bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Incident Alzheimer's Disease in Older Community‐Dwelling Adults using Wrist Accelerometry and Deep Learning
Authors: Midroni Julie , Yu Lei , Rabin Jennifer S , Liu Xilin , Goubran Maged , Buchman Aron S , Bennett David A. , Lim Andrew 
Published: January 2025

AbstractBackgroundDrugs targeting Alzheimer's disease (AD) pathology are likely to be most effective in the presymptomatic stage, where individuals harbor AD pathology but have not manifested symptoms. Neuroimaging approaches can help to identify such individuals, but are costly for population‐wide screening. Cost‐effective screening is needed to identify those who may benefit from neuroimaging, such as those at risk of developing clinical disease. We present a deep learning algorithm that uses accelerometry recordings to predict clinically diagnosed AD in dementia‐free patients.MethodParticipants were from The Memory and Aging Project (MAP), a longitudinal cohort study of older adults focused on aging and dementia. As part of this study, participants were asked to wear a wrist accelerometer for ten days. We designed a feedforward neural network that synthesizes clinical and accelerometric features to predict clinical AD. Clinical features were selected based on ease of collection, and included age, sex, education, social isolation and purpose in life. The dataset included participants without dementia at the time of recording, who survived for and had a known clinical AD outcome within five years of the recording.ResultThe training dataset consisted of 875 unique patients. The test dataset consisted of 395 unique patients (mean age 81.5, SD= 6.8). 14.4% of the test set developed clinical AD within five years. On the test set, the model achieved 89% sensitivity (SN), 70% specificity (SP), and an F1 score of 0.87 (Figure 1). This is superior to accelerometric‐only (SN 67%, SP 70%, F1 0.68) and clinical‐only (SN 76%, SP 80%, F1 0.78) models. Model accuracy was similar for patients both with and without mild cognitive impairment at baseline. When the binarized model output was used as a predictor for five‐year AD‐free survival via Cox proportional hazards (Figure 2), it achieved a C‐index of 0.729 [95% CI 0.69 b‐0.77], a hazard ratio of 6.90 [95% CI 4.15‐11.47], and a log‐likelihood ratio of 71.05. Further tuning and validation of the model are underway.ConclusionA deep learning model using wrist accelerometry and easily obtained clinical features shows promise in predicting 5‐year AD outcomes in adults without dementia at baseline.
Towards predicting individual cognitive trajectories in AD using Quantitative Systems Pharmacology
Authors: Schuttel Ivo , Short Shaina M , Geerts Hugo 
Published: January 2025

AbstractBackgroundWhile a number of recent anti‐amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.MethodIn a previously calibrated computational neuroscience model of ADAS‐Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage‐gated Na and K+ channels and synaptic density. The quantitative relationship between amyloid and tau biomarker was derived from a mechanistic QSP model. The effect of CNS active comedications and impact of COMTVal156Met and 5HTT‐rs23352 genotype on relevant neurotransmitter receptors were calculated using affinity data and clinical information.ResultWe used a virtual twin approach to simulate the cognitive trajectory of individual patients from the ADNI database based on their individual baseline comedications, genotypes, amyloid and tau load. Comparison to the actual observed trajectory revealed the importance of common dopaminergic and serotonergic genotypes. We also found that serotonergic pharmacology of comedications could substantially modulate differential cognitive trajectories for the same amount of amyloid increase.ConclusionSuch a predictive platform, once validated can be useful to support clinical trial design, with regard to stratification and protocol amendments and reducing outcome variability by comparing the cognitive trajectory of subjects on active treatment with the same patients in a virtual placebo arm.
Exploring the impact of mindfulness training and a health promotion program on cognitive and mental health of older adults
Authors: Santos Ana Carolina Teixeira , Gomes Leandro , Pereira Diana R , Ribeiro Fabiana , Silva‐Fernandes Anabela , Godinho Catarina , Carvalheiro Joana , Federspiel Carine , Steinmetz Jean‐Paul , Leist Anja K. 
Published: January 2025

AbstractBackgroundThe positive effects of mindfulness‐based stress reduction (MBSR) on cognition, stress relief, and sleep have been well‐documented. However, there is limited research on its potential benefits for older adults, particularly within vulnerable populations such as migrants. This study aimed to compare the impacts of MBSR with a health promotion program in individuals aged ≥55.MethodA monocentric, randomized, double‐blind controlled clinical trial was conducted with 89 participants (≥55 years old), all Portuguese‐speaking immigrants in Luxembourg. They were randomly assigned to a 2‐month group intervention, either MBSR (N = 44) or Health Education Program (HEP, n = 45). Data collection occurred at baseline, end of the intervention, and one to three months post‐intervention. Executive functioning was assessed using the Trail Making Test, Stroop color‐word task, and letter‐number sequencing. Secondary outcomes encompassed general cognitive functioning, cortisol level, heart rate variability, and self‐reported affective and mindfulness states.ResultOf the 125 individuals screened, 89 (mean age: 62.58 years ± 6.08, 63 [70.8%] women) were enrolled, with 75% completing at least one post‐intervention assessment in MBSR and 53% in HEP, included in the modified intention‐to‐treat analysis. The overall dropout rate was 36% and no adverse effects were identified. Time effects were observed in the Letter‐Number Sequencing (β = 0.47, SE = 0.23, t = 2.09, p = 0.04), anxiety (β = ‐1.70, SE = 0.49, t = ‐3.46, p < 0.01), and perceived stress (β = ‐2.17, SE = 0.71, t = ‐3.05, p < 0.01). However, there were no significant group differences or group*time interactions (p > 0.05).ConclusionsBoth interventions demonstrated positive impacts on attention, anxiety, and perceived stress among older migrants, indicating that these group interventions have the potential to improve cognitive and affective indicators irrespective of the intervention content. Future studies could further investigate these findings by incorporating an additional control arm with no social contact to help validate the protective effects of group interventions in older vulnerable populations. Our work underscores the significance of positioning these interventions as potential strategies within the realm of dementia prevention.
Strategies for recruiting diverse young adults into aging research
Authors: Munoz Haydee Izurieta , Casas Antonio , Gaddy Myles , Sanchez Selena Hernandez , Johnson Leigh A. 
Published: January 2025

AbstractBackgroundIn aging research, there is an increasing focus on the decades leading up to changes in cognition. Biomarker studies have suggested that biochemical brain fluctuations can occur up to 20 years prior to clinical symptoms. Including populations of adults who are 20 years away from any cognitive symptomatology in aging research can shed a light on the longitudinal factors involved in brain aging. The aim of this study was to describe and evaluate the methods of recruiting ethnically diverse younger adults (30‐49 years old) into aging research.MethodThe Health & Aging Brain Study‐ Health Disparities (HABS‐HD) study is a community based longitudinal study of cognitive aging in a multiethnic cohort. Participants must undergo an interview, neuropsychological testing, a blood draw, an MRI scan and PET scan of the brain. The study began in 2017, with the goal of enrolling 3000 diverse participants 50 years or older. Thanks to a grant from the National Institute of Aging, the study began enrolling 1500 participants 30‐49 years old in September 2022. The previous outreach strategies focused on older adults had to be modified and updated to cater to the younger group. The outreach team developed, implemented and tracked a variety of strategies from people signing up from the study through enrollment.ResultFrom September 2022 through November 2023, 541 people 30‐49 signed up to be part of the study. 69.7% were female and 30.3% were male, with a mean age of 40 (SD = 5.9). Of those 541 sign ups, 461 participants scheduled an appointment and 332 came in for their study visit (61.4% enrollment rate). The sample included 207 Black/African Americans, 234 Hispanics, 93 Non‐Hispanic Whites and 7 participants of another race. Enrollment data showed that the younger group were recruited mostly through personal referrals (40.1%) and outreach events (38.1%).ConclusionThe study team had to modify approaches to recruitment in order to enroll a younger cohort into the HABS‐HD study, since approaches used previously for older adult were not sufficient. Personal referrals were the biggest drivers of successful enrollment, which suggests that personal trust is crucial in recruiting a novel cohort.
Economic Implications of Dementia in the United States: Assessing the Relationship Between Direct Medical Spending and Informal Care Costs
Authors: Lastuka Amy , Breshock Michael , Dieleman Joseph L 
Published: January 2025

AbstractBackgroundThere are 6.7 million people living with dementia in the United States, and this number is projected to increase as the population ages. The cost of informal care makes up a large proportion of the societal costs of dementia due to the significant care needs associated with the condition.MethodWe combined previously created estimates of direct medical spending attributable to dementia with estimates of informal care costs to arrive at a total societal cost for dementia. Informal care estimates are based on survey data from the Health and Retirement Study, the National Health and Aging Trends Study, and the Behavioral Risk Factor Surveillance System. Both replacement cost and forgone wage cost are estimated for informal care.ResultWe estimated that the annual societal cost attributable to dementia in 2019 was $60,311 (95% uncertainty interval [UI] $56,230–$64,507) per prevalent case when informal case is measured in terms of replacement cost, and $36,245 (95% UI $34,562–$37,960) per prevalent case when informal care cost is measured in terms forgone wages of caregivers. The contribution of informal care to total costs varied substantially by state, ranging from 58% (95% CI 55‐60%) in Connecticut to 84% (95% CI 83‐85%) in New Mexico when measured in terms of replacement cost. When measured in terms of forgone wages, the contribution of informal care ranged from 43% (95% CI 41‐45%) in Connecticut to 69% (95% CI 67‐70%) in Arizona.We found a negative relationship between direct and indirect costs of dementia. When disaggregating based on type of care, we found that this inverse relationship was driven by long‐term care and ambulatory care. The cost of informal care was not correlated with the cost of emergency department care or inpatient care.ConclusionThe inverse relationship between direct and indirect costs of dementia provides suggestive evidence that they act as substitutes. While the substitution between informal care and long‐term care is unsurprising, more research is needed to understand potential mechanisms linking informal care and ambulatory care costs.
Characteristics of heart failure complicated by dementia
Authors: Kokubo Manabu , Shimizu Atsuya , Kamihara Takahiro , Hirashiki Akihiro , Takeda Akinori , Arai Hidenori 
Published: January 2025

AbstractBackgroundWith its rapidly aging population, Japan has been seeing an increase in the concurrent incidence of dementia during heart failure treatment, making disease management difficult. Nevertheless, not much has been uncovered about the actual state of the treatment status and prognosis of heart failure patients with dementia.MethodAt the National Center for Geriatrics and Gerontology, we retrospectively analyzed cases of patients who died of heart failure between 2018 and 2022, who were also complicated with dementia, and whose treatment progress from the initial onset of heart failure to death could be confirmed.ResultOverall, 20 patients satisfied the above criteria. Their mean age at death was 89.4 ± 3.3 years (10 males: 89.3 ± 2.3 years; 10 females: 89.5 ± 3.7 years). The mean duration from the initial onset of heart failure (heart failure stage C) to death was 2.4 ± 3.3 years, with a maximum of approximately 11 years and a minimum of several days.The mean number of hospitalizations during the course of the disease was 2.1 ± 1.4, with the highest number being 6, and 9 patients ending up dying during the first hospitalization. Four patients developed dementia after the onset of heart failure, and their treatment duration tended to be prolonged. Only four patients were institutionalized at the time of the onset of heart failure. The most common underlying disease was hypertension, which was observed in 19 patients. Additionally, atrial fibrillation, chronic kidney disease, valvular heart disease, and ischemic heart disease were noted in 9, 10, 6, and 6 patients, respectively. Regarding the classification of heart failure, 12 patients had HFpEF, and 8 had HFrEFConclusionThe 5‐year survival rate following the initial onset of heart failure is reported to be 75%. However, a poorer prognosis is likely expected if a heart failure patient is complicated with dementia. The possible factors behind this include the onset of the disease upon entering the older age, the status of oral medications, and difficulty in self‐management. A more detailed examination of the actual situation will be required.
The Southern Illinois University Longitudinal Cognitive Aging Study: A Cohort Analysis
Authors: Settelmyer Zachary , Overby Mark S. , Botchway Albert , Scaife Steven , Zec Ronald F. , Ala Thomas A. , Shah Raj C. , Ranjit Eukesh , Hascup Erin R. , Trivedi Mehul A. 
Published: January 2025

AbstractBackgroundThe Southern Illinois University Longitudinal Cognitive Aging Study (SIU LCAS) is a community‐based, longitudinal cohort study initiated in 1984. LCAS was initially designed to improve the sensitivity of neuropsychological testing to diagnose mild cognitive impairment (MCI) and dementia in individuals residing in central and southern Illinois.MethodParticipants are recruited from the community via newspaper advertisement, word‐of‐mouth, and community presentations. Individuals with a family history of Alzheimer’s dementia (AD) are strongly represented in this cohort. Participants must be cognitively normal at baseline and free from any neurological, uncontrolled medical, or psychiatric disease at their first visit. Recruitment is primarily focused on individuals over age 60. Participants complete a neuropsychological test battery assessing all major cognitive domains as well as questionnaires assessing personality, subjective cognitive ability, lifestyle factors, and detailed medical history.ResultThe study has enrolled over 1,600 normal control participants since study inception. 150 original participants continue their participation. The average age at first visit is 66.5 (age range: 20‐95). The majority of participants are female (68.4%) and White/Not Hispanic (97.8%). Most participants (93%) have at least 12 years of education. 95% of the participants remained in the state of Illinois throughout their study participation. 29% of participants come from small or rural towns based on NCES locale boundaries data. 39% of participants reside in disadvantaged communities based on Area Deprivation Index scores of 8‐10. 55.4% of participants completed at least two study visits. 22% participants have completed >10 study visits. 63% of study participants are deceased. Only 26 of the deceased participants were enrolled in the brain donation program (17 with autopsy‐confirmed Alzheimer’s disease). 103 individuals met the diagnostic criteria for MCI or AD at baseline. 87 participants enrolled as controls declined to MCI or AD during their participation. 15 participants developed another neurological condition. An additional 86 participants who discontinued participation were found to have been diagnosed with MCI or dementia after discontinuation based on available medical records.ConclusionCurrent directions involve the recruitment of participants from areas of central and southern Illinois who reside in some of the most disadvantages communities in the United States.
Dual‐task disparities in gait and functional mobility among older adults with a fall‐related mild traumatic brain injury and people living with dementia
Authors: Okrah Albert K , Parada Stephen A , Jirau‐Rosaly Wanda D , Bursey Max , Reynolds Bradford , Ohamadike Chijioke , Jehu Deborah A 
Published: January 2025

AbstractBackgroundMild traumatic brain injury (mTBI) increases dementia risk. Delays in diagnosis are common due to insensitive tools, prolonging symptoms and time to treatment. Dual‐task gait and functional mobility deficits are present post‐mTBI and in people living with dementia (PWD); however, it is unclear whether dual‐tasking can be used as a tool to differentiate between groups. This study aimed to 1) assess whether dual‐task mobility is more sensitive to detect differences between older adults with a mTBI relative to PWD than single‐task mobility; and 2) examine dual‐task cost between groups.Methodn = 3 community‐dwelling older adults with a fall‐related mTBI (Age:68.6 years, Montreal Cognitive Assessment (MOCA) = 23 points, 67% Female) and n = 25 PWD in residential care facilities (Age:82.1 years, MOCA = 10.2 points, 36% Female) wore 6 APDM inertial sensors and completed two usual pace walking trials (single‐task) with or without naming words (dual‐task). Participants also completed two trials of the timed‐up‐and‐go, which involved getting up from a chair, walking 3 m, turning around, walking back, and sitting down (single‐task) with or without completing a category task (dual‐task). Separate repeated measures analyses of variance were conducted for gait and the TUG.ResultThere were no between‐group interactions (p>0.05). There was a Condition by Measure interaction for gait (F(1.13,29.49) = 35.25, p<0.001, ηp
2 = 0.58) and functional mobility (F(1.53,39.89) = 6.0, p<0.01, ηp
2 = 0.19). Dual‐tasking provoked slower gait speed (dual‐task:0.36 m/s; single‐task:0.54 m/s), greater double limb support (dual‐task:38.0%; single‐task:31.8%), lower midswing elevation (dual‐task:0.91cm; single‐task:1.28cm), and shorter stride length (dual‐task:0.55m; single‐task:0.71m;p<0.001) than single‐tasking. The dual‐task TUG provoked longer time to completion (dual‐task:33.2s; single‐task:22.2s), smaller turn angle (dual‐task:120.7°; single‐task:140.2°), and slower turn velocity (dual‐task:80.3m/s; single‐task:94.1m/s) than the single‐task TUG.ConclusionThere were no between‐group differences in single‐ or dual‐task mobility; however, these findings should be interpreted with caution as we have only tested n = 3 participants in the mTBI group, and data collection is ongoing. Both groups experienced some level of cognitive impairment, highlighting that the deficits observed in dual‐ relative to single‐task mobility were likely a manifestation of increased attention demand. Further work is underway to determine whether dual‐tasking may be a sensitive measure to screen and monitor mobility impairments in these populations.
Real‐world effectiveness of anti‐amyloid therapies: the feasibility of obtaining historic controls from large‐scale disease registries
Authors: Jönsson Linus , Winblad Bengt , Wimo Anders , Herring William L 
Published: January 2025

AbstractBackgroundNovel anti‐amyloid therapies (AAT) for Alzheimer’s Disease (AD) have recently been approved in the United States, Japan and China, and are under regulatory review in Europe. Questions remain regarding the long‐term effectiveness and value of these drugs when used in routine clinical practice. Data from follow‐up studies will be important to inform their optimal use, including criteria for treatment initiation, monitoring strategies, stopping rules, pricing and reimbursement considerations. Newly initiated treatment registries will only or mainly enroll patients receiving AAT with no control arm ‐ for comparisons with of health outcomes in untreated patients, external historic control data will be required.MethodWe reviewed the literature to identify disease registries with relevant design and inclusion criteria.Patient‐level data was obtained from two registries deemed to be promising as sources of historic control data: the Swedish Registry for Cognitive Disorders (SveDem) and the National Alzheimer’s Coordinating Centers (NACC). From these registries we selected patients fulfilling key criteria for treatment with AAT and analyzed longitudinal data on relevant endpoints (disease progression, functional status and mortality) using survival analysis methods. Sample size requirements for evaluating the effect of AAT on these endpoints were estimated using the Lachin & Foulkes method assuming a risk ratio of 0.7 with treatment.Result35 disease registries were identified from 15 countries. Many did not include the relevant patient populations, endpoints or had insufficient follow‐up. From SveDem and NACC, 1378 and 7392 patients respectively were included, respectively. The median time to disease progression was 1.9‐3.2 years, time to full‐time care 2.7‐5.3 years, and median overall survival 11.4‐13.6 years. Approximately 248 events would be required to detect a difference in time to event with 80% power. In SveDem, a total number of 2717 disease progression events, 3916 full‐time care events and 842 mortality events were observed.ConclusionFollow‐up studies will be of key importance for confirming the clinical effectiveness and economic value of DMT in routine care. Established registry infrastructures with available historic datasets will play an important role. International collaboration may be needed to achieve sufficient sample size for assessment effects on some endpoints, such as overall survival.