bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of APOE Genotype on Endolysosomal Dynamics in Neurons
Authors: Nyberg Emma MC , Konings Sabine C , Lindblom Nils JN , Klementieva Oxana , Martinsson Isak , Gouras Gunnar K 
Published: December 2023

AbstractBackgroundAPOE genotype is known as the most important genetic risk factor for developing AD. Understanding the cellular differences between the ApoE isoforms will be crucial for understanding the fundamental pathways that are disrupted in AD and potential pathways that can be therapeutically targeted. Accumulating evidence is suggesting that ApoE isoforms influence the endosomal system, one of the earliest sites affected in AD. However, our understanding of how the isoforms affect the endolysosomal pathway is still limited. We aim to understand how ApoE isoforms affect the endosomal pathway, but also understand the dynamics of the system in the context of ageing and activity.MethodTo study cellular changes in neurons we are using primary hippocampal/cortical brain cultures, harvested from ApoE KO mice and targeted replacement mice, expressing human ApoE3 or ApoE4. Neurons in culture have accelerated maturation and with time in culture gradually show signs of age‐like stress. To study ApoE in the context of ageing, mature cultures at 18 days in vitro (DIV18) and more aged cultures at DIV25 were used. To explore how ApoE isoforms adapt to elevated activity DIV18 primary cultures were treated for 48 H with the GABA receptor antagonist bicuculline.ResultOur preliminary data suggests that especially early endosomes are affected in ApoE4 neurons. Interestingly, the appearance of the early endosomes seems to differ depending on both the intracellular localization and time in culture. However, the protein level of the early endosomal marker EEA1 remained unaltered in ApoE4. In addition, preliminary data indicate that ApoE4 has reduced capacity to adjust the endosomal system following 48 hours bicuculline treatment. When studying the trafficking of fluorescently tagged EGF (which has an established endolysosomal route), preliminary results show potential differences between both DIV18 and DIV25 but also between ApoE‐isoforms, suggesting that both time in culture and ApoE isoforms influence endolysosomal trafficking.ConclusionThe endolysosomal pathway is a highly dynamic and important system for all cells, including neurons and is increasingly linked to AD. Our preliminary findings point toward an ApoE isoform effect on endosomal trafficking and that its dynamics might be disrupted by ApoE4.
Resting‐state network connectivity changes in prodromal stage of Alzheimer’s disease
Authors: Mateu Karen Aguilar , Laguardia Ana María Castro , Guerra Jorge Llibre 
Published: December 2023

AbstractBackgroundAlzheimer Disease (AD), the most common type of dementia, is accompanied by a generalized loss of neurons and cause severe changes in brain’s structure and function. Mild Cognitive Impairment is associated with a higher risk of developing dementia. This clinical classification is particularly relevant because each subtype is linked to a presumed etiology, with the amnestic subtypes (aMCI) considered as a prodromal form of AD (Petersen et al., 2009, 2014). Resting state fMRI functional connectivity (FCrs‐fMRI) analysis is broadly used to detect brain network differences in neurodegenerative diseases such as AD.MethodForty‐five participants were evaluated: patients with aMCI (n = 17), patients with dementia due to AD (n = 14) and healthy controls (HC) (n = 14). All participants received an extensive neuropsychological battery and brain MRI scanning. Resting state functional scans consisted of 240 T2*‐weighted echo planar imaging volumes (repetition time 3000 ms; echo time 60 ms; ip angle 90°; 32 axial slices; matrix 64×64; voxel size 3.3×3.4×4 mm). Additionally, a high‐resolution T1‐weighted magnetization prepared rapid acquisition gradient echo image was acquired. Data analyses were performed using the Functional Connectivity Toolbox (CONN) for Matlab (https://www.nitrc.org/frs/) to identify large‐scale patterns of temporal signal‐intensity coherence, interpreted as functional connectivity (Beckmann et al., 2005). Regions of interests (ROIs) analysis was performed for each participants and among group. Spatial maps of the group independent component analysis were used in a linear model t against each individual fMRI data set.ResultThe Default Mode Network (DMN) showed two regions of lower functional connectivity (FC) in AD when comparing with HC within the precuneus (p<0.001 uncorrected). No regions of FC changes were found in the DMN when comparing aMCI with HC or AD.ConclusionThe changes in FC rsfMRI in adults with AD are specifically related to regions of the DMN.
Brain Healthy Soul Food Diet Intervention Among Older African Americans
Authors: Shaw Ashley R. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) poses a major public health crisis, especially among African Americans who are disproportionally burdened by AD. Emerging evidence suggests that up to half of AD cases are a result of modifiable cardiovascular (CV) or metabolic risk factors related to poor diet such as elevated blood pressure, arterial stiffness, obesity, and diabetes, all of which disproportionately affect African Americans. Given the high prevalence of CV related risk factors in the African American community, prevention strategies are critical for reducing the disproportionate impact of AD among African Americans.MethodWe conducted a single arm 12‐week pilot in 2 waves (n = 20 African Americans) to assess feasibility and acceptability of an adapted brain‐healthy soul food diet intervention (MIND+SOUL) as measured by recruitment rates, retention rates, adherence, and satisfaction. The intervention encompassed skill building cooking classes, health coaching, and weekly groceries. We also evaluated preliminary efficacy of the MIND+SOUL diet intervention on CV risk and nutritional health status as measured by body composition, blood pressure, cholesterol, NHANES diet screening questionnaire, and beta carotene spectrophotometer. Lastly, we assessed change in cognition as assessed by the NIH Toolbox (NIH‐TB domains: memory, language, reading, vocabulary, processing speed, and executive function).ResultA total of 20 African Americans participated in the study with a retention rate of 90%. Most participants perceived the MIND+SOUL diet as feasible to follow (88.9%) and perceived the MIND+SOUL diet as effective in improving their overall health (77.8%). The median acceptability score was 67 out of 100 in which participants suggested modifications to the health coaching design and dissemination. Additionally, participated completed baseline and 12‐week CV, nutritional health status, and cognitive assessments.ConclusionFindings from this study indicate that older African Americans have a high interest in culturally tailored diets. Additionally, findings from this study will inform the development of a full‐scale randomized control trial that will test the efficacy of the MIND+SOUL intervention among older African Americans across a larger geographical area.
Alzheimer’s disease risk genes modulate interferon‐responsive microglia
Authors: McQuade Amanda , Castillo Vincent Cele , Drager Nina , Kampmann Martin 
Published: December 2023

AbstractBackgroundHuman genetic studies and quantitative trait loci (eQTL) analyses have implicated microglia, the innate immune cells of the brain, as critical players in Alzheimer’s disease (AD). In response, the field has focused on defining microglial transcriptional states across many models of neurodegeneration. Integrating these studies, we find several microglial activation states commonly enriched in AD. These include Disease Associated Microglia, Antigen‐Presenting Microglia, and Interferon‐Responsive Microglia. To truly make use of this data, we now must move towards understanding the functional consequence of these microglial activation states and uncovering the mechanisms that drive changes in cell states during disease.MethodTo determine regulators of the interferon‐responsive microglial activation state, we performed a functional genomic screen using CRISPR interference (CRISPRi). To avoid bottlenecking of CRISPR guide RNAs and accommodate the large numbers of cells needed for screening, we implemented a novel transcription‐factor driven approach to differentiate iPSC‐derived microglia. After differentiation, microglia harboring individual gene knockdowns were primed with type I interferon and screened on expression of IFIT1, a key marker of the interferon‐responsive microglial state.ResultThese experiments have uncovered both canonical regulators of interferon signaling as well as novel regulators of the interferon‐responsive microglial state. Furthermore, several known AD risk genes were shown to inhibit microglial entry into this state, suggesting a potential mechanism whereby these nodes may influence disease risk.ConclusionRecent transcriptomic studies have uncovered significant heterogeneity of microglial states including the discovery of several disease associated states. However, it remains unclear whether these states represent beneficial, disease‐fighting functions or detrimental, disease‐promoting functions. Gaining the ability to selectively control entry into specific microglial states will allow novel investigations into how these specific microglial states interact with and guide disease trajectories.
Sex/Gender Differences in the Diagnosis of Pain by Cognitive Status
Authors: Milani Sadaf Arefi , Fang Kuo Yong‐ , Downer Brian , Berenson Abbey , Doulatram Gulshan , Raji Mukaila 
Published: December 2023

AbstractBackgroundUnderdiagnosis of pain is common in women and in those with Alzheimer’s disease and related dementias (ADRD). However, sex/gender differences in pain interference, defined as pain that interferes with daily activities, have not been examined along the cognitive spectrum. We assess sex/gender differences in odds of physician‐diagnosed and self‐reported pain, by cognitive status: normal, cognitively impaired but not dementia (CIND), and dementia.MethodsWe will use data from the 2006 to 2018 waves of the Health and Retirement Study (HRS) linked to Medicare Claims. We will include participants aged 66 and older with at least one year of continued enrollment in Medicare. Our pain diagnosis measure will incorporate self‐reported pain interference, herein referred to as pain, with pain diagnosis in a three‐level variable: no pain, undiagnosed pain (self‐reported only), and diagnosed pain. Cognitive status (normal cognition, CIND, dementia) was measured using the Telephone Interview for Cognitive Status. We will use generalized estimating equation models to calculate gender disparities in the odds of pain diagnosis, by cognitive status. Here we present preliminary results, using cross‐sectional data from the 2018 HRS (n = 7,588) to examine self‐reported pain by cognitive status. We include descriptive statistics and logistic regression models, adjusted for age, race/ethnicity, years of education, marital status, depression, diabetes, arthritis, and obesity.ResultsWomen more often reported pain compared to men for those with normal cognition (women: 27.7%, men: 18.7%; p<0.001) and CIND (women: 32.6%, men: 18.9%; p<0.001). Among those with dementia, 29.9% of women and 22.7% of men reported pain (p = 0.108). For those with normal cognition and CIND, women had higher odds of reporting pain compared to men [normal cognition odds ratio (OR): 1.34, 95% confidence interval (CI): 1.16, 1.55); CIND OR: 1.84 95% CI: 1.38. 2.47]. However, no sex/gender disparity is observed among those with dementia (95% CI: 1.13, 95% CI: 0.66, 1.94).ConclusionsIn our preliminary analysis we found that the sex/gender disparity in self‐reported pain interference is not present among those with dementia. The final version of this work will incorporate the Medicare data from 2006 to 2018 so that we can assess sex/gender differences in clinician‐documented pain diagnosis.
Meta‐analysis of NIH Alzheimer’s Disease‐Related Dementias (ADRD) programs responsive to the National Plan to Address Alzheimer’s Disease (AD)
Authors: McCartney Amber J , Shukla Arvind , Yin Xiling , Dodson Sara , Bryant Erin , Corriveau Roderick A 
Published: December 2023

AbstractBackgroundAD/ADRD diseases currently impact more than 6 million people in the US. Rare forms of AD/ADRD are caused directly and unambiguously by genetic mutations. However, most AD/ADRD burden is complex in etiology and thought to result from an interplay among multiple incompletely understood genetic, biochemical, lifestyle, environmental and psychosocial risk factors. Moreover, risk factors interact with other health factors to impact AD/ADRD outcomes. For example, while the most common dementia diagnosis is AD, research over the past decade revealed most people with a diagnosis of AD have multiple brain pathologies, other comorbidities, and many people diagnosed with clinical AD do not have AD pathology at all. This new knowledge highlights the importance of better understanding dementia syndromes, and the relationships among them, to increase chances of developing effective interventions. The NINDS partners with the NIA, the NIH lead for AD/ADRD, in the NIH response to the National Plan. NINDS leads ADRD including frontotemporal dementia (FTD), Lewy body dementias (LBD), vascular contributions to cognitive impairment and dementia (VCID) and multiple etiology dementias (MED). This project aims to evaluate NIH and the ADRD field’s responsiveness to ADRD research milestones from triennial NINDS ADRD Summits by mapping NIH‐funded research activities to ADRD milestones.MethodThe approach used text‐based analysis/mining of grant titles, abstracts, and specific aims to map awards and activities to ADRD milestones. Mappings were vetted by expert concurrence. The ongoing study includes new or competitively renewed NIH ADRD awards starting from fiscal year 2017. Findings help NIH to better understand the state of the field, identify research gaps and opportunities for future efforts, and enable public communication of research activities with an accurate, accessible, compact, and updatable data visualizations.ResultResults indicate the approach is feasible, and importantly the field and NIH have largely been responsive to the ADRD milestones in the National Plan to Address AD.ConclusionThe analysis points to several cross‐cutting ADRD research areas that may benefit from increased attention going forward, including health equity, the multiple etiology hypothesis of common dementias, emerging risk factors for common dementias (e.g. COVID‐19, TBI, and TDP‐43 proteinopathy), and clinical trials.
Look AHEAD Sleep: Study Design and Baseline Characteristics
Authors: Hayden Kathleen M. , Neiberg Rebecca H. , Bertisch Suzanne , Chen Haiying , Culkin Margaret C. , Dennis Stephen , Ding Jingzhong , Garcia Katelyn R , Rapp Stephen R. , Redline Susan , Blanco Jeannette Rosales , Sachs Bonnie C. , Sanderlin Ashley H. , St‐Onge Marie‐Pierre , Espeland Mark A. , Wagenknecht Lynne E , Spira Adam P. 
Published: December 2023

AbstractBackgroundOlder adults with obesity (body mass index [BMI] ≥30 kg/m2) and type‐2 diabetes (T2D) have increased risks for mild cognitive impairment (MCI) and dementia. Sleep‐disordered breathing (SDB) is common in older adults and those with T2D and obesity, and has been linked to increased risk of Alzheimer’s disease (AD) and Alzheimer’s disease‐related dementias (ADRD). SDB may represent a unique and modifiable pathway that elevates the risk of cognitive decline among patients with T2D and obesity. Yet, few studies have examined associations between SDB and cognitive outcomes among persons with T2D and obesity. Addressing this gap is critical as the prevalence of metabolic disorders is increasing, placing a growing population at risk for MCI, and AD/ADRD. Look AHEAD Sleep (LA‐Sleep) was designed to study associations of SDB and circadian rhythms with cognitive function in older adults with a history of these conditions. Here, we report initial baseline characteristics of LA‐Sleep cohort.MethodParticipants enrolled in Look AHEAD Aging (LA‐A), a continuation of the Look AHEAD cohort study, were eligible to participate in LA‐Sleep. Participants completed cognitive assessments and were randomized to have a sleep assessment in either Year 1 (2022‐2023) or 2 (2023‐2024). Year 1 participants completed sleep questionnaires and received in‐home sleep assessment devices (WatchPAT and ActiGraph) and a sleep diary by mail.ResultOf 1,522 who consented to LA‐A, 952 agreed to LA‐Sleep and to date, 161 have provided year 1 WatchPAT (n = 161) or Actigraph (n = 107) data. There were more females (55.3%) than males; the average (±SD) age was 76.1±5.4 y; average BMI was 34.3±7.0; and 10.6% of the sample was Non‐Hispanic Black, 6.2% Hispanic, and 76.4% Non‐Hispanic White. Most had more than a high school education (90.1%). Of those with obesity in 2018‐2020, 20.0% had severe SDB (apnea hypopnea index ≥30). Overall mean actigraphic‐estimated sleep duration was 7.1±1.4 hours, sleep efficiency (total sleep time/time in bed) was 87.0%, and wake‐after‐sleep‐onset was 62.5±31.0 minutes/night.ConclusionAmong an older adult cohort with T2D and overweight or obesity, a high proportion of participants have severe SDB and high levels of sleep fragmentation, placing them at increased risk for cognitive impairment.
A Living Lab in the Quebec’s Homes for older adults with a neurocognitive disorder: aiming to improve the personalization of long‐term care and the self‐determination of residents and their relatives
Authors: Hudon Carol , Ribon‐Demars Alexandra , Batcho Charles , Gaied Nouha Ben , Blanchette Andreanne , Bolduc Francois , Charest Caroline , Cote Nancy , Collomb‐d'Eyrames Olivier , Duchesne Simon , Feillou Isabelle , Fortin Elise , Gagnon Caroline , Giguère Andrée , Giguère Anik , Guénette Line , Hardy Marie‐Soleil , Laberge Maude , Labonte Marie‐Eve , Langevin Louise , Lapierre Judith , Macoir Joel , McFadyen Bradford James , Methot Pierre‐Olivier , Monetta Laura , Morisset Anne‐Sophie , Peters Valerie , Raymond Emilie , Routier Francois , Singamalum Sonia , Tanguay Pascal , Voyer Phillippe 
Published: December 2023

AbstractBackgroundThe “ Quebec’s Homes for Older Adults with a Neurocognitive Disorder ” (QHOA) model aims to improve the quality of residential and long‐term care environments for people losing their autonomy. Considering the major paradigm shift behind the QHOA philosophy, it seemed timely to co‐construct a Living Lab‐type structural organisation whose main mission will be to contribute to the sustainability of the new model.ObjectivesSince 2021, we have been co‐constructing links between scientists, decision‐makers, staff (carers, cooks, housekeepers, etc.), QHOA stakeholders and, above all, the community and its seniors. Our structure is a Living Lab and the main objective is to cyclically and participatively co‐construct a set of solutions applicable to QHOAs. Our work will encourage the design and development of sustainable solutions by considering human (e.g., self‐determination, personalization of care), environmental (e.g., layout and design, camouflage strategies), technological (e.g., sensors, cameras, connected watches and scales, artificial intelligence, software for care and medication), work organization, and continuous training of stakeholders.ResultsThe co‐construction process involved more than 40 researchers, clinicians, decision‐makers, or stakeholders. We have all been able to delineate the structure of the Living Lab and how knowledge will be disseminated, rallied, and promoted. This presentation will resume the main steps (including successes and challenges) of our work.ImplicationsA Living Lab is a place for collaboration, exchange, and co‐creation. The actors in the field have the most relevant knowledge of the living context in which the projects will be deployed. Our intersectoral team (20 fields of expertise) will provide the scientific knowledge to ensure the sustainability and ongoing development of the QHOA model.
Gender differences in the mediational pathway between trauma, depression and subjective cognitive decline
Authors: Brown Monique J , Esiaka Darlingtina , Viswanathan Jaya 
Published: December 2023

AbstractBackgroundAdverse childhood experiences (ACEs) have been linked to subjective cognitive decline (SCD) in later life, which may be a precursor for Alzheimer’s disease. However, studies examining the potential mechanisms between ACEs and SCD as well as the differential role that gender might play in these pathways are lacking. The aim of this study was to assess how gender influences the association between ACEs, depression and SCD.MethodData were obtained from 14,630 respondents (6,254 men and 8,376 women) from the 2021 US Behavioral Risk Factor Surveillance System survey. Trauma was operationalized as the experience of ACEs. A depression categorization was based on respondents’ self‐report of ever being informed of having a depressive disorder. SCD was operationalized as respondents reporting having experienced increasing confusion or memory loss in the past 12 months. Crude and adjusted stratified path analyses using PROC CALIS were conducted to determine the direct and indirect associations between ACEs, depression, and SCD overall and by gender.ResultPreliminary analyses show that in the overall study population, respondents who reported experiencing ACEs were more likely to report depression (B = 0.165; p<0.0001) and those who reported a depression diagnosis were more likely to report SCD (B = 0.191; p<0.0001) in the past year. There was also a direct positive association between ACEs and SCD (B = 0.085, p<0.0001) where respondents with a history of ACEs were more likely to report SCD. Depression mediated the association between ACEs and SCD (B = 0.032; p<0.0001) Stratified path analyses showed similar findings for men and women where depression was a mediator in the relationship between ACEs and SCD (men: B = 0.025; p<0.0001; and women: B = 0.036; p<0.0001).ConclusionDepression mediated the association between ACEs and SCD in the overall population, and among men and women. There was no moderating role of gender in the mediational pathway between ACEs, depression and SCD. Further analyses will be conducted to elucidate the interaction effects in these data. Future studies should assess the moderating role of gender in alternative mediational pathways such as examining substance use, and PTSD as potential mediators in the relationship between ACEs and SCD.