin‐pair models for education predicting all‐cause dementia, VaD, and AD mortality. We report hazard ratios (HR) with 95% confidence intervals (CI).ResultIn individual‐level analyses higher education was associated with a decreased risk of all‐cause dementia (HR = .935, 95%CI = .934;.936, p<.001) and VaD (HR = .638, 95%CI = .637;.640, p<.001), but with an increased risk of AD (HR = 1.276, 95%CI = 1.275;1.277, p<.001). In co‐twin analyses of discordant DZ and MZ twin pairs, co‐twins with higher education had lower – although non‐significant – risk of all‐cause dementia (N = 52, HR = .688, 95%CI = .319;1.481, p = .339) or AD (N = 36, HR = .600, 95%CI: .218;1.651, p = .323). Co‐twin analyses were not done for VaD due to small number of discordant pairs (N = 6).ConclusionThis large population‐based sample showed that higher education is related to lower risk of all‐cause dementia and VaD mortality. Unexpectedly, higher education was related to higher AD mortality, but discordant twin pair analyses were informative regarding this counterintuitive result. This case‐control design, controlling for genetic and environmental effects, did not support any causality from higher education to higher AD risk. Despite the large sample, twin pairs – especially MZ twins – discordant for dementia are rare. Meta‐ or mega‐analysis of multiple large twin studies is needed to clarify if secondary education is related to lower risk of dementia, VaD, and AD mortality when controlling for genetic effects.
Modifiable dementia risk factor associations with AT(N) biomarkers: Findings from the European Prevention of Alzheimer’s Dementia study
Authors: Roccati Eddy , Bindoff Aidan D , Collins Jessica M , Eastgate Joshua , Borchard Jay , Alty Jane E , King Anna E , Vickers James C , Carboni Margherita , Logan Chad , Consortium EPAD 
Published: December 2023

AbstractBackgroundThere is strong evidence that targeting modifiable risk factors can maintain and improve cognitive function, as well as reducing risk for Alzheimer’s disease (AD) and other forms of dementia. Further, a discrete AT(N) profile exists for hallmark biomarkers: amyloid β (A), p‐tau (T) and neurodegeneration (N), to discriminate between AD and non‐AD pathological changes. Despite evidence of a biologically defined AD continuum and modifiable risk amelioration, there is a paucity of studies investigating modifiable risk factors with respect to AT(N) biomarkers. The aim of this study was to investigate how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD.MethodParticipants were drawn from the European Prevention of Alzheimer’s Disease (EPAD): a prospective, multicentre, pan‐European cohort study. Eligible participants underwent clinical and neurological assessments, brain magnetic resonance imaging, cerebrospinal fluid (CSF) collection, neuropsychological assessment and completed a variety of demographic, clinical, medical history and lifestyle surveys for 10 binary modifiable risk variables. Data were analysed via the NeuroToolKit Application (NTKApp, BetaVersion, 2022). Generalized additive models with penalized regression splines were used to model the associations between modifiable risk factor adherence and AT(N) biological criterion: A (CSF amyloid‐β 42 [Aβ42 pg/mL]); T (CSF phosphorylated‐tau 181 [p‐tau 181 pg/mL]); N (total hippocampal volume [mm3]).ResultOf the 2737 participants included, 56% were female (n = 1526), 39% had at least one APOE ε4 allele (n = 1598), with an average age of 66.0 years and 14.4 years of education. Adjusting for age, sex and APOE carrier status: age, APOE and traumatic brain injury (TBI) were significantly associated with CSF Aβ42; age, APOE, body mass index (BMI) and exercise were significantly associated with CSF p‐tau181; and age, sex and education were significantly associated with total hippocampal volume.ConclusionModifiable risk factors of less education, less exercise, TBI and higher BMI were all significantly associated with increased AD biomarker burden. Our results support previous studies identifying associations between modifiable risk factors and AD and suggest that early intervention strategies focused on education and lifestyle factors and improvements in prevention and treatment of TBI may modify risk profiles associated with cognitive decline.
Using depth sensors for a fall risk prediction system for socially vulnerable older adults with cognitive impairment
Authors: Demiris George , Harrison Sean L , Richmond Therese S , Skubic Marjorie , Hodgson Nancy A 
Published: December 2023

AbstractFalls and fall‐related injuries are significant public health issues for adults 65 years of age and older. Over a third of older adults (OA) fall each year and 10‐20% of falls result in serious injuries such as fractures and head trauma. Cognitive impairment is a leading risk factor for falls in OA. Over 60% of OA with MCI fall annually – two to three times the rate of those without cognitive impairment. OA living in low‐resource neighborhoods with poor housing conditions have twice the risk of falling. We have developed a technology‐based intervention called Sense4Safety that facilitates fall risk management and fall risk reduction for older adults (OA) with cognitive impairment living in low‐resource communities. Specifically, the intervention is designed to to 1) identify escalating risk for falls real‐time through in‐home passive sensor monitoring using depth sensors; 2) employ machine learning to inform individualized alerts for fall risk; and 3) link OA with a nurse tele‐coach who guides them in implementing evidence‐based individualized plans to reduce fall‐risk. The nurse coach is accessible via video‐conferencing or phone to discuss fall prevention and risk reduction strategies with the OA and their trusted other depending on the patterns identified in sensor‐detected changes in functional mobility and gait. The measurable primary outcomes include number of fall and near‐fall events, number of fall‐related hospitalizations, functional mobility, self‐reports of fear of falling and perceived independence. We have conducted an initial feasibility study of the intervention with 10 older adults in low income housing settings for a period of 3 months. The Sense4Safety intervention has the potential to become a feasible and cost‐effective approach to increase safety and quality of life for community dwelling low income OA with cognitive impairment and prevent or reduce falls. Currently, in most cases fall risk is addressed only after an adverse event has occurred or cognitive decline has progressed significantly. This intervention changes that paradigm to maximize safety and promote aging in place.
Network‐based pipeline guides knowledge‐driven prioritization and validation of therapeutic target discovery for Alzheimer’s disease
Authors: Min Yuhao , Wang Xue , Gao Junli , Zhang Cheng , Ung Choong , Chalk Jessica L , Correia Cristina , Golde Todd E , Reddy Joseph S. , Carrasquillo Minerva M. , Zhang Ke , Allen Mariet , Li Hu , Ertekin‐Taner Nilufer 
Published: December 2023

AbstractBackgroundContext‐specific networks can capture functionally important genes that may not be differentially expressed. Leveraging seven different gene expression datasets of Alzheimer’s disease (AD) and healthy control brains, we constructed a novel pipeline that includes such network analysis, augmented by in vivo validations and in silico drug repurposing to facilitate prioritization of AD therapeutic targets.MethodWe utilized publicly available gene expression data from 733 AD and 454 control brains across 7 datasets and the NetDecoder (PMID: 26975659) network biology platform to build context‐specific networks. Based on the known protein‐protein interaction and gene expression correlations, information flow from the top differentially expressed genes (DEG) to transcriptional regulator genes was calculated using a process‐guided flow algorithm. Genes with the greatest informational flow changes across AD cohorts were systematically prioritized. We next validated these genes in a medium‐throughput screen of a tau‐transgenic Drosophila model (PMID: 11408621). Further, we identified existing small‐molecule drugs to target the candidate genes utilizing curated databases.ResultsA total of 14 context‐specific networks were constructed across 7 datasets. We found AD‐related genes, such as APP, to have high flow differences between AD and control networks and high connectivity. Notably, many such genes were not DEGs between AD and control, suggesting that the information flow captures novel aspects of AD pathophysiology. We nominated 224 unique genes with the greatest flow differences for functional validation. We screened 111 of the 224 candidate genes with readily available, high‐confidence orthologs in Drosophila. We identified genes that suppress (N = 68) or enhance (N = 27) tau‐related neurodegeneration in this model. We confirmed the effects of previously nominated genes, such as HDAC1, which enhances tau‐neurodegeneration if overexpressed and suppresses it if knocked down. We also identified and validated additional therapeutic targets. Lastly, we applied a network‐proximity‐based algorithm and identified small molecule drugs for the candidate genes.ConclusionWe present a novel pipeline that integrates analytic approaches, experimental validation, and drug repurposing to facilitate therapeutic discovery in AD. We applied this pipeline and nominated previously known and novel genes implicated in AD pathogenesis. Our pipeline demonstrates a cross‐species, systems‐level approach to therapeutic nomination in AD and related neurodegenerative diseases.
Stress and hypertension self‐care pilot study for Black women caregivers of people living with Alzheimer’s disease and related dementias
Authors: Wright Kathy D , Adams Ingrid K Richards , Helsabeck Nathan P , Ana Wong C , Ibrahim Omar , Kim Bohyun , Moss Karen O , Rose Karen M , Maryanna Klatt D 
Published: December 2023

AbstractBackgroundThis National Institutes on Aging study protocol (R21AG077069‐01 NIA) will test a behavioral intervention, Mindfulness in Motion plus the Dietary Approaches to Stop Hypertension (MIM DASH), to promote hypertension self‐care in African American women caregivers of people living with Alzheimer’s disease and related dementias.MethodTwenty‐eight participants will be randomized to MIM DASH or Alzheimer’s Association Caregiver Training groups, delivered 8 weekly, 1‐hour group sessions via telehealth (video and telephone access). Data are collected at baseline, 3 and 9 months that include a) psychosocial surveys and Healthy Eating Index—DASH score and b) blood pressure, hair cortisol, and an objective stress reactivity/stress resilience battery.ResultMIM DASH will be feasible and acceptable, and will decrease caregivers’ stress and improve quality of life; higher stress resilience will enhance the relationship between MIM DASH and intervention adoption while higher stress reactivity will diminish this relationship.ConclusionSubstantive contributions to the science of behavior change, design of self‐care interventions, and the adoption of healthy behaviors will be achieved. Results will inform infrastructure for a larger trial to reduce health disparities among African Americans.