bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining Etiologic Diagnoses in Patients with Rapidly Progressive Dementia
Authors: Day Gregory S , Tipton Philip W , Lazar Evelyn , Martens Yuka A , Dunham S Richard , Geschwind Michael D , Bu Guojun , Morris John C. , Graff‐Radford Neill R. 
Published: December 2022

AbstractBackgroundOverlap in the presenting clinical features and test results in patients with rapidly progressive dementia (RPD) confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. There is a need to improve diagnostic accuracy in patients with RPD, with particular emphasis on identifying patients with potentially treatment‐responsive causes of RPD early in the symptomatic course.MethodPatients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at Washington University (Saint Louis, MO; 2016–2019) and Mayo Clinic (Jacksonville, FL; 2020–2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of widely accessible diagnostic testing and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.Result160 patients with RPD were assessed, with average age‐at‐symptom onset 60.0±15.9 years; 50% were female. Diagnostic inter‐rater reliability (91% agreement; Cohen’s κ = 0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%—i.e., frontotemporal dementia, Lewy body dementia, vascular cognitive impairment), Creutzfeldt‐Jakob disease (15%), and other causes (15%—e.g., neurosarcoid, metabolic disruptions, neoplastic disease). The average age of patients with potentially treatable causes (AE and selected “other” causes; 54.4±18.2) was younger than those with neurodegenerative dementing illnesses (67.3±9.5) or CJD (67.4±7.9; p<0.001). Patients with potentially treatable causes were more likely to present with altered level of consciousness and seizures (p<0.05). CSF pleocytosis (>5 WBC/hpf) was more common in AE patients (p<0.05).ConclusionEtiologic diagnoses can be reliably established in RPD patients using available clinical data. Treatment‐responsive causes of RPD are common warranting consideration, particularly in younger patients with altered consciousness, seizures, and CSF pleocytosis.
Factors associated with Alzheimer’s disease patients’ caregiving status and family caregivingburden in China
Authors: Leng Fangda , Li Yuxian , Sun Wei , Wang Huali , Jin Haiqiang , Sun Yongan 
Published: December 2022

AbstractBackgroundThe increasing prevalence of Alzheimer’s disease (AD) has emerged as a major challenge worldwide. China as the most populous country in the globe is amid rapid aging of its population, highlighting the need for appropriate social and medical policies to meet the challenge. The current study aims to provide understanding of the current status of caring given to AD patients in China and the underlying factors with a large multicenter cross‐sectional observational approach.MethodA total of 1675 patients with probable AD from 30 provincial regions of mainland China were enrolled in the current study from August 2019 to December 2019. We analyzed the caregiving status and its relationship with family burden and various socioeconomical and medical factors.Result90.87% of the patients enrolled adopted family care. The choice of caregiving method was influenced by factors including age (>80 years old, OR 0.648; 95% CI, 0.427–0.983), overall family burden (high, OR 0.574; 95% CI, 0.0.373–0.884),patients’ income (OR 0.511; 95% CI, 0.330–0.789) and self‐care ability (OR 0.329; 95% CI, 0.183–0.588).ConclusionFamily care is the primary method of care for AD patients in China and the institutional care system for AD patients is still underprepared in China.
Applying Variational Autoencoder to Explore Changes in Clock Drawing With Hip Fracture Surgery
Authors: Chapin Benjamin Albert , Bandyopadhyay Sabyasachi , Rodriguez Katie , Amini Shawna , Radhakrishnan Nila , Tighe Patrick , Rashidi Parisa , Price Catherine C. 
Published: December 2022

AbstractBackgroundOlder adults with acute hip fractures are particularly vulnerable to delirium and postoperative cognitive decline. Hospital staff, however, do not screen preoperative cognition or systematically monitor for delirium in these at‐risk individuals. Using the clock drawing test (CDT) our team demonstrated the potential for semi‐supervised deep learning using Variational Autoencoder (VAE) to extract clock drawing anomalies predictive of dementia (Bandyopadhyay, in review). We applied the VAE technique to assess preoperative to postoperative changes in CDTs in patients with acute hip fractures.MethodsPost‐injury, pre‐operative hip fracture patients completed screening including the CDT to command and copy, and a baseline delirium assessment with the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU). Postoperatively, delirium was assessed twice daily. Post‐surgery CDTs were collected after two consecutive negative CAM‐ICUs. A VAE with two latent dimensions was trained using 13,580 unlabeled clocks in an unsupervised manner to create a parsimonious 2D latent space to encode the constructional aspects of the CDT. This latent space was operationalized using a k‐Nearest Neighbor Classifier on a classification dataset consisting of 71 Dementia and 80 Control samples using 3‐fold cross validation. This separated the latent space into the “Red” and “Blue” areas corresponding to “Dementia” and “Control” groups, respectively. We projected the pre and postoperative hip fracture dataset CDTs onto this latent space to investigate changes in CDT relative constructional features post‐surgery for those with and without postoperative delirium.Result27 participants completed our study (age 82.96 ± 9.28; education 13.19 ± 2.90; 85% female). 2 were delirious preoperatively and excluded from analysis, and 4 developed delirium postoperatively (16%). All preoperative command and copy clocks were in the “Dementia” region of the VAE latent space. Copy, but not command clocks moved further into the “Dementia” region. Error type changed in the post‐operative command condition to resemble the copy condition more closely. Trends suggest preoperative copy clock performance may predict delirium risk after surgery.ConclusionSemi‐supervised deep learning with VAE applied to the CDT, particularly the copy condition, shows promise for automated preoperative cognitive screening and postoperative monitoring in at‐risk hip fracture patients. Future studies are needed with larger participant samples.
Developing an Ethnographic Community‐Based Participatory Research Dementia Study with Diverse Indigenous Populations: Indigenous Cultural understandings of Alzheimer’s disease and related dementias – Research and Engagement (ICARE) project
Authors: Blind Melissa J , Warry Wayne , Lambrou Nickolas H. , Pitawanakwat Karen , Ketcher Dana , Pederson Collette , Johnson January , Hill Annamarie , Dertinger Melinda , Koski Jessica , Trudeau Rhonda , Strong Lois , Summers Marlene , Martin Wesley , Lewis Jordan P , Zuelsdorff Megan , Gleason Carey E. , Jacklin Kristen 
Published: December 2022

AbstractBackgroundDementia diagnoses have been increasing in Indigenous populations for over a decade and have now surpassed rates in non‐Indigenous populations in both Canada and the U.S. Prevalence rates of Alzheimer’s Disease and Related Dementias (ADRD) are approximately 3 times higher in Indigenous populations compared to White populations, with a 10‐year earlier onset . The ICARE project (NIH –5R56‐AG‐62307‐2) qualitatively explores the impact of ADRD in Indigenous populations across four diverse sites in Canada and the United States.MethodWe used a community‐based participatory research (CBPR) approach and a two‐eyed seeing framework to establish research partnerships with four Indigenous communities/regions: 7 Anishinaabe First Nations on Manitoulin Island, Ontario Canada; Red Lake Tribal Nation, Minnesota; Grand Portage Tribal Nation, MN; and the Oneida Nation, Wisconsin. The community engagement strategy supported the infrastructure needed to conduct dementia research in a culturally safe and appropriate way that respects Tribal Sovereignty.ResultIndigenous community‐based researchers were hired at each site and each underwent research training designed by the ICARE team. With guidance from local leadership, we established 8–12‐member community advisory groups at each site to serve as partners to guide the research. We collected preliminary ethnographic data on social determinants of health, demographics, community health, aging and dementia specific services. We demonstrated feasibility with pilot data collection of key informant interviews with Traditional Knowledge Keepers, Administrators, and Providers (n = 54) and sequential focus groups with local health care staff and formal caregivers that work with Indigenous older adults (n = 17).ConclusionNIH/NIA R56 funding resulted in the establishment of the community‐based infrastructure to support on‐going ADRD research in the four diverse communities. We demonstrated the feasibility of supporting community‐engaged dementia research partnerships with Indigenous communities who have differing cultural, political and historical contexts. This foundation is supporting the expansion of ICARE into a 5‐year ethnographic research study aimed at creating a foundational ethnographic database of AI/FN lived experience of ADRD across the disease trajectory that can be examined to inform the creation of culturally appropriate and safe approaches to improve dementia diagnostics, care, and outreach (NIH‐R01‐AG‐62307‐2).
Impact of α‐synuclein RNA interference on Neuropathological and Clinical Phenotypes in a mouse model of Alzheimer’s Disease
Authors: Leitao Andre D. G. , Spencer Brian , Wu Chengbiao , Conroy Abigail , Amalraj Jessica N , Mante Michael N , Masliah Eliezer , Rissman Robert A. 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by the pathologic accumulation of beta amyloid (Aβ), Tau and α‐synuclein (α‐syn). The role of α‐synuclein has been extensively studied in Parkinson’s disease, but less so in AD. Recent studies have shown that α‐syn may also play a role in AD and its downregulation could be protective against the toxic effects of Aβ accumulation. First, we hypothesized that selectively knocking down α‐syn improves the neuropathological, biochemical, and cognitive findings in AD. Second, we tested whether α‐syn ablation could enhance AD treatments with donepezil (pro‐cholinergic) and memantine (glutamate antagonist), which are currently ineffective at slowing progression of disease.MethodPSAPP transgenic mice were used to model AD and knockdown of a‐syn was performed by RNA interference. 43 non‐transgenic and 33 PSAPP mice were used in this study. We have selectively knocked‐down α‐syn by two differentmethodsa) first, by stereotaxic bilateral injection of either LV‐shRNA (pan) α‐syn or LV‐shRNA‐luc (control) into the hippocampus and striatum; b) second, by intraperitoneal injection of a complex of ApoB11 and shRNA‐α‐syn, which was previously shown to cross the BBB. Water maze and open field testing were used to measure cognitive deficits. Biochemistry and immunohistochemistry were performed on each hemibrain.ResultWe have successfully utilized these two strategies to down‐regulate α‐syn as shown by lower levels of α‐syn through biochemistry and immunohistochemistry. Importantly, this correlates with a significant reduction in the number of Aβ plaques and tau peptides, suggesting the overlap between Aβ, tau and α‐syn in pathology. Other findings include a reduction in Iba1 staining in mice injected with LV‐shRNA‐α‐syn suggesting involvement of microglia in pathology. Open field testing indicates that α‐synuclein reduction could restore context dependent memory. Moreover, injection of LV‐shRNA‐α‐syn into the hippocampus of mice treated with memantine rescues cognitive deficits to a non‐disease level, as shown by all variables analyzed during water maze trials with an invisible platform (time, entrances and passes in correct zone).ConclusionOverall, this study provides evidence that α‐synuclein knock‐down improves some of the neuropathological and cognitive deficits and could be of therapeutic value in AD, especially when combined with a glutamate antagonist.
The California Face‐Name Associative Memory Exam (C‐FNAME)
Authors: Hall Kathleen , Williams Garrett , Geraci Kristin , Blank Michael , Baldo Juliana , Schendel Krista , Lwi Sandy J. , Chok Jas M. , Herron Tim , Wyma‐Hughes John , Woods David L. 
Published: December 2022

AbstractBackgroundThe Face‐Name Associative Memory Exam (FNAME) is a sensitive measure of associative memory and age‐related cognitive decline, with FNAME scores declining in parallel with increasing amyloid and tau burden in preclinical Alzheimer’s disease (Rentz et al., 2011). Here we describe the California FNAME (C‐FNAME), a fully automated, brief (8.8 min) computerized test designed for at‐home administration under telemedical supervision.MethodPARTICIPANTS. The C‐FNAME was remotely administered to 435 healthy adults (42.8% female, M = 64.8, ±14.7) in their homes via tablet computer. Participants underwent two C‐FNAME test sessions on successive days.TECHNOLOGY. C‐FNAME administration was automated, with instructions delivered using text‐to‐speech and responses scored with automatic speech recognition. Examiners monitored participant performance via video and audio feeds using a web‐browser interface that displayed recall scores in real time.TASK. Participants saw 6 faces with associated first names, last names, and occupations (encoding). Faces were presented individually, and participants repeated the names and occupations before the next face appeared. After each encoding trial, participants were asked to recall the associations when presented with the face alone (Figure 1a and 1b). After 30 minutes, participants saw the faces again one at a time and repeated the recall portion of the task (delayed recall).ResultThe C‐FNAME showed excellent test‐retest reliability (r = 0.83 for total recall scores, r = 0.82 for delayed recall scores). Multiple regression analysis revealed highly significant effects of age (Figure 2), education, gender, and vocabulary on total recall (p < 0.001 for all comparisons), with these variables aggregately accounting for 28.2% of variance. Performance significantly improved by 1.23 standard deviations on repeated testing (p< 0.001). As in previous FNAME studies (Papp et al., 2014), participants recalled occupations more accurately than names (Figure 3).ConclusionAt‐home computerized administration of the C‐FNAME demonstrated excellent psychometric properties and produced results similar to those obtained with FNAME assessments administered in the laboratory. The design of the C‐FNAME allows for rapid, remote administration and scoring, which encourages the participation of populations that may be sometimes excluded from research protocols in laboratory settings.
Chemotherapy as a risk factor for Alzheimer’s disease
Authors: Escarcega Rocio Diaz , Patil Abhijeet A , Manchon Jose Felix Moruno , Urayama Akihiko , Dabaghian Yuri A. , Morales Rodrigo , McCullough Louise D. , Tsvetkov Andrey S. 
Published: December 2022

AbstractBackgroundCognitive impairments may occur in cancer patients and survivors during or after chemotherapy. Cognitive deficits associated with neurotoxicity (chemobrain) can be subtle or disabling and frequently include disturbances in memory, attention, executive function, and processing speed. Cognitive impairments may go away soon after chemotherapy is over or may persist for years and yet, there is a paucity of effective treatments. Research has shown that chemotherapy drugs such as doxorubicin promote neurotoxicity and cognitive disturbances. Critically, some studies demonstrated that dementia occurs more commonly in cancer patients who had chemotherapy treatment compared to individuals never exposed to chemotherapy. Understanding whether and how chemotherapy may promote dementia later in life is needed.MethodTo establish new insights into chemotherapy‐induced cognitive impairments, we use wild‐type and Tg2576 mice (a model of Alzheimer’s disease (AD)) treated with Doxil, a liposomal form of doxorubicin. Mice are injected intraperitoneally with saline or Doxil for six weeks. These conditions recapitulate a dosing schedule used in human patients and are the same as those used in similar studies in mice. Mice are then tested with cognitive and behavior assays, and their brains are analyzed for aging and AD phenotypes.ResultIn our studies, we discovered that Doxil promotes cognitive impairment in wild‐type mice. We also found that the brains of young mice exposed to Doxil contain lipofuscin—a mixture of oxidized proteins and lipids that is usually found only in the aged or diseased brains. DNA damage occurred with Doxil treatment in mice, confirming Doxil accelerated features of brain aging. Critically, Doxil enhances the deposition of amyloid in Tg2576 mice.ConclusionOur study demonstrates evidence of accelerated brain aging in wild‐type mice and amyloid deposition in AD mice due to Doxil treatment. Our data provide a foundation for investigating chemotherapy as a potential risk factor for AD that warrants further study. This research is being pursued in our laboratory.
REM sleep is associated with the integrity of the cholinergic basal forebrain in aMCI participants
Authors: André Claire , Martineau‐Dussault Marie‐Ève , Daneault Véronique , Blais Hélène , Lorrain Dominique , Hudon Carol , Bastien Célyne , Petit Dominique , Lafrenière Alexandre , Legault Julie , Thompson Cynthia , Montplaisir Jacques , Gosselin Nadia , Carrier Julie 
Published: December 2022

AbstractBackgroundThe basal forebrain cholinergic system (BFCS) degenerates in Alzheimer’s disease (AD) before the onset of dementia. Interestingly, rapid‐eye movement (REM) sleep is highly dependent on cholinergic activity. In AD patients, REM sleep duration is reduced but the underlying brain mechanisms are still unclear. Our objective was to investigate the associations between REM‐sleep quantity and BFCS integrity in participants with amnestic mild cognitive impairment (aMCI) compared to healthy controls.MethodSixty‐two participants (31 cognitively healthy: 66.8 ± 7.2 years old, 13 women; 31 aMCI: 68.3 ± 8.8 years old, 7 women) underwent polysomnography and structural magnetic resonance imaging examinations. REM sleep duration (number of minutes) and proportion (%) were computed. All participants had a REM sleep apnea‐hypopnea index <15. T1‐weighted images were preprocessed using CAT12 and the DARTEL algorithm, and the mean intensity of BFCS subregions (i.e., Ch1‐2‐3, Ch4 and total BFCS) was extracted using the JuBrain Anatomy Toolbox. Multiple regressions were performed between BFCS subregional intensities and REM sleep indices controlling for age, sex and total intracranial volume, in the whole cohort and in the two groups separately.ResultIn the whole cohort, REM sleep duration and proportion were positively associated with Ch4 intensity (duration: r = 0.31, p = 0.017; proportion: r = 0.35, p = 0.007; Figure 1A and B) and total BFCS intensity (duration: r = 0.31, p = 0.016; proportion: r = 0.29, p = 0.024). Analyses stratified by cognitive status showed the same pattern in aMCI participants: REM sleep duration and proportion were positively associated with both Ch4 intensity (duration: r = 0.44, p = 0.018; proportion: r = 0.49, p = 0.009; Figure 1C and D) and total BFCS intensity (duration: r = 0.46, p = 0.014; proportion: r = 0.46, p = 0.013). No significant association, nor trend, was found in cognitively healthy participants (Figure 1C and D).ConclusionIn aMCI participants, lower REM sleep duration and proportion were associated with a decreased integrity of the BFCS, especially the Nucleus Basalis of Meynert. Our results support the notion that REM sleep alterations are an early marker of the degeneration of the BFCS in prodromal AD, before the onset of dementia.
Air pollution and dementia using longitudinal electronic health record data from the Indian Health Service
Authors: Zhu Yachen , Shi Yuxi , Manson Spero , O'Connell Joan , Jiang Luohua 
Published: December 2022

AbstractBackgroundAir pollution has been identified as an important risk factor for dementia in previous studies. As a unique population with a history of colonization, American Indians have long been disproportionately affected by air pollution. However, few studies have investigated the effects of air pollution on the risk of developing dementia in American Indians. This study aims to address this important knowledge gap.MethodCounty‐level average air pollution data in 2003‐2007 were downloaded from the land‐use regression models developed by the Center for Air, Climate, & Energy Solutions (CACES) and merged with data from the Indian Health Service (IHS) National Data Warehouse and related electronic health record databases between fiscal year (FY) 2007‐2013. We assigned air pollution exposure to IHS users based on their county of residence and calculated 5‐year averages of PM2.5, O3, CO, and NO2 in each county. A total of 14,910 American Indians who were 65+ years old in FY2007, used IHS services at least once each year, and were dementia free between FY2007‐2009 were included in the main analysis. Cox proportional hazard models with age as the time scale were employed to examine the association of air pollution with dementia incidence, adjusting for potential confounders.ResultThe PM2.5 levels in the IHS counties were lower than those in all US counties during 2003‐2013, while the levels of other air pollutants were similar to the US (Figure 1). More dementia incident cases were found in IHS counties with higher O3 levels (Figure 2). In multivariable Cox regression models (Table1), we found a significant positive association between dementia and O3 with a hazard ratio (HR) of 1.26 (95% CI: 1.02‐1.55) per 1 ppb standardized O3, while the associations between dementia and PM2.5, and CO were not statistically significant. We found similar results in sensitivity analyses using longer lags between air pollution and dementia or replacing CO by NO2 in the regression model.ConclusionOur study suggests that exposure to O3 is associated with the higher risk of dementia in American Indians. Future efforts to reduce exposure to air pollution might help lower dementia risk in American Indian communities.