bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comprehensive, Community‐Engaged Recruitment Strategy to Increase Minority Representation in New IDEAS – an Amyloid Imaging Study
Authors: Wilkins Consuelo H. , Dilworth‐Anderson Peggye 
Published: December 2023

AbstractBackgroundAlthough Black and Hispanic/Latino people have higher rates of clinical Alzheimer disease (AD), evidence indicates lower proportions and odds of positive amyloid positron emission tomography (PET). This may indicate differences in etiology of cognitive impairment, which has implications for prevention and treatment (ie, anti‐amyloid treatments). Unfortunately, Black and Hispanic/Latino people are underrepresented in AD research.MethodTo evaluate amyloid PET in a diverse sample, we designed culturally‐informed, community‐engaged recruitment strategies for New IDEAS (Imaging Dementia—Evidence for Amyloid Scanning), an observational, open‐label, longitudinal cohort study of beta‐amyloid PET. New IDEAS intends to recruit 7,000 U.S. Medicare beneficiaries with mild cognitive impairment (MCI) or dementia including 2,000 Black/African American and 2,000 Latino/Hispanic individuals. To ensure diversity, we developed a comprehensive recruitment strategy using a diverse, culturally‐trained staff that includes:• Identifying Dementia Specialists experienced recruiting minorities• Embedding high‐impact community engagement in select regions• Increasing capacity of specialists and PET facilities to engage minorities• Increasing pipeline of referrals to Dementia Specialists• Creating a culturally‐informed awareness campaignResultNew IDEAS has enrolled 4,524 participants including 954 (21.1%) Black/African American, and 842 (18.6%) Hispanic/Latinx. Median age is 76 years; 54% are female. More Black/African American (46.6%) and Hispanic/Latinx (42.6%) participants had a dementia diagnosis compared to the overall cohort (33.9%). More Black/African American (37.4%) and Hispanic/Latinx (37%) participants were enrolled in Medicare Advantage compared to the overall cohort (19.5%).During implementation, we encountered additional barriers to minority participation including: dementia specialists and PET facilities located greater distance from minority neighborhoods, lack of transportation to visits, fewer academic medical sites registered, concerns about co‐pays, and dementia specialists not accepting new patients. New strategies are being implemented to address some of barriers including coverage of co‐pays and assistance with transportation.ConclusionNew IDEAS has enrolled more Black/African American and Hispanic/Latinx participants than any amyloid PET study published to date. Despite some success with minority enrollment, recruitment has been hampered by underlying structural barriers such as lack of access to dementia care in minority communities and higher Medicare Advantage rates. Additional resources and policy changes are needed to allow more equitable access to research and dementia care.
Tau maturation in clinicopathological spectrum of Lewy body and Alzheimer’s disease
Authors: Arezoumandan Sanaz , Cousins Katheryn A Q , Ohm Daniel T , Lowe MaKayla , Phillips Jeffrey S , McMillan Corey T , Siderowf Andrew , Chen‐Plotkin Alice , Deik Andres , Spindler Meredith , Tropea Thomas F. , Weintraub Daniel , Wolk David A. , Grossman Murray , Lee Eddie B , Irwin David J. 
Published: December 2023

AbstractBackgroundIn Alzheimer’s disease neuropathologic change (ADNC), maturation of neurofibrillary tangles and tau pathology are characterized by posttranslational modifications of tau. ANDC and Lewy body disease (LBD) commonly co‐exist in aging brains and there are overlapping clinical syndromes and heterogeneity in clinical features among cases with mixed ADNC and LBD pathology. Given this clinical and pathological overlap, we examined the postmortem expression of tau conformational epitopes that mark various stages of tangle maturation in clinicopathologic spectrum of Alzheimer’s disease (AD) and LBD.MethodAutopsy‐confirmed cases with diffuse neocortical LBD with/without ADNC (n = 59) were selected (Table1). We used digital histology methods to measure percent area occupied (%AO) with pathology in three regions (middle frontal, anterior cingulate, and superior temporal cortices) immunohistochemically stained with MJF‐R13 (α‐synuclein), NAB228 (beta‐amyloid), and tau monoclonal antibodies marking phosphorylated (AT8), early conformational (MC1, preferentially reactive in pre‐tangles), and C‐terminally truncated tau epitopes (TauC3, preferentially reactive in mature intracellular and ghost tangles). Linear models tested the group comparisons, and correlation between α‐synuclein or beta‐amyloid with outcome of average neocortical tau. In models, %AO were log‐transformed, and age and sex were included as covariates.Resultα‐synuclein was strongly correlated with early tau epitopes labelled with AT8 (β = 1.37, p<0.001) and MC1 (β = 1.20, p<0.001), but not with mature tau epitopes detected by TauC3 (p = 0.38). There were significant positive correlations between all tau epitopes and beta‐amyloid, including TauC3 immunoreactive tau (p≤0.013) (Figure1). In the mixed pathology group, those with clinical LBD had a positive association between α‐synuclein and MC1 (β = 1.61, p = 0.014) and AT8 (β = 1.67, p = 0.005) positive tau, while those with clinical AD had no correlation between α‐synuclein and tau epitopes. There was greater MC1 (β = 3.40, p<0.001), AT8 (β = 3.59, p<0.001), and TauC3 (β = 1.43, p = 0.005) pathology in patients with clinical AD compared to clinical LBD.ConclusionIn LBD, higher α‐synuclein is associated with greater phosphorylated and early tau conformations, but not later conformation of mature tau, which was selectively associated with beta‐amyloid pathology. Our findings suggest that tau pathology may modify the clinical expression of synucleinopathies and C‐terminal truncation of tau may be more closely related to AD pathophysiology than synucleinopathy.
Whole‐exome sequencing of a Portuguese cohort of early‐onset Alzheimer’s disease implicates X‐linked lysosomal gene GLA
Authors: Tábuas‐Pereira Miguel , Guerreiro Rita , Bras Jose , Santana Isabel , Tredici Kelly , Paquette Kimberly , Taipa Ricardo 
Published: December 2023

AbstractBackgroundCerebrovascular disease is a common comorbidity in patients with Alzheimer’s disease (AD) and other dementias. Accumulating evidence indicates that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. In fact, some studies have associated common variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 with AD pathogenesis.We aimed to identify rare genetic variants in genes associated with monogenic small vessel disease in in a cohort of Portuguese early‐onset AD patients.MethodWe performed whole‐exome sequencing in a cohort of 104 thoroughly studied patients with early‐onset AD, without known pathogenic variants in the genes associated with AD or frontotemporal dementia. In these patients, we searched for rare (MAF<0.001) non‐synonymous variants in genes associated with small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2, CSTA, GLA and TREX1.ResultIn total, we found 12 rare variants in 18 patients. We found 3 male AD patients with a pathogenic GLA variant. We found other rare variants in NOTCH3, COL4A2 and HTRA1. Of the 3 patients carrying a GLA variant, one had a neuropathological study confirming the diagnosis of AD . This individual also revealed Fabry disease pathology in the hippocampal formation (CA1 to CA4 and subiculum).ConclusionWe found several rare variants on the genes of interest in our cohort. We provide evidence supporting the pathogenicity of the GLA variant. We show that 3 carriers of this variant, without other probable genetic cause responsible for the disease, developed early‐onset AD. One of those cases had post‐mortem confirmation of the diagnosis. We further show the localization of Fabry pathology in several areas that are vulnerable in AD. This poses the question of the variant’s possible role in AD pathogenesis.
Higher circulating cortisol is associated with amyloidogenesis in post‐menopausal women: The Framingham Heart Study
Authors: Salardini Arash , Zilli Eduardo Marques , Himali Jayandra Jung , Gonzales Mitzi M. , Himali Dibya , Ghosh Saptaparni , McGrath Emer R , Buckley Rachel F. , Satizabal Claudia L. , Johnson Keith A. , Decarli Charles , Fakhri Georges El , Vasan Ramachandran S , Seshadri Sudha 
Published: December 2023

AbstractBackgroundReports of a correlation between higher baseline cortisol and faster progression of Alzheimer’s disease (AD) in longitudinal cohorts and more advanced AD pathology in cross sectional studies raise the possibility that cortisol dysregulation contributes to AD pathogenesis. The current data, however, is less strong with regards to possible mechanisms underlying this relationship or the direction of influence between higher cortisol and AD severity. The goal of this study was to examine the associations between cortisol levels and incident cerebral amyloid and tau PET deposition.MethodsWe present a prospective cohort study of cognitively normal individuals derived from Framingham Heart Study (generation 3‐mean age 39.6±8.1 years, 48.5% women) who had measures of fasting morning plasma cortisol at baseline and PET measures of brain amyloid and tau 15±1.6 years later. Fasting cortisol levels were examined as tertitles (Cortisol level (min,max)‐ T1:3.92‐11.12; T2:11.13‐15.50; T3:15.76‐50.07). Linear regression was used to evaluate associations baseline plasma cortisol (in tertiles) with amyloid and tau deposition, adjusted for age, sex, and the duration between cortisol and PET imaging assessments. We assessed interactions by ApoE4 positivity, sex and menopausal status (women only).ResultsWe found no association between serum cortisol and amyloid/tau burden, and no significant interaction with age or ApoE4 status. However, the association between cortisol and amyloid retention interacted significantly with sex in our primary regions of interest (posterior cingulate cortex [PCC] β:0.059±0.027, p = 0.031; precuneus [PC] 0.071±0.025, 0.005, and whole brain [represented by FLR] 0.039±0.014, 0.006). Comparing the highest relative to the middle cortisol (the referent) tertiles among women, amyloid deposition was higher in PCC (β±SE: 0.059±0.027, p = 0.031), PC (0.071±0.025, 0.005), and FLR ROIs (0.039±0.014, p = 0.006). The same relationships did not hold in men or in relations to tau. Furthermore, the effect was only present in postmenopausal women, with the higher amyloid deposition in PC (β:0.103±0.040, p = 0.012) and FLR ROIs (0.071±0.020, 0.001) as well as superior temporal sulcus (secondary outcome). We did not observe any statistically significant association comparing bottom to the middle cortisol tertile.ConclusionAlthough future research is needed, the results suggest that serum cortisol may contribute to Alzheimer’s pathogenesis by driving amyloidogenesis in postmenopausal women.
Sentinels of the Social geriatric program: implementation in rural areas of network for the identification of seniors at rick secondary to loss of autonomy or cognitve deficits
Authors: Lacombe Guy , Lemire Stéphane , Bouffard Marie‐Pier 
Published: December 2023

AbstractBackgroundIn a large rural area, isolated seniors rarely consult health services and often come to emergency rooms after severe deterioration. The implantation of “sentinels” in their environment could make it possible to identify them early.MethodThe AGE Foundation, a charitable organization, in collaboration with the public health services of the Granit region (22,000 p/2731 Km2) in the province of Quebec developed care trajectories, identified caregaps and environments requiring sentinels. The project include the analysis of the implantation and the identified casesResultIn 2022, the nurse “navigator” trains 80 sentinels in the use of tracking tools such as AD‐Plus. The sentinels are home care workers and non‐professionals (hairdresser, grocer, municipal agents, etc.) well established in 16 communities. In 9 months they have raised more and more alerts, from 2 to 25 per month for a total of 129. The alerts concerned seniors with an average age of 79, 56 were between 80 and 89 years old and 18 over 90 years old. The majority, 66%, are women. But more importantly, 73% had no follow‐up in the health system before. They required an average of 20 days of targeted interventions, the vast majority of which took place at home.ConclusionMany seniors suffer from loneliness. At the beginning of loss of independence or cognitive impairment, do not consult health services. The “Sentinels” and the Navigator present an effective tracking model.
Chronic traumatic encephalopathy pathology in a large population‐based study.
Authors: Rodriguez Roberta Diehl , Nowinski Christopher , Suemoto Claudia Kimie , Leite Renata Elaine Paraizo , Ferretti‐Rebustini Renata Eloah de Lucena , Jacob‐Filho Wilson , Pasquallucci Carlos Augusto , Nitrini Ricardo , Grinberg Lea T. 
Published: December 2023

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease predominantly found in former athletes and associated with repetitive brain injury (TBI). Despite the increased number of studies, several questions about prevalence and risk factors for CTE in the general population remain unknown.Methodto investigate the presence of CTE pathology in a population‐based clinicopathological cohort, we analyzed brain sections immunostained with tau antibody (AT8) of 1151 individuals over 30 years of age with previous neuropathological assessment. The presence of CTE pathology was evaluated according to the current neuropathological consensus criteria. Demographic and clinical data were collected through interviews with a next‐of‐kin. All cases are from the Biobank for Aging Studies of the University of São Paulo University. Internationally accepted criteria were used to diagnose and stage the brain tissue pathologies.ResultOnly 7 cases (0.6%) met neuropathological criteria for CTE, contrasting with the high frequency of aging‐related tau astrocyte pathology (ARTAG) (50%) The mean age of death was 73.4 12.5 and only one individual were female. Presence of co‐pathologies was observed in all cases, being the most frequent comorbidity AD‐type pathology, followed by argyrophilic grain disease. Dementia was present in 43%, meanwhile 57% had some degree of neuropsychiatric symptoms (NPS). The most frequent NPS was depression, followed by anxiety. The history of sport practice was complete only for two cases. Both played soccer, however only one semi‐professionally.ConclusionThe low frequency of CTE pathology corroborate findings from other studies that CTE is not a frequent finding in population‐based samples. The overlapping between CTE and ARTAG may contribute with the misclassification of ARTAG as CTE.
Alzheimer´s Disease initial cognitive profile in an Argentinian cohort of individuals with Down Syndrome
Authors: Pertierra Lucia , Clas Giulia Solange , Tapajoz Fernanda , Helou Belén , Guimet Nahuel Magrath , Bérgamo Yanina , Vazquez Silvia , Sevlever Gustavo , Allegri Ricardo Francisco , Surace Ezequiel 
Published: December 2023

AbstractBackgroundDown Syndrome [DS] is the most frequent cause of genetic developmental and intellectual disability. The lifetime risk of Alzheimer’s Disease [AD] in people with DS is more than 90%, with an earlier age of onset than the general population. There is ongoing debate whether there are significant differences in dementia presentation in the specific context of DS, with some studies suggesting a predominantly frontal phenotype with behavioural symptoms and others suggesting a more frequent amnestic presentation.The aim of this study was to characterize the initial cognitive profile of AD in a cohort of Argentinian adults with DS.MethodAdults with DS and prodromal or established AD dementia who were part of the IASDA (Argentinian initiative for the study of DS and AD) cohort or spontaneusly attended our Memory Clinic were included. Initial cognitive profile was determined by a semi‐structured interview conducted by a cognitive neurologist with the subject, their family and caregivers.ResultSixteen adults with DS were included. Fifty‐six percent (n = 9) were males. Mean age was 51 yo (42‐59 yo). Sixty‐two percent (n = 10) had premorbid moderate intellectual disability [DI], 25% (n = 4) had severe DI and 13% (n = 2) had mild DI.Fifty‐six percent (n = 9) had a clinical diagnosis of prodromal AD, and the remaining individuals had clinically established AD dementia. Fifty percent (n = 8) had positive amiloid biomarkers (determined by cerebral PiB‐PET or cerebrospinal fluid levels of Aβ42, phosphorylated‐tau and total‐tau), while the remaining subjects did not undergo amiloid biomarker assessment. Due to cognitive impairment, premorbid language impairment and/or premorbid severe DI, only 25% (n = 4) of individuals completed neuropsychological testing (CAMDEX‐DS, Cued Recall Task).Initial cognitive profile was charactirized as amnestic (single‐domain amnestic or multiple‐domain amnestic) in 81% percent (n = 13) of the cohort. Only 13% (n = 2) of the subjects had initial non‐amnestic syndromes, and in one case (6%) the initial cognitive syndrome was uncertain.ConclusionAmnestic cognitive impariment was the most frequent presentation of AD in this small cohort of Latin American adults with DS.
Sharing History through Active Reminiscence and Photo‐imagery‐SHARP: Feasibility and acceptability of digital biomarker technology among older Black adults
Authors: Croff Raina , Beattie Zachary T , Gothard Sarah , Fuller Patrice , Fennell Charles T , Kaye Jeffrey A 
Published: December 2023

AbstractBackgroundMore nuanced data collection beyond pre/post measures can detect real‐time changes in activity levels, sleep, and other factors that may signal transition in cognitive health.MethodNine Black adults (n = 4 healthy, mean age 71.1; n = 5 mildly cognitively impaired (MCI), mean age 79.2) tested the feasibility of adding digital biomarker technology to the SHARP walking study in Portland, Oregon. Up to 8 weeks, participants wore an actigraphy watch that captured continuous activity data, used an under‐the‐mattress sensor that captured daily sleep data, and completed online health forms that captured weekly changes. The second 4‐8 weeks and in triads, participants walked and conversationally reminisced together on three 1‐mile routes/week using the SHARP smartphone application. Means were calculated from group aggregated data (MCI/healthy). Content analysis of group discussions assessed technology acceptability.ResultWatch step data was collected on average 60.4±51.2 days per participant, representing on average 75.0±29.2% of the days step data was collected. Watch sleep data was collected on average 47.6±40.5 days per participant, representing on average 62.5±33.7% of the days sleep data was collected. Under‐the‐mattress sensor sleep data was collected on average 79.3±42.9 days per participant, representing on average 79.0±24.8% of the days sensor data was collected. MCI participants had lower mean daily step count at 1140 compared to 2570 steps for healthy participants, and lower mean sleep time at 5.07 hours compared to 6.71 hours for healthy participants. MCI had lower mean survey response rates, even with weekly reminders, at 60% compared to 91% for healthy participants, and notably longer mean response times at 472 seconds compared to 195 seconds for healthy participants. Participants generally accepted technology, with caveats: more explanation of technology, better watch step count displays, and watch band options as silicone was uncomfortable in heat and water, prompting discontinuous wear.ConclusionUsing digital biomarker technology for more continuous data capture with older adults including those with MCI is feasible. However, teams should anticipate increased support for MCI participants and potentially longer technology deployment and set‐up. More continuous data reveal real‐time changes that may signal transitions in cognitive health, allowing for a timelier response from healthcare partners.
HSV‐1 reactivation in AD mouse model reveals longitudinal reduction in synaptic gene expression in the brain
Authors: Funk Cory C , Robinson Max , Schaffer Caitlyn , Battaglia Christian , Aubert Martine , Wiley Jesse C , Cary Gregory A. , Johnston Christine , Darvas Martin 
Published: December 2023

AbstractBackgroundMounting evidence supports the contribution of neurotrophic herpesvirus family infections to Alzheimer’s Disease (AD) etiology on the molecular, physiologic, and epidemiologic levels. As chronic viral infections have substantial variability in reactivations, and AD pathology is known to begin over a decade prior to symptoms, understanding the longitudinal impact of herpesviruses on AD pathogenesis is a challenging and complex problem.MethodWe developed a mouse model of herpes‐simplex virus type 1 (HSV‐1) infection in C57B6/J mice containing humanized APP and APOE4. Using 10 mice per group (5 male, 5 female), and after initial infection at 2 months of age via corneal scarification with 106 PFU HSV‐1 strain 17, we reactivated the virus with the bromo‐domain compound JQ1 at 4, 6 and 10 months, with 1x, 3x and 6x reactivations respectively. We included both mock transfected and JQ1‐only treated mice as controls.ResultWe found reactivation by JQ1 resulted in increased HSV‐1 detection by qPCR in a progressive manner, emanating outward from the trigeminal ganglion, towards more distal brain regions. One month post reactivation, we harvested multiple brain regions (brainstem, hippocampus, entorhinal cortex, and dural sinus) for RNAseq expression profiling one month after the last reactivation (i.e. latent HSV‐1 infection) to allow for the immune system to clear the active reactivation and observe long‐term changes in gene expression. We found many synaptic genes down regulated in the entorhinal cortex at 10 months, with 6 reactivations, compared to mock infected. We additionally saw decreases in gene expression in lipid metabolism, myelination, and the endolysosomal pathways. In the brain stem, where HSV‐1 viral levels were found at higher levels, gene expression patterns showed increase immune‐cell related activity.ConclusionOur HSV‐1 reactivation mouse model enables characterization of the impacts of HSV‐1 infections on neuronal gene expression. These changes are consistent with observed changes in gene expression in humans, and help contextualize the putative mechanisms by which HSV‐1 contribute to Alzheimer’s disease etiology.