bluuebunny/crossref_metadata_2025_split huggingface dataset:
AlzPED: An Open Science Tool to Increase Rigor in Therapeutic Efficacy Testing in Alzheimer’s Animal Models
Authors: Chakroborty Shreaya , Viswanathan Jaya , Gallofre Maria Fe Lanfranco , Martin Zane , Petanceska Suzana S , Refolo Lorenzo M 
Published: January 2025

AbstractBackgroundPositive findings from testing therapeutics in AD animal models are often not translated to effective treatments due to the poor methodological rigor and inadequate reporting practices of therapeutic efficacy studies. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), developed by the NIA, is a searchable and publicly available knowledgebase that prioritizes and promotes the use of rigorous methodology to ameliorate this translation gap. Through a checklist of experimental design elements – the Rigor Report Card ‐ AlzPED highlights reporting recommendations and standards while providing a practical tool to help plan rigorous therapeutic studies in animals. AlzPED also serves as a platform for creating citable preprints, including negative findings to mitigate the publication bias favoring positive reports.MethodsUsing key word‐driven literature searches published studies are acquired and curated by two subject‐matter experts for bibliographic details, funding source, study goals and principal findings, data on relevant translational criteria like therapy type, therapeutic agent, therapeutic target, animal models, and AD‐related outcome measures. Rigor is assessed with the Rigor Report Card.ResultsAlzPED hosts curated summaries from 1400 published preclinical therapeutic studies in AD animal models, and data related to 274 therapeutic targets, 1206 therapeutic agents, 226 animal models, more than 2500 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from 1400 published preclinical therapeutic studies demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation (4% of curated studies), blinding for treatment (10%), randomization (32%), balancing for sex (24%), inclusion/exclusion criteria (7%). All analytics are shared on AlzPED under the principles of open science.ConclusionsRigorous experimental design and transparent reporting are essential to inform future research, science policies, and successful clinical trials. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of drug testing data to the clinic.
Longitudinal Associations between Sensory Difficulty and Motor Impairment and Incident Dementia in the National Health and Aging Trends Study
Authors: Davoudi Anis , Dougherty Ryan J. , Wanigatunga Amal A , Agrawal Yuri , Wang Hang , Reed Nicholas S , Ehrlich Joshua R , Gross Alden L. , Schrack Jennifer A 
Published: January 2025

AbstractBackgroundImpairments in sensory and motor function are common and have been independently linked with higher risk of dementia in older adults. Yet, there is limited information associated with the increasing number of such impairments and dementia risk. This study investigated longitudinal associations between sensory and motor impairment and dementia in older adults.MethodWe used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community‐living Medicare beneficiaries aged 65 years and older. Baseline sensory impairments were defined based on self‐reported vision and hearing loss indicators. Baseline motor impairments were defined based on performance in gait, repeated chair stands, standing balance, and grip strength tests. Multivariable Cox regression models were used to evaluate the hazard ratio of incident dementia from baseline (2011) to 2022.ResultA total of 3847 participants without dementia at baseline were included (weighted mean age 73.9 (95% CI: 73.7‐74.1) years old and 56% (95% CI: 54.1‐57.9) female). Compared to those without impairment in each specific domain, hazard ratios for incident dementia were 1.02 (95% CI 0.89‐1.16, p = 0.82) for hearing impairment, 1.34 (95% CI 1.13‐1.60, p = 0.001) for vision impairment, 1.31 (95% CI 1.18‐1.47, p<0.001) for chair stand impairment, 1.23 (95% CI 1.10‐1.39, p<0.001) for standing balance impairment, 1.49 (95% CI 1.34‐1.67, p<0.001) for gait speed impairment, and 1.31 (95% CI 1.13‐1.51, p<0.001) for grip strength impairment (Table 1). Additionally, compared to participants with no impairments, the hazard ratio for incident dementia for those with three impairments was 1.44 (95% CI 1.14‐1.82, p = 0.003), with four impairments was 1.92 (95% CI 1.50‐2.47, p<0.001) and with 5‐6 impairments was 1.96 (95% CI 1.50‐2.56, p<0.001) (Table 1, Figure 1).ConclusionIn this cohort study of US Medicare beneficiaries, vision and motor impairment as well as a higher number of impairments were associated with elevated risk of dementia. These findings underscore the cumulative burden of sensory and motor impairments on incident dementia. A better understanding of the temporality and longitudinal effect of sensory and motor impairments on incident dementia may help inform future targeted interventions.
The development and validation of the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI): a disease‐specific caregiver‐reported outcome measure for use in clinical trials
Authors: Shupe Christina , Seabury Jamison , Varma Anika , Weinstein Jennifer , Engebrecht Charlotte , Rosero Spencer , Irwin Charlotte , Dilek Nuran , Arky Abigail , Santos Elizabeth , Heatwole Chad 
Published: January 2025

AbstractBackgroundIn preparation for therapeutic trails involving patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), there is a need for valid, disease‐specific caregiver‐reported outcome (CRO) measures capable of tracking symptomatic burden in response to therapy over time. CROs are useful tools in clinical trials for individuals with AD, MCI, and dementia who are unable to self‐report. In addition, CROs are accepted by the United States Food and Drug Administration to support regulatory claims. This research involved the development and validation of the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI): a regulatory grade, disease‐specific CRO for use in detecting symptomatic changes in individuals with AD, MCI, and dementia during therapeutic trials.MethodWe conducted semi‐structured qualitative interviews and a cross‐sectional survey with caregivers to identify the prevalence and relative importance of symptoms experienced by individuals with AD, MCI, and dementia. We selected symptom questions for the ADCR‐HI based on their relevance and potential responsiveness to therapeutic intervention. We performed beta interviews with caregivers to determine the comprehensiveness, ease of use, and relevance of the instrument. Subsequently, we determined the reliability, known groups validity (Figure 1), and final internal consistency of the ADCR‐HI. We additionally conducted an area under curve (AUC) analysis using ADCR‐HI total scores (Figure 2).ResultInitial interviews were conducted with 15 caregivers of individuals with AD, MCI, or dementia. The cross‐sectional survey was completed by 324 caregivers. Beta interviews with 12 caregivers determined the instrument to be relevant and easy to use. The ADCR‐HI and its subscales displayed high test‐retest reliability over a 14 day period (n = 30) (Table 1). Known groups analysis (Figure 1) demonstrated the ability of the ADCR‐HI to differentiate between groups with greater disease severity.ConclusionThe ADCR‐HI is a regulatory‐grade, reliable CRO comprised of eight subscales that comprehensively measure an individual’s symptomatic burden through the perspective of the caregiver. The ADCR‐HI is available to support therapeutic trials and drug‐labeling claims as a valid clinical tool.
The MindMoves Trial: Effect of Lifestyle Physical Activity and Cognitive Training Interventions on Cognition in Older Women with Cardiovascular Disease
Authors: Halloway Shannon , Arvanitakis Zoe , Schoeny Michael E , Volgman Annabelle Santos , Pressler Susan J , Vispute Sachin , Wilbur JoEllen , Barnes Lisa L. 
Published: January 2025

AbstractBackgroundCardiovascular disease (CVD) increases the risk of cognitive impairment (CI), particularly in women. Physical activity and cognitive training can improve cognition, with potential interactive effects. The purpose of this study was to evaluate the efficacy of MindMoves, a 24‐week multidomain physical activity and cognitive training intervention, on cognition in older women with CVD.MethodThis randomized controlled trial (NCT04556305) with a 2×2 factorial design tested the independent and combined efficacies of Mind (tablet‐based cognitive training) and Move (lifestyle physical activity with goal‐setting and group meetings) on change in cognition (episodic memory, semantic memory, working memory, and executive function). Women (n = 253) aged 65 years and older with CVD and without CI at baseline were randomized to (1) Mind, (2) Move, (3) MindMoves, or (4) usual care. Intervention orientations were in‐person, and all other intervention activities were home‐based. From September 2020–December 2023, participants completed telephone neuropsychological tests and questionnaires at baseline, 24, 48, and 72 weeks.ResultParticipants were, on average, 72.4 years old at baseline (range = 65‐90), primarily of non‐Hispanic White (54%) and non‐Hispanic Black (38%) racial backgrounds, and 60% graduated college. A total of 86% (n = 218) of participants completed the 72‐week data collection. Attrition was not a function of intervention condition, sociodemographics, or baseline cognition (all p’s > .05). On average, all participants showed improvement in episodic memory and executive function. In multilevel mixed models adjusted for age, education, and racial and ethnic background, the main effects of Mind and Move, and the interactive effects (Mind*Move interaction), on linear change over 72 weeks were not statistically significant for any of the four cognition outcomes. In additional models that tested the intervention effects averaged across all follow‐up timepoints, none of the intervention conditions were associated with cognition.ConclusionAlthough participants improved in two domains of cognition, there were no differential effects of the intervention conditions (cognitive training and/or physical activity) in this cohort of older women with CVD. Future analyses will examine intervention effects on serum biomarkers that may provide additional insights of efficacy.
State‐level effect of Medicaid expansion on Alzheimer’s disease and related dementias mortality
Authors: Wing Jeffrey , Rajczyk Jenna , Strominger Julie , Singh Parvati 
Published: January 2025

AbstractBackgroundWith the rapid aging of the US population, the prevalence of dementia is projected to double. The enactment of the Affordable Care Act and Medicaid expansion could create opportunities for detection and classification of dementia. There are trends of increasing dementia mortality, however, it is unknown whether Medicaid expansion increased the reporting of dementia as the underlying cause of death (UCOD) or as a multiple cause of death (MCOD) among the elderly.MethodsState‐level Alzheimer’s disease and related dementias (ADRD) mortality data for those 65 years and older were downloaded from CDC WONDER for 2000‐2019. ADRD was classified as ICD‐10 codes: F01, F03, and G30. Staggered difference‐in‐difference analysis was done to estimate the ADRD mortality rate pre‐ and post‐Medicaid expansion. An overall average treatment effect for the treated (ATT) was estimated along with estimation for ATT by post‐period. Mortality measured as UCOD and MCOD were evaluated separately. Results were compared to all‐cause and cardiovascular disease (CVD) mortality for the same period.ResultsA total of 29 out of 50 states expanded Medicaid by 2019. Post expansion, ADRD mortality increased by 9.02 per 100,000 persons (95% CI: 1.81, 16.23). The change in mortality (UCOD) was most pronounced by two years post expansion, gradually increasing each year (two‐years post ATT: 10.02; 95% CI: 3.51, 16.52; five‐years post ATT: 13.58; 95% CI: 2.82, 24.34; Figure 1a). MCOD ADRD mortality demonstrated a similar pattern as UCOD ADRD mortality (ATT: 11.31; 95% CI ‐1.42, 24.05; Figure 2a). This trend was not observed across the same period for UCOD CVD mortality (ATT: 0.80; 95% CI: ‐12.42, 14.02) and the post‐expansion difference observed for UCOD all‐cause mortality lacked precision in comparison to dementia mortality (ATT: 7.43; 95% CI: ‐23.12, 37.98).ConclusionsADRD as the UCOD increased following state‐level Medicaid expansion, but this increase was not observed similarly for CVD mortality nor all‐cause mortality. Additionally, the same effect was not observed for ADRD as a MCOD. The lag between expansion and the increase in mortality may arise from increased detection through Medicaid supported care and in‐turn being listed or correctly identified as the underlying cause of death.
Physical activity and diet modify the sex specific association between neurotrophin single nucleotide polymorphisms and insomnia in late‐life
Authors: Gonzalez Hector L. , Schwartz Sarah , Rattinger Gail B. , Liu Yin , Drewel Mikaela , Mills Maddy , Buhusi Mona , Tschanz JoAnn T. 
Published: January 2025

AbstractBackgroundSleep disturbance is common in older adults at prevalence rates ranging between 30 ‐ 50% in the United States. Insomnia in late life is influenced by a wide array of genetic and lifestyle factors, some of which exhibit sex‐dependent effects. This study examined whether selected single nucleotide polymorphisms (SNPs) related to the neurotrophin, brain‐derived neurotrophic factor (BDNF), or its receptors and lifestyle factors, and their interactions were associated with the increased risk for sleep disturbance in older males and females.MethodThe Cache County Study on Memory and Aging, a longitudinal, population study, enrolled 4,057 cognitively healthy participants [56.7% female; mean (SD) age = 74.78 (6.75) years]. Sleep disturbance (39% endorsed) was determined by self‐report of insomnia. Adherence to the Mediterranean diet and physical activity (sedentary, light, moderate and vigorous) were based on mail‐in questionnaires. The following SNPs were examined as predictors of sleep disturbance in separate logistic regression models for males and females: rs6265 (BDNF Val66Met), rs56164415 (BDNF C270T), rs2289656 (NTRK2 receptor TrkB), and rs2072446 (NGFR p75NTR). Covariates included age, body mass index, education, APOE ε4 status, and depression.ResultSNPs for BDNF or its receptors were not associated with sleep disturbance. Males experienced an 18% reduced odds of sleep disturbance with increasing levels of physical activity (OR (95%CI) = 0.83 [0.71; 0.97]; p = .023), whereas greater adherence to the Mediterranean diet was associated with an 8% higher odds of reporting sleep disturbance (OR [95%CI] = 1.08 [1.00; 1.18]; p = .047). Among females a trend for an interaction (p = .088) between Val66Met and physical activity indicated those with the minor allele who engaged in sedentary‐to‐light physical activity exhibited a 45% higher risk of sleep disturbance compared to those with the minor allele and moderate‐to‐vigorous physical activity (p = .026).ConclusionLifestyle factors of physical activities and diet affect the BDNF gene‐insomnia association differently for older males and females. Future studies may further explore interventions affecting BDNF levels (e.g., physical activity) as one potential way to treat insomnia in older adults.
Lexicon of Dementia: A cross‐linguistic study of the impact of dementia terminology on cultural perceptions
Authors: Michael Mary Chi 
Published: January 2025

AbstractBackgroundLanguage serves as a powerful tool in shaping perceptions and reinforcing societal norms. Current understanding suggests that the language used to describe dementia can impact how the condition is perceived, understood, and addressed within various cultural contexts. Further, language can play a pivot role in shaping caregiving practices, willingness to seek medical care, and the openness, or lack thereof, to speak about the condition. Understanding these linguistic nuances, both across and within, languages is critical for fostering more effective, inclusive, and tailored approaches to addressing dementia.MethodTo understand how language influences cultural perceptions of dementia, we conducted interviews with linguists, medical anthropologists, health care professionals, care partners, and individuals living with dementia across five languages: Japanese, Mandarin, Swahili, Spanish, and Portuguese. We discussed terminology, regional nuances in language, stigma, misconceptions, care practices, communication strategies, and paths forward for addressing language and improving cultural perceptions. Interviews were supplemented with a comprehensive review of existing literature.ResultFrom our research we found that dementia terminology varies greatly across languages. In some, ‘dementia’ carries significant stigma, translating to ‘stupid’, ‘crazy’, ‘senile’, or other, similarly discriminatory terms. In other languages, there is no word for dementia at all, so the local language is mixed with English to describe memory or cognitive decline. Responses are similarly varied. Some cultures are making efforts to, or have already, changed discriminatory language around dementia. Others, particularly those without substantial dementia terminology, look to English to set a better standard.ConclusionAcross languages, experts concede that dementia terminology is an integral factor in perpetuating stigma, misinformation, and silence. But it doesn’t have to be. Language can also be used to drive positive change. By exploring the connection between language and cultural perceptions, and by studying the measures some have taken to address linguistic stigma, we can uncover valuable insights that inform a broader dialogue on effective and inclusive language for dementia.
Direct and indirect costs of dementia in Brazil
Authors: da Mata Fabiana A F , Ramos Ari Alex , Bertola Laiss , Suarez Thais , Ferri Cleusa P , Júnior Haliton Alves de Oliveira 
Published: January 2025

AbstractBackgroundIn Brazil, the dementia landscape is projected to intensify significantly, with the number of people living with dementia expected to more than triple by 2050. This anticipated surge underscores the urgency for health and social systems to strategize and prepare adequately. However, studies about costs related to dementia are very scarce in Brazil, making it difficult to understand better the financial impacts of the syndrome. Estimating the direct and indirect costs related to dementia, considering the reality of Brazil in its geographical diversity, is essential to understanding the reality of health resource allocation and, therefore, (re)direct resources to meet better the needs of people with dementia and their families. This study aims to estimate costs related to dementia in Brazil.MethodThis study is part of the ReNaDe (National Report on Dementia) project, a domiciliary survey conducted with 140 dyads of people with dementia and their respective caregivers in 17 municipalities in Brazil. We used the cost of illness study methodology to estimate costs. We collected data from the ReNaDe interviews and national records and presented estimates from societal and the Brazilian Public Health Systems (SUS) perspectives. Our total costs encompassed direct medical costs (hospitalizations, outpatient visits, and others) and indirect costs (for instance, the monetary value of informal caregiving hours) (Table 1). We did not consider direct social costs, given limited or inexistent information about cost and services utilization by people with dementia in Brazil. We used the replacement approach to estimate indirect costs.ResultThe monthly cost of dementia per individual increases with the syndrome’s progression (Table 2). Indirect costs, primarily associated with informal care provided by family or friends, constitute at least 73% of total expenses, irrespective of dementia stage and adopted perspective. For Brazil in 2019, dementia’s total annual cost was US$18 billion, with indirect costs comprising 78%.ConclusionThe average expenses per individual escalate with the advancement of dementia in Brazil. The pronounced prevalence of indirect costs accentuates the pivotal role that family caregivers assume in dementia care.
ß‐Hydroxy ß‐methyl butyrate, a muscle‐building supplement, restores neuronal plasticity in Alzheimer’s disease model
Authors: Paidi Ramesh Kumar , Pahan Kalipada 
Published: January 2025

AbstractBackgroundAlzheimer’s disease is the most dreaded multifactorial neurological illness for which there is currently no known treatment. Although the exact cause of AD is still unknown, several factors related to lifestyle, genetics, and environment are known to have a significant role in the disease’s development. Alzheimer’s disease is characterized by neuronal loss, neurofibrillary tangles, and senile plaques. Still, synapse loss is thought to be a major neuropathology associated with AD. β ‐hydroxy β ‐methyl butyrate (HMB) is a common muscle‐building supplement used by bodybuilders to enhance exercise‐induced increases in muscle development and strength. HMB is an extremely safe supplement that shows no negative effects even after prolonged use.MethodIn primary mouse hippocampal neuronal cultures, we first validated the effect of HMB in terms of neuronal plasticity and neuronal markers. Additionally, we gave six‐month‐old XFAD animals oral HMB for 30 days, and we used the T‐Maze, Barnes Maze, Novel Object Recognition, and locomotion tests to evaluate the animals' cognitive skills. In vivo pathway inductions were analyzed using western blotting and immunohistochemical studies.ResultIn the current study, HMB treatment prominently elevated neuronal plasticity markers like Glut N2A, Glu‐A1, Snap25, and PSD 95 in primary hippocampal cultures. HMB restores the cognitive malfunctions in 5xFAD AD mice; SNAP25 and PSD 95 expressions were increased following HMB administration. This was consistent with the phosphorylation of CREB and the increased calcium influx in the hippocampal region implicated in improving synaptic plasticity.ConclusionOur results indicate that HMB increases the expression of synaptic proteins and controls CREB phosphorylation, which could regulate neural plasticity and lead to cognitive recovery in AD models. Given that HMB is a strong, safe supplement, more research on its potential benefits for treating AD seems needed.