bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring users' perspectives of the Driving and Dementia Roadmap
Authors: Naglie Gary , Stasiulis Elaine , Rapoport Mark J. ,   CCNA Driving Cessation Team Co‐Investigators and CCNA Study Group
Published: January 2025

Background

Since October, 2022 the Driving and Dementia Roadmap (DDR) (www.drivinganddementia.ca) – an online resource to support people with dementia (PWD), family/friend carers (FCs) and healthcare providers (HCPs) as they navigate the challenges of driving cessation – has been accessed by over 34,000 users. To understand the DDR’s impact we are conducting on‐going surveys to explore users’ perspectives of the DDR.

Method

As users exit the DDR, they are invited, via pop‐up message, to participate in an online survey about their experiences with the DDR, including their perceived new knowledge and confidence gained due to using the DDR and their satisfaction with it. Descriptive statistics were conducted via the REDCap platform.

Result

To date, 81 DDR users have participated in the survey (17 PWD, 33 FCs and 31 HCPs). Topics rated the highest as “new knowledge gained” included: for PWD, “recognizing unsafe driving” (17.6%) and “getting around without driving” (17.6%); for FCs, “recognizing unsafe driving” (59.4%) and “learning about licensing and reporting” (59.4%); and for HCPs, “providing support after driving cessation” (61.3%) and “having discussions and managing emotions” (45.2%). With regards to increases in confidence reported as “somewhat” to “much more confident”, the highest rated topics included: for PWD, “making the decision to stop driving” (47.1%) and “recognizing unsafe driving” (41.2%); for FCs, “making the decision to stop driving” (71.9%) and “initiating conversations about driving cessation” (68.8%); and for HCPs, “managing the emotional impact” (71.1%) and “having conversations about driving cessation” (67.7%). Satisfaction levels by participants across all DDR characteristics were rated as “satisfied” to “very satisfied” by at least 47% of PWD, 87% of FCs and 80% by HCPs, with “trustworthiness of the information” rated the highest by all three groups (PWD: 75.1%; FCs: 93.8%; HCPs: 87.1%).

Conclusion

Early results indicate that a majority of users were satisfied with the DDR and using the DDR led to gains in new knowledge and increased confidence in managing aspects of driving cessation for all 3 groups, but least so for PWD. The next step will involve in‐depth interviews with participants to better understand the user experience and the relatively lower ratings among PWD.
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

Background

Physically 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.

Method

We 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.

Result

In 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).

Conclusion

Our 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

Background

Social 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.

Method

As 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.

Result

Preliminary 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.

Conclusion

This 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

Background

Short 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).

Method

88,654 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.

Result

There 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).

Conclusion

The 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

Background

Facial 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.

Method

Forty‐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.

Result

French 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.

Conclusion

The 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

Alzheimer’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

Background

The 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.

Method

To 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.

Result

At 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.

Conclusion

The 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

Background

COVID‐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.

Method

We 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.

Result

In 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).

Conclusion

Our 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

Background

Pathological 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.

Method

We 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.

Result

Our 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.

Conclusion

Our 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

Background

In 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.

Method

Our 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.

Result

A 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.

Conclusion

Our 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.
Enhancing participation in research for Asian American, Native Hawaiian, and Pacific Islander Populations: An update on the CARE Registry
Authors: Park Van Ta , Tsoh Janice Y. , Meyer Oanh L. , Nam Bora , Tzuang Marian , Vuong Quyen , Hinton Ladson , Gallagher‐Thompson Dolores , Kanaya Alka M. , Huang Daren , Fara‐On Gabriel , Grill Joshua D
Published: January 2025

Background

Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations are underrepresented in Alzheimer’s disease and related dementias (ADRD) research, despite being the fastest growing racial group in the United States. The Collaborative Approach for AANHPI Research and Education (CARE) registry aims to create a sustainable research recruitment source to address this need.

Method

Participants can enroll online, by phone, or in‐person by completing an enrollment survey in English, Chinese (Simplified/Traditional), Hindi, Korean, Samoan, or Vietnamese. Guided by a Community Advisory Board, CARE is strategically promoted as a registry that supports “health research across the lifespan,” focusing on ADRD, dementia caregiving, and aging‐related topics. CARE regularly holds Brain Trust Meetings to promote CARE in the research community, and researchers can request support for their study recruitment.

Result

Between October 2020 and January 2024, 10,133 total AANHPI adults enrolled in the CARE registry. Participants’ mean age is 51.8 years (Standard Deviation (SD) = 17.9), including 2,450 middle‐aged (50‐64 years old) and 3,373 older (≥65 years old) participants. About 14% (n = 1,402) of the participants reported having ADRD symptoms. Among the 1,072 caregivers, 40.4% reported caring for someone with ADRD. Most participants who had self‐reported ADRD symptoms (96.4%) and caregivers (76.5%) were foreign‐born with 61.7% speaking limited English. The major cultural groups among ADRD caregivers were Chinese (33.2%), Vietnamese (26.5%), Korean (11.3%), Asian Indian (7.6%), and Japanese (8.8%). Of the 98 recruitment referral requests received, 64 (65.3%) were aging‐related, including 49 (50%) ADRD or ADRD‐caregiving studies. CARE shared data with 51 studies and over 5,500 CARE participants have been referred to at least one study from January 2021 to January 2024.

Conclusion

CARE has successfully recruited over 10,000 AANHPI participants who are interested in health research participation. Participants from several AANHPI groups were limited (e.g., Filipino, Asian Indian, Native Hawaiians/Pacific Islanders), however, we anticipate future growth following language expansions and targeted outreach efforts. The registry stands as a valuable recruitment source and fosters meaningful and necessary engagement of AANHPI representation in ADRD‐related research.
Sex‐specific differences in the association between regional adiposity, cognition, and brain pathology in older adults with Type II Diabetes
Authors: Boccara Ethel , Golan Sapir , Ganmore Ithamar , Ravona‐Springer Ramit , Livny Abigail , Ben‐Meir Mery , Azuri Yossi , Weller Aron , Beeri Michal S
Published: January 2025

Background

While body mass index (BMI) is widely used to gauge overall adiposity, its accuracy in older age has yielded inconsistent findings. Moreover, BMI does not account for variations in regional fat distribution, which may differ between sexes. This study aims to investigate whether regional adiposity plays a distinct role in impacting cognition and the volumes of AD‐related brain regions in older adults with T2D enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study.

Methods

Regional adiposity was measured by abdominal MRI in 103 participants (33.3% women), including hepatic and pancreatic fat, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Participants underwent neuropsychological assessment including global cognition, episodic memory (EP), working memory (WM), executive function (EF) and language. A subsample of 52 participants (36% women), underwent brain MRI assessing hippocampus, inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]. Partial correlations examined associations of regional adiposity with cognition and brain volumes adjusting for age, sex, education, BMI (and intracranial volume for volumetric MRI).

Results

In the whole sample, higher pancreatic fat approached significance with lower global cognition (r = ‐286, p = 0.054). No associations were found for specific cognitive domains. In men, but not in women, high pancreatic fat was associated with lower global cognition (Men: r = ‐0.336; p = 0.042; Women: r = ‐0.299; p = 0.565), and lower episodic memory (Men: r = ‐0.345; p = 0.036; Women: r = ‐0.064; p = 0.787). In women, but not in men, high hepatic fat was associated with lower working memory (Men: r = 0.035; p = 0.835; Women: r = ‐0.486; p = 0.022). In the whole sample, no associations were found between regional adiposity and brain volumes. Whereas, in men, higher hepatic fat was associated with smaller MFG (Men: r = ‐0.492, p = 0.013; Women: r = 0.021, p = 0.949) and with smaller SFG (Men: r = ‐0.407, p = 0.043; Women: r = ‐0.097, p = 0.765).

Conclusion

In older adults with T2D, who are at high ADRD risk, distinct regional fat depots have different associations with brain and cognition in men and women. Those differential sex effects are consistent with those of our recent publication on middle‐aged high ADRD risk sample. These findings highlight the need to account for sex differences when investigating the role of adiposity in brain aging.
Montreal Cognitive Assessment in Spanish‐speaking countries in Latin America and the Caribbean: A Systematic Review
Authors: Bustamante‐Paytan Diego , Diaz‐Mejia Angie , Saenz‐Orihuela Gianinna L. , Moncada‐Mapelli Enrique , Salazar Leslie , Montesinos Rosa , de la Colina Adrian Noriega , Custodio Nilton
Published: January 2025

Background

The prevalence of dementia in Low and Middle‐Income Countries (LMICs), particularly in Latin America and the Caribbean (LAC), is projected to triple by 2050. The Montreal Cognitive Assessment (MoCA) is widely used for cognitive evaluation, but its uniform application in LAC is questionable, especially due to cultural and linguistic diversity of the Spanish‐speaking LAC countries.

Method

A systematic literature search was conducted across seven databases, supplemented by a comprehensive review using Google Scholar to identify relevant grey literature. Studies validating or culturally adapting the MoCA, conducted in Spanish‐speaking institutions in the LAC region, with available psychometric measures and comparisons to gold‐standard diagnostic criteria, were considered for inclusion. Fourteen studies were identified that validated the MoCA in LAC. Twelve studies meeting inclusion criteria were analyzed using the Manchester Cultural Adaptation Questionnaire and Manchester Translation Reporting Questionnaire. The adaptation process and psychometric reports were thoroughly assessed.

Result

Among all reviewed articles, 12 detailed MoCA validation across LAC populations (Fig. 1). Only two reported significant adaptations to the original version, with one study providing a detailed cultural rationale (Table 1). The adaptation process assessment revealed limited reporting on translation steps (Table 2). Concerning the psychometric report, internal consistency, criterion validity, and construct validity were the most frequently addressed aspects across all studies. In all studies where low‐educated populations were evaluated, educational level was reported to bias the results. We identified a lack of standardized criteria for definition of illiteracy across the studies.

Conclusion

This systematic review identified limited reporting on translation steps emphasizes the need for standardized processes in future adaptations. We recommend cultural awareness during MoCA administration in the region. Future studies must address appropriate cut‐off scores based on educational level adjustments in LAC countries.
The ADNI4 Digital Study: A novel approach to recruitment, screening, and assessment of participants for AD clinical research
Authors: Nosheny Rachel L. , Miller Melanie J. , Albala Bruce , Conti Catherine C. , Flenniken Derek , Fockler Juliet , Kwang Winnie , Truran‐Sacrey Diana , Diaz Adam , Ashford Miriam T. , Skirrow Caroline , Weston Jack , Fristed Emil , Farias Sarah Tomaszewski , Korecka Magdalena , Yang Wan , Lee Eddie B , Aisen Paul S. S. , Petersen Ronald C. , Shaw Leslie M. , Okonkwo Ozioma C , Mindt Monica Rivera , Weiner Michael S. W.
Published: January 2025

Background

Scalable, efficient methods are needed to enroll diverse populations of older adults into AD observational studies and clinical trials. We evaluated preliminary feasibility of a novel, digital, culturally informed approach to recruit and screen participants for the Alzheimer’s Disease Neuroimaging Initiative (ADNI4).

Methods

Digital advertising tailored towards Black/African American and Latinx older adults residing near six clinical ADNI sites directed potential participants to a recruitment website (Figure 1). They completed digital surveys of demographics, ADNI exclusion criteria, memory concerns and changes, self‐report cognitive impairment, and the Everyday Cognition Scale (ECog)‐12 item. Participants also completed Novoic Storyteller, a self‐administered speech‐based cognitive test. Digital assessment results were used to prioritize those from minoritized ethnocultural groups, with low educational attainment, and possible Mild Cognitive Impairment (MCI) for remote blood draw at local Quest phlebotomy centers to obtain AD plasma biomarkers. Completion rates and digital assessment performance were compared between minoritized and non‐minoritized groups.

Results

Of 989 participants recruited from digital advertising efforts who provided contact information, 230 (23%) signed consent, and 183 (19%) completed at least one remote assessment (Table 1). 45% were from minoritized ethnocultural groups, 4% had ≤12 years of education, and 53% had evidence of possible MCI from digital assessments. 34 (19%) were referred to the plasma biomarker study, of which 21% completed blood draw. Compared to non‐minoritized participants, minoritized participants were less likely to report a diagnosed cognitive impairment or a family history of AD, less likely to have ECog scores indicative of MCI, and less likely to have a study partner. Minoritized participants had lower ECog and Novoic Storyteller completion rates.

Conclusion

Recruitment and assessment of a diverse cohort of older adults, including those with possible cognitive impairment, is feasible using culturally informed digital advertising. Improving study engagement and achieving educational diversity are key challenges. This approach is now being scaled up to facilitate recruitment into in‐clinic ADNI4, with the goal of enrolling 500 new participants: >50% from minoritized groups, 40% with MCI, and 80% amyloid positive across diagnostic groups. This approach can be adapted to facilitate recruitment and longitudinal assessment in other AD studies and trials.
LXR Agonists as Therapeutic Agents for Myelin Repair: Exploring the Molecular Mechanisms of Oligodendrocyte Remyelination and Cholesterol Synthesis
Authors: Tamhankar Sampada P , Steinke Ian , Singh Meenakshi , Amin Raj
Published: January 2025

Background

Alzheimer’s disease (AD) is characterized by hallmark amyloid plaques and neurofibrillary tangles as well as by a significant loss of myelin in the cerebral cortex and other brain regions, which contributes to neurodegeneration and cognitive decline. Remyelination, of the myelin sheath by oligodendrocytes, is a process that may be impaired in neurodegenerative diseases. Depending on the severity of the disease, there occurs loss or partial damage of the myelin sheath surrounding the neuron leading to memory deficits. Liver X Receptors (LXRs), as regulators of cholesterol homeostasis, present an intriguing target for therapeutic intervention, as cholesterol is a vital component of myelin. The proposed research seeks to investigate the potential of LXR agonists to stimulate myelin production in oligodendrocytes, thereby promoting remyelination in the AD brain. This study will assess the capacity of LXR‐induced remyelination to alleviate cognitive deficits associated with demyelination in AD pathology.

Method

Wild type and 5XFAD mice were used for in‐vivo and MO3.13‐ human hybrid cell lines that express phenotypic characteristics of primary oligodendrocyte were used for in vitro studies. A Potent LXR agonist (GW3965) was used to study the remyelination properties The cell lysate was then resolved using SDS PAGE – western blot analysis.

Result

5XFAD mice show comparatively lower expression of pre‐ and mature oligodendrocyte biomarkers compared to wild types. As per the literature, M03.13 has genes for myelination but does not express any associated protein. We have observed that the MO3.13 cell line expresses the pre‐myelination markers but lacks the mature myelination marker. Surprisingly, treatment with GW3965 induces myelination markers expression.

Conclusion

The current study provides evidence that LXR agonists can be used to enhance the myelination properties within the oligodendrocyte. Further work will focus on the application of LXR agonists in Frontal temporal dementia and ALS‐related neurodegenerative disease.
An Interprofessional Team for Disease Modifying Therapy in Alzheimer’s Disease Implementation
Authors: Turk Katherine W. , Knobel Mark D , Nothern Alexandra , Friedman Garrett , Noah Hannah , Campbell Brendan , Anderson Diana , Charidimou Andreas , Mills Andrew , Coronel Vanessa , Pierre Nacha , Reynolds Beverly , Wagner Caroline , Varga Leanne , Roefaro John , Triantafylidis Laura , Budson Andrew E.
Published: January 2025

Background

Lecanemab and other new amyloid‐targeting immunotherapies for Alzheimer’s disease show great promise but, may also pose significant risk for patients. To facilitate the implementation and monitoring of lecanemab infusions at our tertiary medical center, we convened an interprofessional team. The team created a number of resources including patient handouts and medical documentation templates as well as systems and processes. As the first VA in the country, and one of the first clinical settings in the country overall to begin Lecanemab infusions, it is our intent to widely share the resources and processes developed as well as share initial clinical experiences.

Methods

An interprofessional team at VA Boston Healthcare System (VABHS) (Disease Modifying Therapy in Alzheimer’s Disease, DMTAD group): behavioral neurologology attendinds and fellows, neuropsychiatry fellows, geriatricians, neuroradiologist, infusion nurses, geriatric clinical pharmacists, and a physician assistant was assembled and began meeting weekly for one hour. The team’s initial objective was to streamline processes and systems for initiation of lecanemab treatment as well as assessment, review, and monitoring of patients from memory disorders and geriatrics clinics for potential treatment based on VA criteria for use. Responsibilities of the group also included placing medication orders, routinely reviewing imaging, and monitoring for any medication‐related side effects and adverse reactions patients may have experienced in the preceding week.

Results and Clinical Experiences to Date: Since infusions began in October 2023 16 patients have completed full screening evaluation for including amyloid PET, APOE testing, MRI brain within 3 months, and baseline lab work.

8 were ineligible for Lecanemab: blood thinners (6), APOE 4 homozygosity (2).

20 additional patients undergoing screening work up for eligibility currently.

8 patients are actively completing infusions: 4 have experienced mild to moderate side effects including chills and flu like sensations after infusions 1 or 2.

4 have tolerated without side effects. No patients have experienced ARIA to date.

Conclusions

An interprofessional team is effective at screening and monitoring potential Lecanemab patients at a tertiary medical center and overall screened patients are safely tolerating infusions in a real world setting.
Antisense oligonucleotide‐based α‐synuclein targeting as a disease‐modifying treatment for Dementia with Lewy bodies (DLB) disease
Authors: Ahammad Rijwan Uddin , Spencer Brian , Leitao Andre D. G. , Rissman Robert A.
Published: January 2025

Background

Dementia with Lewy bodies (DLB) is characterized by the accumulation of α‐synuclein (α‐syn) as well as Alzheimer’s disease (AD) pathology, which includes the accumulation of amyloid beta (Aß) in plaques and phosphorylated tau in tangles, leading to neurodegeneration, cognitive loss and dementia. In DLB and other synucleinopathies, α‐syn oligomers and proto‐fibrils are thought to be mechanistically linked to the pathogenic neurodegenerative process. AD and related disorders (ADRD) are leading causes of dementia in the aging population and although new approaches are being tested, to date no disease‐modifying therapies are available.

Method

We utilized 2’‐OMe modified ASO‐syn or ASO‐scrambled, conjugated with ApoB11, which can cross the blood‐brain barrier. ApoB11:2’‐OMe ASO peptides were systematically delivered to DLB tg/non‐tg mice to evaluated pharmacokinetics, pharmacodynamics and toxicology profile and determine its effects on α‐syn and neurodegeneration using qPCR, immunohistochemistry and Western blot.

Result

We found that ApoB11:2’‐OMe ASO targeted to α‐syn was well tolerated and safe in DLB tg mice without evidence of toxicity and it was successfully delivered to the mice brain. In addition, treatment with ApoB11:2’‐OMe ASO targeted to α‐syn significantly reduced α‐syn aggregates in brains of DLB tg mice. Our ongoing experiment shows changes in neuronal survival, motor performance and cognition with the treatment.

Conclusion

Collectively, our findings suggest that the reduction of α‐syn through the use of systemically‐delivered ApoB11:ASO α‐syn is a safe disease‐modifying treatment for DLB and may hold promise as a future therapeutic for other synucleinopathies.
GEAR 2.0 ‐ Emergency Care Practices
Authors: Dresden Scott M
Published: January 2025

Persons living with dementia (PLWD) are twice as likely to use the emergency department (ED) and 1.5 times more likely to have an avoidable ED visit than elders without dementia. PLWD have greater comorbidity, incur higher charges, are admitted to hospitals at higher rates, return to EDs at higher rates, and have higher mortality after an ED visit than patients without dementia. When in the ED, they often struggle with the loud, bright, fast‐paced setting and may not be able to give a complete medical history. Additionally, PLWD have different emergency care needs than other patients in the emergency department that may go unrecognized.

Though routine care in the ED is not well suited for PLWD, many experimental changes to components of ED care have been studied for PLWD including comprehensive geriatric assessment, dedicated ED unit, partnering with care partners, optimal pain assessment, fall prevention, delirium screening, admission to hospital at home, palliative care in the ED, and changes to the ED physical environment. This session will review the literature of current and ED care practices for PLWD dementia detection approaches and discuss top research questions generated by the patients, care partners and members of the trans‐disciplinary GEAR ED Care Practices Work Group.
Brain Functional Flexibility and its Relationship to the Preclinical Stage of Alzheimer’s Disease
Authors: Javanray Mohammadali , St‐Onge Frederic , Bellec Pierre , Misic Bratislav , Soucy Jean‐Paul , Villeneuve Sylvia ,   PEREVNT‐AD Research Group
Published: January 2025

Background

Characterizing pathological and functional features of the preclinical stage of Alzheimer’s Disease (AD) is essential as Amyloid beta (Aβ) and tau, the pathological hallmarks of AD, start to accumulate years prior to the onset of clinical symptoms. Whether Aβ and/or tau are related to the brain’s ability to functionally reconfigure in time (functional flexibility) remains unclear despite its important role in behavior and cognition.

Method

We included 233 cognitively unimpaired individuals with family history of AD from the PREVENT‐AD cohort who underwent both Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI). We computed the element‐wise product of the BOLD fMRI timeseries of the 400 Schaefer atlas nodes as co‐fluctuation matrices for the scan duration (all TRs). We then calculated the variabilities of the obtained co‐fluctuations at the whole brain and network level (DMN and limbic as early susceptible networks in AD) and used these measures of variability as a proxy of functional flexibility. We also computed the average of the obtained co‐fluctuation matrices, which mathematically corresponds to the Pearson correlation of the nodal timeseries pairs and used this as our marker of static functional connectivity (sFC). We then assessed the relationship between functional flexibility and sFC with the level of Aβ (global index) and tau (temporal meta‐ROIs), using those, both as continuous and dichotomized variables (Figure 1). Two thresholds were used for Aβ, one associated with low Aβ accumulation (centiloid of 18) and the other with significant Aβ burden (centiloid of 40).

Result

No association was found between AD pathology and functional flexibility or sFC using AD pathology as continuous or dichotomized variables (Figure 2 and 3). However, the maximum range of functional flexibility values in individuals with significant Aβ burden and high tau was about half the one found in individuals with low or no pathology, a result that was particularly striking with tau.

Conclusion

The absence of group difference suggests that functional flexibility cannot be used as a proxy of AD. While individuals with AD pathology have a low range of functional flexibility values, low values are also frequent in individuals with no pathology.