bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer’s Disease
Authors: Yau Wai‐Ying Wendy , Kirn Dylan , Rabin Jennifer S , Properzi Michael J , Schultz Aaron P , Rentz Dorene M. , Johnson Keith A , Sperling Reisa A , Chhatwal Jasmeer P. 
Published: January 2025

AbstractBackgroundPhysically inactivity is associated with increased risk of dementia including Alzheimer’s disease (AD). Prior work from the Harvard Aging Brain Study (HABS) suggests that lower baseline physical activity in cognitively unimpaired individuals with elevated amyloid burden is associated with faster prospective cognitive decline. However, whether this detrimental effect on cognition in preclinical AD is mediated by accelerated tau pathology remains unclear.MethodWe examined 293 baseline cognitively unimpaired older adults from HABS (Table 1). Baseline physical activity (mean steps per day) was measured using a waistband‐mounted pedometer (HJ‐720ITC; Omron Healthcare) worn over 7 consecutive days during waking hours. Using linear mixed effects models, we examined the interactive effects of baseline physical activity and amyloid PET burden (Pittsburgh Compound‐B) on longitudinal cognitive decline (Preclinical Alzheimer Cognitive Composite‐5 [PACC5]), adjusting for age, sex and education (APOE not significant). In a subset of 169 participants, we examined the interactive effects on longitudinal tau pathology (Flortaucipir PET) in 36 whole‐brain FreeSurfer cortical and limbic ROIs (FDR‐correction). We further investigated if the physical activity effects on PACC5 decline in preclinical AD are mediated by changes in tau.ResultIn a larger sample of HABS participants with up to 13 years of cognitive follow‐up, we replicated the significant interaction between lower physical activity and elevated amyloid burden on faster prospective cognitive decline (β = 0.09, t = 3.42, p<0.001; Figure 1A). We further demonstrated a novel interactive effect on tau pathology, where lower physical activity was associated with accelerated amyloid‐related tau accumulation in inferior temporal (ITC) and middle temporal (MTC) cortices (ITC: β = ‐0.10, t = ‐3.36, FDR‐p = 0.02; MTC: β = ‐0.09, t = ‐3.27, FDR‐p = 0.02; Figure 1B). Importantly, moderated mediation analyses revealed that accelerated tau accumulation fully mediated the effects of lower physical activity on faster cognitive decline in the setting of elevated amyloid (p<0.001, 100% mediated; Figure 2).ConclusionOur findings provide strong support for promoting physical activity as a lifestyle intervention, in conjunction with anti‐amyloid therapy, to slow the onset and/or progression of early neocortical tau pathology and cognitive decline in preclinical AD.
Self‐disclosure about dementia on social media: toward evidence‐informed guidance
Authors: English Mahala G , Tam Mallorie T , Hrincu Viorica , Robillard Julie M. 
Published: January 2025

AbstractBackgroundSocial media platforms are increasingly used by people living with dementia and their care partners to seek information and advice, share personal stories, raise awareness, and offer support to others. Engagement with social media is often accompanied by a personal disclosure of a dementia diagnosis or identification as a care partner, but the impact of this disclosure remains unknown. Social media engagement can be beneficial by facilitating peer‐interactions and social support; however experts have raised concerns about the potential for exposure to misinformation and stigma as a result of self‐disclosure. As the popularity of self‐disclosure on social media increases, balancing these risks and benefits is critical to promote healthy and safe social media use for people living with dementia and their care partners. The goal of this project is to deliver an evidence‐based resource to support decision‐making around social media use in dementia.MethodAs a first step toward addressing this goal, the current project aims to identify the motivations and impact of self‐disclosure on social media. Posts related to self‐disclosure were retrieved from Facebook groups and pages over a six‐month period for analysis. Automated and manual sentiment‐ and model‐based interaction analyses were carried out on the data to characterize posts based on their 1) primary motivation for self‐disclosure, 2) polarity, 3) bids for action, and 4) anonymity of the poster.ResultPreliminary findings reveal information‐ and support‐seeking as the most common motivations for self‐disclosure, highlighting the importance of guidance on identifying misinformation and engaging in healthy peer support.ConclusionThis work will help empower the dementia community to access support and information safely in the increasingly popular social media spaces to enhance peer supports and access to high‐quality resources.
24 hour behaviors and dementia risk
Authors: Yiallourou Stephanie , Cribb Lachlan , Campbell‐Brown Beaudan , Brakenridge Christian , Baril Andree‐Ann , Pase Matthew P. 
Published: January 2025

AbstractBackgroundShort sleep duration, low physical activity and high sedentary time are associated with higher dementia risk. To date, previous studies have considered these behaviors in isolation, and not as inter‐related behaviors part of the 24‐h day. Compositional data analysis (CoDA) treats these behaviors as inter‐related within a constrained 24hrs. This allows for estimating the association of reallocating time from one behavior to another on health outcomes whilst adjusting for the remaining behaviors.Using CoDA, we estimated the association of substituting sleep duration for daytime behaviors (sedentary, light and moderate‐to‐vigorous physical activity [MVPA]) on dementia risk in those with short (<6h) and normal sleep (≥6h).Method88,654 dementia‐free participants (63 years (Q1, Q3: 56, 68); 56% female) from the UK Biobank completed 7‐day/night accelerometry (Axivity AX3). Incident all‐cause dementia was ascertained based on hospital records, death records, and primary care. CoDA isometric log‐ratios were used to examine the association between 24‐h use of time and dementia risk. Risk ratios for the associations between reallocating up to 1h sleep time to time in other activities and all‐cause dementia were estimated.ResultThere were 484 incident all‐cause dementia cases over a median follow‐up of 7.2 years. Figure 1 presents the associations between discrete time‐use substitutions and dementia risk.In persons with normal sleep duration, replacing light activity with sleep time was associated with a lowering of dementia risk (Fig. 1c). Conversely, replacing MVPA with sleep time was associated with the largest increase in dementia risk (Fig. 1e).In persons with short sleep duration, replacing inactivity and light activity with sleep time was associated with a lowering of dementia risk (Fig. 1b‐d). In contrast to those with normal sleep duration, replacing sleep with MVPA did not lower risk of dementia in short sleepers (Fig. 1f).ConclusionThe way in which 24‐h time use, comprised of sedentary behavior, light activity, MVPA, and sleep, is balanced may have implications for dementia risk. In short sleepers, prioritising 1h of sleep over sedentary or light activity could be a beneficial for dementia prevention. These findings have the potential to inform more targeted and precise dementia risk prevention guidelines.
The TIE‐93 : a cross‐cultural facial emotion recognition in French and North African Alzheimer’s dementia patients
Authors: Bourdage Renelle , Franzen Sanne , Papma Janne M. , Palisson Juliette , Joy Charlotte , Garcin Béatrice , Narme Pauline 
Published: January 2025

AbstractBackgroundFacial emotion recognition testing in Alzheimer’s disease (AD) patients has been identified as key for early detection and as a marker for disease progression. Emotion recognition remains one of the most difficult domains to assess in culturally diverse populations due to a lack of culturally adapted tools. This study assessed the feasibility of a cross‐cultural test for emotion recognition, the TIE‐93, in French and North African populations living in France.MethodForty‐six patients with AD and 148 healthy controls (aged 60 years+), from French and North African backgrounds (mostly Morocco and Algeria), were included in the study. The TIE‐93 is composed of eight panels with photos of actors displaying six basic emotions (happiness, anger, disgust, fear, sadness and neutral). The participant is given a daily life scenario eliciting an emotion (e.g., he is sad because is mother is very sick) and are asked to identify which of the six facial expressions displayed matches this scenario.ResultFrench controls (n = 82) scored higher (41 ± 5.2) than North African controls (n = 66, 36 ± 7.2) on the TIE‐93, t(146) = ‐5.64, p<.001. With French controls stopping education later in age (18 ± 4) than North African controls (13 ± 7), regression analyses were conducted to assess the contribution of education and country of origin on performance. A significant regression was found for education R2 = .19, F(1,146) = 34.86, p<.001, and country of origin R2 = .24, F(2, 145) = 23.45, p<.001. A group of education matched controls with a high education for French (n = 33) and North African (n = 33) participants were compared on test performance; no significant differences were found, t(146) = ‐1.53, p = .12. Due to small sample sizes, performance in only French AD patients (n = 37) were compared to French controls, with AD patients scoring significantly lower (31 ± 7), t(117) = ‐4.2, p<.001.ConclusionThe TIE‐93 seems promising for assessing facial emotion recognition in AD patients, demonstrating a decline in facial emotion recognition consistent with previous research literature.
AD pathology in LBD – Implications for Clinical Trials
Authors: Patel Bhavana 
Published: January 2025

AbstractAlzheimer’s disease (AD) is a common copathology in Lewy body dementia (LBD). The presence of AD is associated with a distinct clinical presentation, faster progression, and shorter survival in LBD. However, the relationship between‐alpha synuclein and AD remains incompletely understood. The objective of this session is to discuss the challenges that this poses to clinical translation of approved therapies for AD and LBD‐specific clinical trial design.First, we will discuss the impact of the significant advances in the treatment of AD that have occurred in the past years. Specifically, the publication of evidence supporting the use of anti‐amyloid monoclonal antibodies as disease‐modifying therapies for AD leading to the approval of three different therapies by the Food and Drug Administration (FDA). Currently, Lewy body dementias are excluded from the appropriate use recommendations for Aducanumab and not mentioned in the Lecanemab appropriate use recommendations. We will discuss how the current data may translate to its application in LBD and what needs to be considered when designing and interpreting trials for anti‐amyloid therapies in LBD.Second, we will discuss how the presence of AD in LBD can also affect the effect of an intervention, even if it is not directed to AD pathology. In a recent Phase II study of neflamapimod, individuals with DLB and AD biomarkers were also less responsive to the experimental therapy. This warrants consideration of AD biomarkers in clinical trial design which will be discussed during the session.Finally, we will comment on how the presence of copathology, specifically LBD, can also affect current AD‐specific clinical trials.
Effect of a hearing intervention on 3‐year cognitive change is greater among older adults at high risk of cognitive decline: ACHIEVE randomized trial
Authors: Pike James Russell , Huang Alison R , Reed Nicholas S , Burgard Sheila , Chisolm Theresa , Couper David , Deal Jennifer A. , Glynn Nancy W. , Gravens‐Mueller Lisa , Hayden Kathleen M. , Mitchell Christine , Pankow James , Sanchez Victoria A , Sullivan Kevin J. , Tan Nasya , Coresh Josef , Lin Frank R ,   ACHIEVE Collaborative Research Group
Published: January 2025

AbstractBackgroundThe Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.gov Identifier: NCT03243422) randomized trial investigated the effect of hearing intervention versus health education control on 3‐year cognitive change among dementia‐free older adults with untreated hearing loss. Participants were recruited from the Atherosclerosis Risk in Communities (ARIC) study (n = 238) or de novo from the community (n = 739). The hearing intervention slowed cognitive decline by 48% in ARIC participants, but not in healthy de novo volunteers. A possible explanation for this difference is that the cognitive benefits of hearing intervention could only be observed for individuals at increased risk for cognitive decline.MethodTo evaluate whether risk of cognitive decline moderated the effect of a hearing intervention, we used a sample of dementia‐free ARIC participants (N = 2,692) who did not participate in ACHIEVE to develop a model that explained 80.7% of the variance in cognitive decline over a 6‐year period (Figure 1). The model included baseline measures of age, hearing loss, systolic blood pressure, body mass index, physical activity, physical function, depression, and cognitive test performance. The model was applied to baseline measures of ACHIEVE participants (N = 977) to calculate their predicted risk of cognitive decline. The covariate‐adjusted, intention‐to‐treat effect of the hearing intervention on 3‐year cognitive change was examined in a mixed effects model that included random treatment assignment and predicted risk of cognitive decline. A three‐way interaction between time, randomization, and predicted risk of cognitive decline was tested.ResultAt the ACHIEVE baseline (2018‐19), 523 participants were women (53.5%), 112 participants were Black (11.5%), the mean (SD) age was 76.8 (4.0) years old (Table 1), and the 3‐year predicted risk of cognitive decline had a median (IQI) of ‐0.288 (‐0.372, ‐0.207). A nonlinear interaction (Figure 2) between time, predicted risk of cognitive decline, and the hearing intervention was observed in the top quartile of risk (p = .01). Among participants in the top quartile of risk, cognitive decline in the hearing intervention group was 58.1% (95% CI 31.4%‐90.9%) slower than the control group.ConclusionThe effect of a hearing intervention on 3‐year cognitive change was greatest among individuals at high risk of cognitive decline.
Post‐COVID Cognitive impairment in a large hospital‐based multi‐ethnic sample during the COVID‐19 pandemic
Authors: Neal Reem M. , Yang zhiyi , Hajjar Ihab 
Published: January 2025

AbstractBackgroundCOVID‐19 has been associated with developing cognitive impairment. Individuals with cognitive impairment have a higher likelihood of progressing into dementia. Furthermore, studies have suggested that COVID‐19 is associated with an increased risk of developing Alzheimer’s disease (HR 2.03). Despite the increasing number of individuals developing post‐COVID cognitive impairment, the risk factors remain unclear.MethodWe used the electronic health record data on 32,018 patients with at least one COVID‐19 infection from 2020‐2022. We defined cognitive events based on ICD 10 for memory loss, mild cognitive impairment, dementia, or any neurocognitive disorders. We looked at the temporal relation between these events and the COVID‐19 events and classified patients as either with or without cognitive impairment and whether it was an incident (i.e. only after COVID without any pre‐COVID cognitive impairment or pre‐existing cognitive impairment). We then explored potential correlates with COVID‐related cognitive impairments. We also evaluated the effect of race and sex on the possible risk factors for developing post‐COVID cognitive impairment. We used Multivariable logistic regression to determine the significance of associations.ResultIn this study of 32018 patients with a COVID infection, and a mean age of 60, we found that the prevalence and incidence of post‐COVID cognitive impairment were higher in African American patients vs. White patients (prevalence 25% vs 23% incidence: 15% vs 13%) and male vs. female 39% vs. 33% patients. We also found a greater risk for post‐COVID cognitive impairment to be associated with delirium, recurrent COVID infection, kidney disease, and cardiovascular disorders, OR increased by 4.7, 2.4, 2.1 & 2.3 respectively (all P<0.0001). In contrast, we found that obesity, Remdesivir use, and prevalent psychiatric, and respiratory disorders decreased the odds of having post‐COVID cognitive impairment (OR 0.84, 0.83, 0.64, and 0.86 respectively) (all P<0.0001). The risk of cognitive diagnosis post‐COVID significantly differed by race with AA males having the highest risk. (all P<0.0001).ConclusionOur study shows post‐COVID cognitive impairment is common with the top risk factors being AA race, recurrent COVID infections, and cardiovascular disorders. Future studies should investigate the role these risk factors play and their contribution to the mechanisms underlying post‐COVID cognitive impairment.
Targeting Tauopathy with a Novel Conformational Specific Intrabody
Authors: Tsaka Grigoria , Michiels Emiel , Vandenberghe Rik , Thal Dietmar Rudolf , Rousseau Frederic , Schymkowitz Joost 
Published: January 2025

AbstractBackgroundPathological tau accumulation is the primary constituent of neurofibrillary tangles and other tau aggregates seen in various neurodegenerative diseases collectively known as tauopathies. Recently, immunotherapeutic strategies focused on tau have shown promise in reducing tauopathy in both cellular and animal models.MethodWe previously used humanized yeast models to purify recombinant hyper‐phosphorylated human Tau for mouse immunizations and the isolation of a high‐affinity anti‐Tau monoclonal antibody (mAb) with enhanced diagnostic and prognostic capacities. Although conventional immunotherapeutic approaches targeting tau can influence tau pathogenesis, the majority of pathological tau remains in the cytosol of cells, not typically accessible to an extracellular antibody. Therefore, based on the in‐house mAb we designed a single‐chain fragment variable (ScFv), named 16B12, that is abundantly expressed in cellulo.ResultOur results demonstrate that the expression of 16B12 significantly diminishes the presence of Tau aggregates in cells exposed to brain‐derived seeds obtained from Tau PS19 mice at different ages, as well as from individuals with Alzheimer’s disease at varying stages and patients with different Tauopathies (CBD, PSP, PiD). This reduction is higher compared to a known tau fibrillar core‐targeting nanobody or an off‐target ScFv.ConclusionOur conformational specific intrabody eliminates tauopathy in cellulo and our goal is to further explore the therapeutic capacities of the AAV‐delivered ScFv in delaying or eliminating tauopathy in human Tau transgenic mice.
Usability analysis of a web laboratory for cognitive stimulation with acquired brain injury users
Authors: Moreno Maria Celeste López , Urriategui Karen D , Fernández‐Zaionz Axel , Sarmiento Elsa Araceli Revollo , Vivas Leticia 
Published: January 2025

AbstractBackgroundIn 2020, we developed LABPSI, a cognitive stimulation web lab. Usability analysis in MCI and healthy participants have already been studied, and currently, we performed it with acquired brain injuries (ABI) participants, as they can rehabilitate their cognitive symptoms and prevent the progression to dementia. Usability can be considered the ease of use of a certain product for a specific aim by a particular population. The study’s primary objective is to assess LABPSI’s long‐term usability in ABI participants.MethodOur sample comprised 12 ABI participants with focal and diffuse lesions (33.3% stroke, 41.7% TBI, 25% others) in the subacute phase. All participants were in treatment during data collection. With a mean age of 51.08 (SD = 19.96, range: 24‐77 years), we recorded their educational level (average: 9.91 years) and technological expertise (mean: 80.41) regarding the maximum questionnaire score of 136 (Range = 49‐109; SD = 19.29), it reflects a moderate to high level of technology familiarity. LABPSI underwent a long‐term assessment using a pre‐experimental design with a single group, including pre‐test, guided training, and post‐test phases. Objective measures evaluated effectiveness and efficiency of a specific task on the LABPSI, which was divided into: initial task phase (steps from the beginning of LABPSI to the start exercises) and exercise resolution phase. The effectiveness was operationalized through steps achieved and the number of errors, while the efficiency considers the time spent to achieve the task and steps achieved in 3 minutes.ResultA Wilcoxon Test indicated significant results in 5 out of 7 measures. In the initial task phase, time spent (p = .380) and errors (p = .463) were not significant, but steps achieved and steps achieved in 3 minutes were (p<.05). For the exercise resolution phase, all objective metrics (steps achieved, errors, and time spent) showed significant values (p<.05) indicating better performance in the post‐test.ConclusionOur findings suggest that LABPSI exhibits promise as a rehabilitative tool for individuals with ABI, featuring a user‐friendly interface tailored to their needs. Exploring the long‐term usability of LABPSI enhances our understanding and contributes to knowledge on cognitive rehabilitation strategies, aiding in collaborative efforts to prevent dementia.