bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to a lifestyle intervention ‐ self‐efficacy as crux of the matter?Analysis of AgeWell.de as multi‐domain lifestyle intervention against cognitive decline
Authors: Wittmann Felix Georg , Pabst Alexander , Zülke Andrea , Luppa Melanie , Wiese Birgitt , Hoffmann Wolfgang , Frese Thomas , Gensichen Jochen , König Hans‐Helmut , Kaduszkiewicz Hanna , Thyrian Jochen René , Riedel‐Heller Steffi G. 
Published: January 2025

AbstractBackgroundRecent research on preventing cognitive decline has focused on lifestyle interventions, with first studies indicating cognitive benefits and suggesting a positive link between adherence to the interventions and their effectiveness. The purpose of this study was to analyse possible predictors of this very adherence to single components of a multi‐domain lifestyle intervention.MethodsA total of n = 317 participants of the intervention group were included, characterized with an age ≥60 (mean age 68.9) and an increased risk of dementia (CAIDE score of ≥9). Generalized linear regression models were used to regress four predictor blocks (sociodemographic factors, cognitive and psychosocial predictors, lifestyle factors and chronic conditions, all assessed at baseline) on the adherence to each of four components of AgeWell.de (nutritional counselling, enhancement of social and physical activity and cognitive training). Adherence was operationalised as mean score of seven time points at which a study nurse assessed the degree of goal achievement per component. The goals were set individually at beginning of the intervention.ResultsStrengthening effects on adherence were found for higher education, unimpaired mental state and higher self‐efficacy. Increasing age, reporting depressive symptoms, smoking and partwise higher body mass index were instead negatively associated with adherence. No effect was found for chronic conditions.ConclusionThe study has identified both strengthening and mitigating predictors of adherence. This is relevant to future intervention designs aimed at enhancing adherence as a pivotal aspect for effectiveness. While age or education remain non‐modifiable, self‐efficacy emerge as a promising predictor. In light of optimizing the efficacy of forthcoming lifestyle interventions, a reasonable approach may involve the incorporation of strategies for enhancing self‐efficacy within the study design.
Drug‐related problems among older adults with Mild Cognitive Impairment and dementia receiving care at Multi‐specialty Interprofessional Team‐based (MINT) memory clinic
Authors: Sharma Rishabh , Lee Linda , Chang Feng , Patel Tejal 
Published: January 2025

AbstractBackgroundUp to 30% of hospitalizations in older adults living with Mild Cognitive Impairment (MCI) and dementia are attributed to drug‐related problems (DRPs), including adverse drug reactions, drug interactions, potentially inappropriate medication (PIM) use, and medication non‐adherence. This study categorizes the identified DRPs according to the Pharmaceutical Care Network Europe (PCNE) Classification for DRPs version 9.1.MethodsA cross‐sectional study was carried out with older adults receiving care for MCI or dementia at an Interdisciplinary memory clinic over eight months. The study employed four tools: the Medication Appropriateness Index (MAI), and the Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist, Beers Criteria 2023, and Screening Tool of Older Persons Potentially Inappropriate Prescription (STOPP) 2023 to conduct a medication review. Identified DRPs were categorized according to their types and root causes with the PCNE classification system, version 9.1.ResultsForty‐four participants (45.5% female, n = 20) were enrolled. The average age of the study participants was 80.2 years (standard deviation (SD) 6.2). Most of the participants (61.4%, n = 28) had six or more comorbidities ((mean ± SD) 6.7 ± 3.4). A total of 375 medications were prescribed to the 44 study participants. The median number of medications per day was 7.5 (interquartile range (IQR): 6 per day). A total of 119 DRPs were detected in 36 patients, with an average of 2.7 DRPs per patient. The most common type of DRP was within the classification of treatment safety, accounting for 63% of the reported DRPs (n = 75), followed by treatment effectiveness (15.9%, n = 19). The most common cause of DRPs noted was inappropriate drugs according to guidelines/formulary (43.6%, n = 52), followed by an inappropriate combination of drugs, or drugs and herbal or drug‐drug interaction (21%, n = 25) from the drug selection category. A total of 53 recommendations were made by the pharmacist in the medical records for the study participants.ConclusionThe high prevalence of DRPs, notably those involving treatment safety and inappropriate drug selection, emphasizes the importance of medication reviews and tailored interventions to improve medication management and safety in this at‐risk population.
Cross‐national harmonization of cognitive impairment and dementia diagnosis across US and Latin American populations
Authors: Llibre‐Guerra Jorge J. , Weiss Jordan , Li Jing , Soria Chris , Rodriguez‐Salgado Ana M , Llibre‐Rodriguez Juan J. , Jiménez‐Velazquez Ivonne Z. , Acosta Daisy M , Liu Mao‐Mei , Dow William H 
Published: January 2025

AbstractBackgroundCross‐national comparisons of dementia prevalence are essential for identifying unique determinants and cultural‐specific risk factors, but methodological differences in dementia ascertainment across countries hinder global comparisons. This study maps the 10/66 Dementia Research Group algorithm for dementia ascertainment, widely used and validated in lower‐ and middle‐income countries, to the U.S.‐based Aging, Demographics, and Memory Study (ADAMS), and validates it for use in the U.S.MethodsWe conducted pre‐statistical harmonization across the ADAMS and the 10/66 studies in Latin America to identify common measures, which were then utilized to develop a modified 10/66 algorithm. We computed dementia probabilities using the modified 10/66 algorithm and the optimal threshold for dementia ascertainment was established by maximizing sensitivity and specificity against ADAMS' clinical gold standard diagnosis. We then compared this algorithm to a TICS‐based algorithm developed in ADAMS and commonly used in the U.S. Health and Retirement Survey. Further analysis included an examination of the age‐adjusted educational gradients in predicted dementia prevalence, allowing for a comprehensive assessment of the modified algorithm’s validity and its comparative performance.ResultsThe sample comprised 5,649 adults ages 70 and over (539 from ADAMS and 5,109 from 10/66 studies).10/66 participants had a lower education level (60% had primary school or less) relative to the ADAMS cohort (69.8% possessed at least a high school education). The modified 10/66 diagnostic algorithm performed similarly in the 10/66 data as compared to the original 10/66 algorithm. In the ADAMS data, the modified 10/66 algorithm outperformed the TICS algorithm across several metrics: it demonstrated higher sensitivity (90% vs 77%), specificity (90% vs 74%), accuracy (90% vs 75%), and Area Under the Curve (AUC) (90% vs 76%). The modest ADAMS sample size precluded statistically precise comparisons by education, but education gradients in predicted dementia were broadly similar across algorithms.ConclusionsThe modified 10/66 algorithm effectively classifies dementia in US studies and is suitable for cross‐national comparisons, supporting its use for international studies. This facilitates future harmonization efforts of dementia diagnostic tools and enhances cross‐country dementia research.
A digital twin technique using external observational data to reduce sample sizes in clinical trials on Alzheimer’s disease
Authors: Andrews Daniel , Collins D Louis ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundRandomized placebo‐controlled trials (RCTs) are the gold standard to evaluate efficacy of new drug treatments for Alzheimer’s disease. For example, the United States FDA approved the brain amyloid‐targeting drug lecanemab following CLARITY AD, Biogen and Eisai’s Phase 3 RCT. However, recruiting enough participants for a high‐powered and demographically representative trial is difficult and expensive. Fortunately, historical patient data from existing external observational studies of a disease can help populate RCTs [Thorlund et al. (2020). https://doi.org/10.2147/CLEP.S242097]. We propose a new trial framework that uses an external study to source “digital twins” for each trial participant. Using computer‐simulated trials mimicking CLARITY AD’s demographics and 18‐month duration, we show that our digital twin trial (DTT) has increased power compared to a conventional RCT.MethodA continuous time linear mixed model tracked CDRSB change‐from‐baseline (CDRSBΔbl) trajectories in 670 ADNI participants satisfying CLARITY AD inclusion criteria [clinicaltrials.gov/study/NCT03887455]. To simulate an RCT, we resampled and added noise to participants’ data, generating a desired sample size of “recruited” participants who we randomized 1:1 to “drug” and “placebo” groups. We calculated participants’ CDRSBΔbl scores at 18 months and simulated the drug effect as a 25% reduction in CDRSBΔbl. For each participant in our DTT, we used Gower’s distance on demographic and clinical baseline variables to identify 20 most‐similar real ADNI participants (the digital twins) from our original 670. Each original ADNI participant’s 18‐month CDRSBΔbl was calculated using the model. A z‐score was then calculated for each DTT participant’s 18‐month CDRSBΔbl relative to their digital twins. T‐tests were used to evaluate DTT drug vs. placebo group difference in mean z‐score and, separately, RCT group difference in mean 18‐month CDRSBΔbl. We simulated each trial 1,000 times. Power is the proportion of simulations with a statistically significant treatment group difference.ResultFigure 1 shows that 90% power is reached with approximately 500 fewer recruited participants in simulated DTTs (∼1,600 participants) compared to RCTs (∼2,100 participants).ConclusionDTTs might require substantially fewer recruited participants to achieve the same power as conventional RCTs. This sample size reduction could facilitate recruitment for trials on Alzheimer’s and in rare diseases with low patient numbers.
Effectiveness of a Local Recruitment Registry
Authors: Birnbaum Adam I , Grant‐Freeman Zion T , Grill Joshua D , Hoang Dan , Gombosev Adrijana , Gillen Daniel L 
Published: January 2025

AbstractBackgroundRecruitment registries are tools to decrease the time and cost required to identify and enroll eligible participants into clinical research. Despite their potential to increase the efficiency of accrual, few analyses have assessed registry effectiveness. We investigated the outcomes of study referrals from the Consent‐to‐Contact (C2C) registry, a recruitment registry at the University of California, Irvine.MethodWe categorized the outcome of study referrals as: (1) unable to reach, (2) declined to participate, (3) phone screened but ineligible, (4) consented but ineligible or (5) consented and enrolled. We assessed overall effectiveness of the registry via the empirical distribution of referral outcomes. To assess associations between participant characteristics and referral outcomes we used a binary logistic generalized linear mixed‐effects model with study‐specific random intercepts, restricting the analysis to the outcome of the first study referral for each participant in the subset of referrals for which we had complete subject‐level data (n = 3,238). We treated any referral leading to obtaining participant consent as a success. We tested for an association between the odds of successful first referral and score on the research attitudes questionnaire (RAQ) via a 2‐sided Wald test.ResultThe C2C made 9,696 referrals to 60 studies. 2,805 (28.9%) of these referrals were successful, leading to participant consent. In 40% of referrals, the participant did not respond to contact and in 23.7% of referrals the participant declined. We estimated that participants who scored 5 points higher on the RAQ had 13% higher odds of successful first referral compared to otherwise similar participants (95% CI: 1.02,1.25, p = 0.015). Other factors significantly associated with successful enrollment included older age (OR = 1.10 per 10 years, 95% CI: 1.01,1.2, p = 0.024), female sex (OR = 1.28, 95% CI: 1.07,1.53, p = 0.008), and higher education (ref≤12 years; 13‐16 years: OR = 1.68, 95% CI: 1.16,2.44, p = 0.006; >16 years: OR = 1.77, 95% CI: 1.21,2.58, p = 0.003).ConclusionThese results suggest that the C2C is an effective tool in aiding accrual in ADRD clinical research and that the RAQ may be a meaningful predictor of referral outcomes.
Subjective Cognitive Decline is associated with blood‐plasma Neurofilament Light in cognitively normal older adults
Authors: Chapman Silvia , Cosentino Stephanie , Nosheny Rachel L. , Herman Mathieu , Brickman Adam M. , Simoes Sabrina 
Published: January 2025

AbstractBackgroundNovel plasma markers are increasingly accepted as indicators of Alzheimer’s disease and related dementia (ADRD) pathophysiology. The extent to which these markers map with clinical symptoms of disease remains unclear. A proposed early clinical symptom of ADRD is subjective cognitive decline (SCD), the experience that cognition has declined despite normal performance on objective assessment. Mapping the association between ADRD plasma biomarker concentrations and SCD will shed light on the links between pathophysiology and symptomology in the earliest stages of disease. This pilot study examines how SCD (self and informant based) associates with plasma p‐tau181, Aβ42, Aβ40 and neurofilament light chain (NfL) concentrations.MethodForty‐four (mean aged=68 years) cognitively unimpaired individuals and 41 informants were recruited from the Columbia University Alzheimer's Disease Research Center. Levels of plasma ADRD biomarkers (Aß42, Aß40, p‐tau181 and NfL) were measured on the Simoa HD‐X platform. SCD was measured with two dichotomous variables indicating whether there had been a decline in memory relative to previous ability reported by the participant and their informant. Eight unadjusted linear regression models examined self and informant SCD as predictors of each plasma marker. Models were then adjusted for relevant covariates, and interactions with age and sex were considered.ResultAs reported in Table 1, unadjusted models showed that self‐reported SCD was associated with higher NfL. Informant‐reported SCD was also associated with higher plasma NfL as well as higher p‐tau181. Effect sizes were reduced after adjustment and only self‐reported SCD remained associated with higher NfL. Male sex was associated with greater levels of NfL in those who had SCD.ConclusionSCD had stronger associations with a marker of neurodegeneration than amyloid or tau burden. Findings are in line with previous studies showing that NfL has a close relationship with clinical impairments such as cognitive decline. Sample size and type of assay utilized in this study could have limited our ability to see associations with tau and amyloid burden. Futures studies should examine how the combination of plasma markers and early clinical symptoms can aid the predictive utility of plasma markers for onset and progression of clinical symptoms.
Engaging community stakeholders to develop a Dementia Risk Reduction Protocol for primary care settings assisting underserved mid‐aged and older adults
Authors: Souza‐Talarico Juliana Nery , Ashida Sato , Newman Larry 
Published: January 2025

AbstractBackgroundReducing dementia risk factors at mid‐life by 10‐25% can prevent an estimated 1‐3 million dementia cases worldwide. However, implementation of dementia risk reduction (DRR) is limited, particularly in underserved communities. Barriers include lack of awareness and access to appropriate services. Engaging community stakeholders is crucial for adapting and incorporating interventions that are feasible, acceptable, and sustainable into community care. We aimed to involve local stakeholders to develop a DRR protocol suitable for primary prevention in underserved communities.MethodsCollaborating with a university‐affiliated Mobile Clinic (U‐MC) offering free health services, we reached out to middle‐aged and older adults in two underserved communities. A Stakeholder Advisory Board (SAB) was formed, comprising eight individuals, including community members, primary care providers/students, researchers, and aging organization representatives. Relying on the recommendations of the UsAgainstAlzheimer’s risk reduction workgroup, the SAB employed the ACTT framework (Actions, Context, Target, and Time) to delineate DRR strategies.ResultsOver five bi‐weekly meetings, the SAB designed an action plan for dementia risk screening (11 risk factors), education and follow‐up (Actions), involving students and primary care professionals (Actors) in community health assessments (Context) for individuals over 40 (Target). Culturally‐sensitive educational materials with local resources were designed to support detected risks, with annual monitoring (Time). Insights into the SAB operations like group dynamics and partnership efficacy were also evaluated to optimize collaborative efforts in healthcare delivery.ConclusionThe active collaboration with community stakeholders facilitated the development of a tailored, evidence‐based DRR protocol, reinforcing the importance of local input in creating feasible and sustainable health interventions in underserved communities. This customized approach shows promise for wider adoption in similar communities, aiming to promote primary prevention and substantially decrease the incidence of dementia.
Sociodemographic and risk factor analysis of the SMRUTHI India: a cohort of at risk elderly Indians for primary prevention of dementia
Authors: Gupta Anu , Sinha Abhik , Sharma Varuna , Raina Sunil K , Roy Subarna , Baidya Subrata , Anand P K , Nehra Ashima ,   Nilima N , Khan MA , Vishnu Venugopalan Y , Srivastava MV Padma 
Published: January 2025

AbstractBackgroundAround 40% of dementia cases can be prevented or delayed by modifying the risk factors. The SMRUTHI INDIA study will be conducted to establish a trial‐ready cohort of elderly Indians who are at high risk of developing dementia.MethodThe present study utilizes the design of “Cohort Multiple Randomized Controlled Trial” (cmRCT) with in‐built provisions to conduct multiple randomized controlled trials (Figure 1). A large cohort of the rural population (4 zones of India, through established Indian Council of Medical Research ‐ Model Rural Health Research Units) has been established aiming to explore risk factors for dementia and follow them systematically with yearly neuropsychological evaluation for 5 years. Active screening is ongoing at multiple sites of the project. Detailed neuropsychological testing and risk factor analysis are in progress. An ancillary study proposes to design a multimodal “care bundle” for the prevention of dementia, which is culturally tailored and context‐specific to the Indian population (Figure 2). This intervention will undergo testing for feasibility in the hospital setting at the central coordinating site, through a pilot randomized controlled trial (six months). The curated care bundle will be the first intervention tested in phase 2 of SMRUTHI INDIA cmRCT cohort.ResultWe have recruited 432 (South zone 236, East zone 130, West zone 42, North zone 24) participants so far. The mean age is 66.1 ± 7.6 years. 258 (59.7%) participants are females. 266 (69.1%) have no formal education. Only 109 (25.3%) are actively employed. 374 (86.6%) are married, with 259 (60.1%) living in a joint family. 104 (36.1%) are overweight or have grade 1 obesity. Hypertension is present in 136 (31.5%), active smoking in 131 (30.3%), diabetes in 59 (13.7%), current alcohol consumption in 52 (12%), uncorrected vision loss in 33 (7.7%), hearing loss in 7 (1.6%), known coronary artery disease in 2 (0.5%).ConclusionSMRUTHI‐India study intends to find the potential of sustainable multimodal interventions for the prevention of dementia among Indians with rural background. Low education is highly prevalent. Obesity, hypertension and smoking affect nearly one‐third of the participants and could represent important targets for dementia prevention in India. (CTRI/2014/01/061172)
Perceived adverse maternal control during childhood and striatal volume in healthy older adults: Differences between APOE ε4 carriers and non‐carriers
Authors: Gheorghe Delia A , Kuenzi Morgane , Bauermeister Sarah 
Published: January 2025

AbstractBackgroundEarly adversity has been reported as a risk factor for dementia. Adverse maternal control (MC) during childhood is believed to impact neural developmental pathways. Here we studied the associations between adverse MC and the volume of the dorsal striatum in older adults given evidence from the childhood adversity literature of structural reductions and altered reward processing. The contributing roles of APOE ε4 status together with multiple other known risk factors in brain aging were analysed.MethodWe analysed data from the MRC NSHD Insight 46 study on the Dementias Platform UK Data Portal (N = 394, 48% female, 70 years). MRI acquisition and APOE ε4 genotyping are described in published cohort papers. Bilateral volumes of the caudate nucleus and putamen were obtained using the FMRIB Software Library. MC was quantified using the Parental Bonding Instrument (PBI). Using k means clustering, participants were grouped in low, medium, and high MC groups. Analyses controlled for sex, age, socioeconomic status in late adulthood and childhood, speed of pubertal growth, birthweight, BMI and MMSE score at the time of brain scanning.ResultMultivariate tests were followed up with Bonferroni‐corrected comparisons. Smaller bilateral caudate nuclei and reduced wellbeing were found in the high MC group compared to the low MC group. MC effects on the brain were not mediated by wellbeing. When considering the role of APOE ε4, Roy’s largest root revealed a significant interaction between MC and APOE ε4 status. Corrected follow‐up comparisons showed that in non‐carriers only, high MC was associated with smaller left caudate, left putamen volumes as well as reduced wellbeing, compared to the low MC group. Separately, in a smaller sample of APOE ε2 carriers (N = 51), the left caudate volume was smaller in high MC group.ConclusionOur study showed that regions implicated in reward processing are smaller in individuals who experienced adverse MC during development. These effects were present in APOE ε4 non‐carriers. APOE ε4 effects are detectable in the dorsal striatum in later life in preclinical populations. Whether genotype masks stress effects on the brain in APOE ε4 carriers is yet to be established.