bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update from the ReDLat consortium
Authors: Ibanez Agustin ,   ReDLat
Published: December 2023

AbstractBackgroundThe prevalence of dementia is notably high among Latinos, the largest and fastest‐growing minority community in the United States (US). Relatedly, brain health problems and dementia prevalence in Latin American countries (LACs) are overgrowing, along with the consequent clinical, social, and economic burden upon patients and their families. The Multi‐partner consortium to expand dementia research in Latin America (ReDLat) aims to identify AD and FTD’s genetic and socioeconomic/social determinants of health (SES/SDH) in LACs vs. the US.MethodI will provide an update regarding recruitment, multimodal data harmonization, and clinical, genetic, cognitive, and multimodal neuroimaging.ResultI will first present the sporadic and familial cases assessed, including patients with different genetic risk/mutations (PGN, TREM2, c9orf72, NAPT, TARDBP, PSN1/2, PRNP, ABCA7). I will present the first set of whole genome sequencing and the admixture analysis (57.8% Admixed American, 35.6% European, and 6.2% African). Then I will describe the progress regarding (1) contributions to AD and FTD, (2) SES/SDH impact on clinical‐cognitive‐neuroimaging signatures; (3) machine‐learning and computational approaches for brain‐phenotype characterization. Then the ReDLat expansion to (a) plasma biomarkers, (b) social epigenetics, and (c) natural speech analysis will be introduced. The renewal (2024) will expand ReDLat to include more familial presentations.ConclusionFocused on understanding non‐stereotypical, diverse, and underserved populations, we hope that ReDLat will promote the harmonization of global strategies to study, treat, and ultimately prevent dementia.
Amyloid/Tau/Neurodegeneration (ATN) image‐based biomarker trajectories of Alzheimer’s disease through 5‐year longitudinal follow‐up
Authors: Kim Han‐Kyeol , Cho Hanna , Lee Myung Jun , Lee Jae Hoon , Chun Joong‐Hyun , Ryu Young Hoon , Lyoo Chul Hyoung 
Published: December 2023

AbstractBackgroundTo investigate the progression of Alzheimer’s disease (AD) in image‐based Amyloid/Tau/Neurodegeneration (ATN) biomarkers through 5‐year longitudinal follow‐up.MethodAmong the participants who completed 18F‐florbetaben (FBB) for amyloid and 18F‐flortaucipir (FTP) for tau positron emission tomography (PET), and brain magnetic resonance (MR) imaging for neurodegeneration at a first visit, we enrolled the 145 participants who the studies at least twice [67 amyloid negative cognitive unimpaired (A‐CU), 10 amyloid positive cognitive unimpaired (A+CU), 68 amyloid positive cognitive impaired (A+CI)]. 70 participants completed the scans twice (25.2±3.1, months), and 75 participants completed the scans three times (57.9±7.4, months). We estimated the temporal trajectories of ATN biomarkers using a restricted cubic spline model and modified Euler method between baseline and annual change rates. The standardized uptake value ratio of FBB/FTP PET and hippocampal volume were used for representing each ATN biomarker, respectively.ResultThe FBB curve of the global cortex and AD‐specific regions reaches a plateau with a sigmoid appearance. FTP curves in the regions for Braak stages I‐II and III‐IV show similar sigmoid appearance while the global cortical and stage V‐VI tau curves show an exponential increase continuously. The hippocampal volume curve shows a linear decrease until the time point when the tau accumulation begins in the Braak stage I‐II, then decreases to a reversed sigmoid appearance.ConclusionLike the already known saturation of amyloid burden, it was also shown that the tau burden of the region for Braak stages I‐II and III‐IV saturated, but not in Braak stages V‐VI. Hippocampal atrophy seems to accelerate when tau begins to accumulate in early Braak stage regions. In future work, it is necessary to enroll patients at an advanced stage and collaborate with an international cohort.
Receptor specific mechanisms underlying psychedelic effects on affective behaviors
Authors: Jaques Yanabah , Ko MeeJung , Kaufer Daniela 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) patients experience affective symptoms. Conventional therapies to address affective symptoms have limited efficacy in AD, alternative options, like psychedelics, have received interest. Psychedelics work through serotonergic pathways ‐ a neuromodulatory system with dysfunction in AD ‐mechanisms underlying behavioral changes and potential efficacy of their use are unknown. Evaluation of mechanisms underlying behavioral effects is needed to determine their potential as interventions. Psychedelics act through serotonin receptors, not serotonin re‐uptake inhibition characteristic of typical antidepressants. We investigate psychedelics’ mechanism of action as a potential effector of hedonic tone to assess its potential use for affective symptoms in AD.MethodWT mice were subject to one of three paradigms: (1) a 10‐day social defeat stress (SDS); (2) an injection of 2,5‐Dimethoxy‐4‐iodoamphetamine (DOI); or (3) SDS with DOI. SDS was used instead of an AD proteinopathy model to induce effects like anhedonia. Afterwards, mice underwent behavioral tests to evaluate compulsivity and affect. An additional group will receive DOI +serotonin receptor antagonistsResultFirst, SDS increased time spent in closed arms of the elevated plus maze (EPM; p = 0.0068) indicating an increase in anxiety. It also increased nest shredding (NST; p = 0.206), indicating an increase in compulsivity.Secondly, an injection of DOI decreased time spent in closed arms (p = 0.0151) indicating decrease in anxiety, and decreased nest shredding (p = 0.0325) indicating a decrease in compulsivity.Lastly, we expect that DOI will decrease anxiety and compulsivity. We expect to find the inverse to be true in mice that receive DOI +antagonist.ConclusionWe are showing that a traumatic stressor, like that a human might experience pre‐AD, induces potentially maladaptive affective behavioral changes. Here, we’ve demonstrated that psychedelics can act to recover affective dysfunction by activation of serotonin receptors. Because of degeneration of key serotonergic nuclei in AD, the use of serotonin reuptake inhibitors has limited efficacy for addressing symptoms like depression. Psychedelics may offer improved outcomes for AD patients in this regard due to its alternative mechanism of action. Further work to evaluate the efficacy of psychedelics in animal models more closely approximating AD‐type changes in serotonergic systems will help refine this understanding and guide potential clinical applications.
TREM2 protects against complement‐mediated synaptic loss via binding to C1q in neurodegeneration
Authors: Chen Xiao‐Fen 
Published: December 2023

AbstractBackgroundThe triggering receptor expressed on myeloid cells 2 (TREM2) is recognized as the strongest immune‐specific genetic risk factor for Alzheimer’s disease (AD), since its heterozygous R47H variant confers a 3‐4‐fold increased risk of AD. It has been widely acknowledged that TREM2 plays versatile roles in regulating microglial functions by interacting with a variety of ligands.MethodWe performed affinity‐purification coupled to mass spectrometry with the TREM2‐Fc fusion construct to identify new binding partners for TREM2. The binding of TREM2 to new partners was further confirmed by a solid‐phase binding assay, surface plasmon resonance assay, dot blot binding assay and proximity ligation assay. Next, the functional effects of TREM2 binding to new partners were determined both in vitro and in vivo. We further performed serial truncations to determine the amino acid sequence in TREM2 responsible for binding to new partners. Finally, the functional effects of TREM2 peptide binding to new partners were examined in both the physiological and pathological contexts.ResultHere we show that C1q protein, the initiator of the classical complement pathway, is a binding partner for TREM2. TREM2 specifically attenuated the activation of classical complement cascade via high‐affinity binding to C1q in vitro. The formation of TREM2‐C1q complexes was also detected in human AD brain. Remarkably, the increased density of TREM2‐C1q complexes was associated with lower deposition of C3 but higher density of PSD95, pinpointing to a protective role of TREM2 against complement activity in AD brain. In mice expressing mutant human tau, Trem2 haploinsufficiency increased complement‐mediated microglial engulfment of synapses and accelerated synaptic loss with negligible effects on microglial density and tau pathology. We further identified a 41 amino acid sequence in TREM2 responsible for binding to C1q. In vivo administration of this short peptide reduced synapse removal by microglia and rescued synapse density in both the amyloidosis and tauopathy mouse models of AD.ConclusionTogether, our results demonstrate a critical role for microglial TREM2 in restricting complement‐mediated synaptic elimination in neurodegeneration, providing new mechanistic insights into the protective roles of TREM2 against AD pathogenesis.
The association of English‐Spanish and Indigenous‐Spanish bilingualism with cognition among older adults in the Mexican Health and Aging Study (MHAS)
Authors: Renteria Miguel Arce , Petrosyan Sarah , Saenz Joseph , Arango Silvia Mejia , Aguila Emma , Barral Sandra , Tosto Giuseppe , Reyes‐Dumeyer Dolly , Samper‐Ternent Rafael , Obregon Alejandra Michaels , Wong Rebeca 
Published: December 2023

AbstractBackgroundWhile several studies have reported a “bilingual advantage” in cognition among older adults, others have not. Most studies of bilingualism and cognitive aging are in urban settings among high income countries, limiting the generalizability among bilinguals residing in lower‐and middle‐income countries, such as Mexico. Additionally, the association of bilingualism and cognition among indigenous populations is unknown. In Mexico, there are almost 7 million speakers of indigenous languages, residing primarily in rural areas, and over 15 million people that report speaking English, predominantly in urban settings. To account for sociocultural factors confounding the type of bilingualism (i.e., English‐Spanish, Indigenous‐Spanish), we evaluated whether bilingualism was associated with better cognitive functioning among adults across urban and rural regions in Mexico.MethodAnalyses included participants from the Mexican Health and Aging Study (MHAS) aged 55 and older in urban (N = 1053, 12% Spanish‐English bilinguals) and rural (N = 814, 20% Spanish‐Indigenous bilinguals) areas. Participants reported speaking English and/or an indigenous language in addition to Spanish. Participants completed comprehensive cognitive testing assessing memory, language, executive function, and visuospatial domains. General linear models stratified by region evaluated bilingualism on cognitive domain performance covarying for sociodemographic factors.ResultSociodemographic characteristics differed by region and language group. English‐Spanish bilinguals in urban areas were younger, predominantly men, with higher education, less likely illiterate, and with greater U.S. migration history compared to monolinguals. In rural areas, Indigenous‐Spanish bilinguals were younger, with less education, higher prevalence of illiteracy, and less likely to have U.S. migration history compared to monolinguals. In urban settings, English‐Spanish bilingualism was not associated with performance on any cognitive domain (p>0.05). In rural settings, Indigenous‐Spanish bilingualism was associated with worse performance across all cognitive domains (p<0.01).ConclusionThere was no evidence of a bilingual cognitive advantage among older adults residing in urban and rural regions in Mexico. While indigenous bilinguals demonstrated the lowest cognitive test performance, further work is required to understand the socioeconomic and environmental factors associated with bilingualism among indigenous populations in Mexico. Greater characterization of their bilingualism (i.e., age and context of acquisition, proficiency, frequency of use) across all languages can help elucidate the association between bilingualism and cognitive test performance.
Nuestro día (our day): The daily experiences of Latino ADRD family caregivers
Authors: Puga Frank , Wang Danny , Poe Abigail A. , Alvarez Loreli 
Published: December 2023

AbstractBackgroundThe prevalence of Alzheimer’s disease and related dementias (ADRDs) among the Latino population is 1.5 times higher than non‐Hispanic whites. Latinos develop ADRDs earlier and experience more severe symptoms than other ethnic and racial groups. Further, comorbidities, including diabetes, heart disease, and hypertension, have also been observed among Latino individuals living with ADRDs — introducing additional health issues, exacerbating ADRD‐related symptoms, and accelerating functional decline. Given these observed disparities, Latino ADRD family caregivers are uniquely susceptible to increased caregiving stress that can negatively impact their mental health over time. Previous studies have reported on stress and well‐being among Latino ADRD caregivers; however, relatively little is known about the day‐to‐day caregiving experiences and mental health of Latino caregivers. Thus, the purpose of this study was to examine daily contextual factors and variations in depression symptom experience among Latino ADRD family caregivers.MethodsA national sample of Latino family caregivers (N = 71) completed daily diary surveys over 21 days (n = 2,481). Mixed‐level modes were used to examine relationships between daily caregiving stress, stress moderators, and depression‐related symptoms.ResultsLatino ADRD caregivers were more likely to report depression (OR = 1.14, 95% CI: 1.03‐1.25, p < 0.01) on a given day when behavioral symptoms of dementia were present and perceived as more bothersome than usual. A decrease in the daily odds of depression was observed on days when Latino ADRD caregivers reported receiving social support (OR = 0.69, 95% CI: 0.58‐0.82, p < 0.01), engaging in social activities with friends or other family members (OR = 0.38, 95% CI: 0.25‐0.58, p < 0.01), and engaging in self‐care activities (OR = 0.65, 95% CI: 0.46‐0.92, p < 0.05).ConclusionThis study offers insight into the daily experiences and mental health of Latino ADRD family caregivers by identifying specific stressors and stress moderators associated with depressive symptoms experienced on a given day. The results of this study highlight modifiable factors for ecologically valid and culturally relevant interventions that mitigate the adverse effects of caregiving stress. Such interventions are critically needed as Latino caregivers are an underserved and underrepresented population in dementia care and aging research.
Glomerular filtration rate proteinuria and risk of dementia: a cohort study from the national health insurance database
Authors: Oh Mi‐Young , Kim Hyun Jung Kim , Lim Jae Sung , Ahn Hyeong Sik 
Published: December 2023

AbstractBackgroundThe previous studies had shown conflicting results about the association between kidney dysfunction and dementia. One of the causes may be the use of different indicators to define kidney dysfunction. Although estimated glomerular filtration rate (eGFR) and proteinuria reflect the kidney’s different aspects, few studies used both indicators to examine the association between kidney dysfunction and dementia. In addition, even in the same study, the correlation between kidney dysfunction and dementia was different depending on the indicator. We aimed to demonstrate the association between kidney dysfunction and dementia using renal indicators‐ eGFR and proteinuria independently or together.MethodWe used the National Health Insurance database covering the entire population in South Korea to identify and follow up with the population who checked up in the National Health Screening Program (NHSP) from January 2009 to December 2010. Dementia was defined as a newly diagnosed dementia among the population without a history of dementia before enrollment. We used Cox proportional hazard model to examine between eGFR or proteinuria and the risk of dementia.ResultThere were 283,747 incident dementia cases during 132,811,487 person‐years of follow‐up. The risk of dementia was progressively higher with lower eGFR; compared to eGFR≥100 mL/min, hazard ratio (HR) 1.09, confidence interval [CI], 1.07‐1.12 in eGFR 90‐100 mL/min, HR 1.08, 95% CI, 1.06‐1.10 in eGFR 60‐90 mL/min, HR 1.22, 95% CI, 1.19‐1.24, in eGFR 30‐60 mL/min, HR 1.99, 95% CI, 1.86‐2.12 in eGFR 15‐30 mL/min, and HR 3.05, 95% CI, 2.96‐3.14 in eGFR <15 mL/min or dialysis. The proteinuria was also correlated with dementia (HR 1.25, 95% CI, 1.23‐1.27) after adjusting eGFR. Proteinuria contributed to the stratification of the high‐risk patients for dementia in each eGFR stratum; HR 1.39[95% CI, 1.26‐1.53]in eGFR ≥100 mL/min, HR 1.28[95% CI, 1.21‐1.35]in eGFR 90‐100 mL/min, HR 1.23[95% CI, 1.20‐1.27] in eGFR 60‐90 mL/min, HR 1.24[95% CI, 1.20‐1.28] in eGFR 30‐60 mL/min, HR 1.06[95% CI, 0.89‐1.26] in eGFR 15‐30 mL/min, and HR 1.16[95% CI, 1.10‐1.22] in eGFR <15 mL/min or dialysis.ConclusioneGFR and proteinuria were associated with dementia independently. The use of both eGFR and proteinuria was useful for the stratification of dementia risk.
Direct Head Injection of Streptozotocin elicits Behavioral Deficiencies and Neurochemical Alterations Characteristic of Neurodegeneration in Lobster Cockroach; Nauphoeta cinerea (Blattodea: Blaberidae) Model
Authors: Famutimi Mayokun Ebunolu 
Published: December 2023

AbstractBackgroundNeurodegeneration diseases are a group of diseases like Alzheimer’s disease that are characterized by poor cognitive abilities, neuromuscular deficiencies and locomotion difficulties. The goal of biomedical research is to seek to explore suitable experimental models to study such neurological disorders. Such suitable models must underscore the 3Rs of alternative research models ‐ replacement, reduction and refinement. The lobster cockroach (Nauphoeta cinerea) is one such model that is gaining global attention for their suitability to study human‐related diseases. Therefore, this study aims to model neuromuscular deficiencies and neurodegeneration associated with impaired glucose homeostasis in lobster cockroach (Nauphoeta cinerea).MethodAcute neurotoxicity was achieved by injecting 74 and 740 nm streptozotocin (STZ) injection per cockroach head and the cockroaches were monitored for 7 days. Thereafter, their survival rate, mortality and behavioral profiles for neuromuscular function including the total time immobile, total distance traveled, time spent in periphery and average speed were assessed on the seventh day, after which the cockroaches were assayed for biomarkers of neurodegeneration and oxidative stress.ResultThe results showed that the survival rate, average speed and total distance traveled were reduced significantly, while STZ increased the mortality, time spent in periphery and total time immobile. Furthermore, STZ induced an increase in acetylcholinesterase activity, lipid peroxidation and total reactive oxygen species. In addition, the results also suggest an impairment in glucose‐trehalose conversation mechanism.ConclusionThese results are obvious indications of behavioral impairments and metabolic disruptions which affect neuromuscular function and are indices of neurodegeneration. This therefore, suggests that direct injection of STZ to cockroach head is a useful, effective and reproducible model in evaluating neuromuscular deficiencies and neurodegeneration associated with brain glucose metabolic dysregulation.
Incidence and symptomatology of ARIA
Authors: Filippi Massimo 
Published: December 2023

AbstractBackgroundTo summarize available evidence on ARIAs from randomized clinical trials (RCTs) testing anti–β‐amyloid mAbs in patients with AD and to provide a comprehensive update about risk factors, clinical correlates, and implications for withholding and reinitiating treatment.MethodA literature search of MEDLINE/PubMed, Embase, and Cochrane Library and a search of ClinicalTrials.gov were conducted through September 15, 2021. Publications describing RCTs, secondary analyses of RCT data, and case reports of ARIAs were included. Strengths of clinical data were graded according to the Oxford Centre for Evidence‐Based Medicine.ResultTwenty‐two RCTs, 11 secondary analyses of RCTs, and 1 case report, including in total 15 508 adult patients (8483 women [54.7%]; mean [SD] age, 69.6 [8.3] years) were selected for inclusion. Signal alterations that included parenchymal edema and sulcal effusion leading to transient hyperintensities on fluid‐attenuated inversion recovery and T2‐weighted sequences were termed ARIA‐E, whereas those consisting of hemosiderin deposits, including parenchymal microhemorrhages and leptomeningeal superficial siderosis, were termed ARIA‐H. Apolipoprotein E (ApoE) ε4 genotype was the main risk factor for both ARIA types; ARIA‐E incidence was further associated with treatment dose, affecting the 55%of ApoE ε4 carriers in the high‐dose aducanumab treatment group. Both ARIA types manifested early during study course, and symptomatic cases accounted for the 6.1% to 39.3%of ARIA‐E cases at higher treatment doses across RCTs, whereas ARIA‐H cases were generally asymptomatic. Most ARIA‐E cases resolved with treatment withholding, although corticosteroid administration was required anecdotally. ARIA‐E recurrence after dose reinitiation or adjustment varied from 13.8% to 25.6%across RCTs.ConclusionEvidence suggests that ARIAs are frequent, mostly asymptomatic collateral events of amyloid‐modifying therapies, highlighting the need for standardized clinical and neuroradiological management protocols in real‐world clinical settings.