bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levels of plasma ADAM10, education, and cognitive performance of healthy older adults and persons living with Alzheimer’s disease from a middle‐income country
Authors: Cominetti Marcia Regina , Pedroso Renata Valle , Victoriano Pedro Henrique Moreira , de Sousa Danilo Barroso , Palma Leticia Fernanda , Grigoli Marina Mantellatto , Popolin Cecilia Patricia , da Silva Vanessa Alexandre , de Oliveira Sabrina Dorta , Manzine Patricia Regina , Pelegrini Lucas Nogueira de Carvalho 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers are gaining attention lately, and recent evidence supports the potential role of ADAM10 as an Alzheimer’s disease (AD) biomarker. However, most available information on these biomarkers comes from high‐income countries, where the population is usually highly educated. The influence of years of education (YoE) and older age on cognitive performance is well described in the literature, and they are risk factors for dementia. Therefore, in this study, we aim (1) to analyze whether education mediates the relationship between age and cognitive performance even among those with few YoE and (2) to compare plasma levels of ADAM10 in healthy controls (HC) and persons living with AD (PLwAD).MethodsIn this cross‐sectional and analytical study, participants (n=81) were low‐educated older adults from a middle‐income country (Brazil) and were assigned into two groups: HC (n=37) and PLwAD (n=44). The Mini‐mental State Examination (MMSE) evaluated cognitive performance. SDS‐Page and Western‐Blotting were used to obtain plasma levels of ADAM10.ResultsParticipants’ mean age and YoE were 75.5 (7.9) and 4.9 (3.5) respectively. PLwAD patients were older (t=‐4.67; p<0.0012), had fewer YoE (t=3.53; p=0.002), performed worse in MMSE (t= 1.72; p<0.001), and had higher levels of ADAM10 in plasma (t=‐2.24; p=0.31). The mediation analysis suggested a total effect of age on MMSE score of ‐0.366 (p<0.001; 95%CI [‐0.53 to ‐0.20]), a direct effect of age (controlling for YoE) on MMSE score of ‐0.302 (p<0.001; 95%CI [‐0.47 to ‐0.13]) and an indirect effect of age on MMSE score, via YoE, of ‐0.0803 (95%BCaCI [‐0.18 to ‐0.01]). Finally, the logistic regression analysis suggested that higher levels of plasma ADAM10 increase the probability of being diagnosed with AD (Exp(B) = 2.099; 95% C.I. for Exp(B) [1019 to 4.321]).ConclusionOur results suggested that education mediates the effect of age on cognitive performance, even among those with fewer YoE. Also, higher levels of ADAM10 in plasma are associated with AD diagnosis. These findings hold significance as they offer a distinctive perspective from a middle‐income country with diverse demographics, potentially shaping future research and informing healthcare strategies in analogous settings.
Experiences recruiting from neighborhoods based on area deprivation index (ADI)
Authors: Russ Eunji , Kind Amy J.H. , Gillen Daniel L , Witbracht Megan G. , Ritchie Marina , Duran Edwin , Grant‐Freeman Zion T , Medina Melany , Grill Joshua D 
Published: January 2025

AbstractBackgroundFew interventions have demonstrated efficacy for increasing diversity in Alzheimer’s disease (AD) clinical research and fewer still have targeted disadvantaged neighborhoods specifically. As part of a larger study to test recruitment strategies into the UC Irvine Consent‐to‐Contact Registry (C2C), we qualitatively assessed experiences of conducting community‐based outreach throughout disadvantaged neighborhoods in Orange County, California.MethodWe are conducting an interrupted time series design to test recruitment interventions, stratified by Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. The experiment tests Facebook advertisements, mailed postcards, and in‐person outreach. We report the experiences of in‐person outreach in diverse neighborhoods in the first year of outreach for a two‐year study. We used the ADI to characterize the location of 223 Orange County community‐based organizations, including, 36 churches, 42 senior centers, 47 libraries, and 98 other venues. Outreach events at community‐based organizations or other venues were targeted across ADI quintiles during the first week of every study period. Our diverse team of research staff, faculty, community Speaker’s Bureau members, and undergraduate volunteers were trained to conduct outreach in the community to provide education on brain health and information about research opportunities via resource tables and educational presentations.ResultSince February 2023, we have conducted 30 events (14 presentations and 16 tables). Seven events were provided in a non‐English language (i.e., Spanish, Korean, Mandarin, and Vietnamese). We reached 205 people from tabling and 359 from presentations. Among 564 individuals reached, n = 33 provided information to register for the registry on site and n = 18 registered for a specific research study. Twenty‐two individuals reported difficulty in registering for the registry due to the absence of an email address, unfamiliarity with QR codes, or the need for family assistance to complete online forms (64% of these were from the two highest ADI quintiles). Site‐specific barriers included lack of media equipment, promotional support from site, and space for outreach.ConclusionIdentifying barriers to effective community‐based outreach in diverse neighborhoods will be important to developing strategies in improving brain health communication and research on recruitment of underrepresented communities.
Impact of a Timely Diagnosis of Early Alzheimer’s Disease on Functional Outcomes
Authors: Briesacher Becky A , Zhang Ning A , Juday Timothy R , Frech Feride H , Batrla Richard 
Published: January 2025

AbstractBackgroundThe National Plan to Address Alzheimer’s Disease (AD) prioritizes timely diagnosis of mild cognitive impairment (MCI) as one of its key goals. Studies describing the downstream consequences of not having a timely diagnosis in this vulnerable population are limited. The study objective will evaluate the relationship between a timely MCI diagnosis and decline in functional outcomes compared to a missed diagnosis.MethodThis observational study utilizes 2008‐2020 data from the Health and Retirement Study (HRS), a longitudinal panel study that surveys a representative sample of 20,000 people age >50 years in the US every 2 years. Our study is research in progress; final data will extend through 2022. Cognition was assessed by a validated tool, Telephone Interview for Cognitive Status (TICS). A timely diagnosis of MCI is defined as a self or proxy report of a healthcare provider diagnosis in the HRS within 2 years of an MCI‐qualifying score on the TICS. Survival analyses will be used to assess longitudinal change every two years between diagnosed and missed diagnosis groups.ResultPreliminary analyses identified a study population of 4712 patients with an MCI‐qualifying score; 303 (6.4%) reported a timely MCI diagnosis. Ongoing analyses will shed light on the impact of a timely MCI diagnosis on functional outcomes.ConclusionFinal analyses will clarify results and provide an indication of the impact of a timely MCI diagnosis on functional outcomes.
Associations between peripheral blood DNA methylation and FDG‐PET signal in AD individuals
Authors: Perquim Lavinia , de Bastiani Marco Antônio , Machado Luiza Santos , Borelli Wyllians Vendramini , Povala Guilherme , Schlickmann Thomas Hugentobler , Pascoal Tharick A. , Rosa‐Neto Pedro , Cristino Alexandre Santos , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundEpigenetics plays a crucial role in regulating genetic transcription and responding to environmental and lifestyle changes without altering the DNA sequence. Their dysregulation is associated with AD, presenting potential as blood biomarkers. However, no study has evaluated whether peripheral blood (PB) epigenetic biomarkers are associated with brain metabolism, indexed by FDG‐PET, a classic Imaging AD biomarker. Thus, we explore the associations between PB DNA methylation and FDG‐PET signal in the brain of cognitively unimpaired (CU) and AD individuals.MethodWe evaluated CU=43 and AD=122 individuals from the ADNI cohort who underwent FDG‐PET imaging and PB DNA methylation analysis. Methylation data were analyzed using the minfi R package. Correlation analysis was performed with the statistically significant differentially methylated regions (DMRs) (p<0.005) and the regional FDG‐PET standardized uptake value ratio (SUVRs) values extracted with the DKT atlas. Voxel‐wise associations between FDG‐PET and DMRs were tested using linear regressions accounting for group, gender, age, and APOE4 status. The analysis was corrected for multiple comparisons using cluster‐wise RFT (p<0.05).ResultWe identified 478 DMRs (Figure 1), multiple of them significantly associated with regional FDG‐PET SUVRs (Figure 2). The voxel‐based analysis demonstrated that DMR cg02041677, located in the ATE1 gene, was negatively associated with FDG‐PET signal in the left hippocampus, right orbitofrontal gyrus, and right medial temporal gyrus (tmax=‐4.28, ‐4.04, ‐3.58, respectively; p‐value<0.001). The cg11128212, in the intron, nearby two lncRNA (ENSG00000289046, ENSG00000274591), was positively associated with brain metabolism in the left hippocampus, left temporal pole, and left middle temporal gyrus (tmax=4.08, 3.98, 3.80, respectively; p‐value<0.001) while the cg11901271, located in intron, nearby of a LncRNA (ENSG00000287358), showed positive correlations with FDG‐PET in the Left hippocampus (tmax=5.35, respectively; p‐value<0.001) (Figure 3).ConclusionHere, we show that PB DMRs exhibited a significant pattern of association with brain glucose metabolism in vulnerable AD regions. LncRNAs are important transcriptional regulators, the methylation could impact gene expression in AD and present potential as blood biomarkers.
Hyperbaric Oxygen therapy for older adults with T2D and Mild Cognitive Impairment ‐ A baseline characteristics
Authors: Benari Ori , Ravona‐Springer Ramit , Sano Mary , Bendlin Barbara B. , Livny Abigail , Almog Ganit , Leroith Derek , Beeri Michal S 
Published: January 2025

AbstractBackgroundHyperbaric oxygen therapy (HBOT) is a treatment in which oxygen‐enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute and is approved for the treatment of T2D ischemic wounds. Type 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Evidence small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogenesis, leading to cognitive improvement.MethodWe have conducted a double blind, placebo controlled, clinical trial on brain and cognitive outcomes in elderly with T2D and mild cognitive impairment (MCI) to compare the effects of HBOT vs. sham. This analysis reports the baseline characteristics of those recruited.ResultA total of 155 participants, comprising 69% males (mean age 71.26) and 31% females (mean age 70.23), met the eligibility criteria to commence hyperbaric oxygen therapy (HBOT) with a Total Clinical Dementia Rating (CDR) of 0.5, Mini‐Mental State Examination (MMSE) score greater than 23, and no contraindications for HBOT. The average MMSE score was 28.5 for males and 28.4 for females. Beck’s Depression Inventory (BDI) revealed a mean score of 5.1 for males and 6.1 for females. Notably, 119 participants exhibited impairment in the CDR memory domain (CDR > 0) and other associated domains.ConclusionRecent studies have indicated that hyperbaric oxygen therapy (HBOT) can stimulate neuroplasticity and enhance cognition in individuals recovering from strokes and traumatic brain injuries. However, the impact of HBOT on cognition in patients with Type 2 Diabetes (T2D) who are at a high risk of dementia remains to be established. The outcomes of this study, if successful, could furnish compelling evidence regarding the potential benefits of HBOT on brain function and cognition within this distinctive patient population.
“A combined potential biomarker candidate and drug target quantified using Single Molecule Array ‐ GFAP and NFL implication in the progression of Dementia.”
Authors: Anwar Masroor , Dey Sharmistha , Dey Aparajit Ballav , Lee Jinkook 
Published: January 2025

AbstractBackgroundThe lack of knowledge about the onset and progression of dementia hampers its early diagnosis and possible treatment leading to severe condition like Alzheimer’s disease. Technological advancement like new brain network modeling tools might provide insight into the disease progression but a broader view of the biochemical changes induced by dementia in an early and pre‐symptomatic stage needs to be explored. Therefore, a multicentric longitudinal study was designed to quantify proteins molecules associated with cognitive impairment.MethodWe measured the levels of four protein molecules Aβ1‐42, Aβ1‐40, GFAP, and NfL in plasma of 1619 participants comprising of 14% (Alzheimer’s Disease) AD patients, 39% (Mild cognitive impairment) MCI patients and 47% Geriatric controls (GC). The quantitative measurement was performed using flexible, robust, and ultra‐sensitive immunoassay platform SIMOA (Single Molecule Array). Statistical significance was defined as p < 0.05. All statistical analyses were performed in the Prism ver. 5.03 program (GraphPad Software Inc, La Jolla, CA, USA).ResultThe comparative analysis showed plasma protein concentrations of NFL and GFAP were significantly higher in AD and MCI patients compared to GC group (p < 0.001) whereas no significant difference was observed for Aβ1‐42 and Aβ1‐40. Interestingly gender wise analysis of NFL showed the concentration difference between GC versus AD was significantly higher in female compared to male (concentration difference Male; 23.78pg/mL Female; 3.47pg/mL). NFL and GFAP exhibited higher correlation with increasing age. Concentration of GFAP significantly increased in all the three age groups (60‐70years p<0.01, 71‐80years p<0.001, 81years and above p<0.0001) in AD patients compared to GC.ConclusionWe showed a correlation between a profile of four plasma protein biomarkers in development and progression of dementia patients. Our findings indicate that higher plasma NFL and GFAP expression may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.
What happens next? Repeated administration of a social and structural determinants of health questionnaire in an Alzheimer’s Disease Research Center
Authors: Stites Shana D. , Humphreys Valerie , Kuz Carolyn , Schumann Rosalie , Halberstadter Kimberly , Mechanic‐Hamilton Dawn 
Published: January 2025

AbstractBackgroundSocial and structural determinants of health (SSDoH) must be measured longitudinally in order to better understand the effects of lived experiences on the trajectories of Alzheimer’s disease and related dementias (ADRD) outcomes. We repeated administration of an SSDOH survey to examine response rates and response consistency in a sample of cognitively typical older adults.MethodOne online survey and one follow‐up survey were administered to cognitively unimpaired participants (n = 135) in the UPenn Alzheimer’s Disease Research Center clinical cohort ∼1.5 years apart. The ∼225 items covered the following categories: (1) Education, (2) Economic Status and Strain, (3) Occupation, (4) Stressors and Subjective Stress, (6) Subjective Social Support and Status, and (7) Sociodemographic data, which included age, race, language, disability, neighborhood, sex, sexual orientation, and gender identity questions. We summarize pilot data on item and instrument completion rates and changes in participant responses.Result81 of 135 participants completed the follow‐up survey, which is a response rate of 60%. Most participants completed most items. The two measures with the lowest completion rates were: Calgary Charter on Health Literacy Scale (74/81) and the Perceived Stress Scale (69/81). Some participants who did not complete a given measure during the first administration did complete that measure during the second. In addition, responses on most measures, single items or multi‐item scales, varied between the administrations. Some responses appeared to change because of ambiguity in the item’s phrasing, administration process, or reflected changes over time in the constructs being assessed.ConclusionOverall, it was feasible to repeatedly administer a survey of SSDoH items to a group of cognitively unimpaired older adults. The response rate was reasonable but lower than expected in a group of volunteer research participants indicating that multiple modes of administration may be useful for increasing engagement. Differences in the data produced from repeated administration of measures was useful in identifying ambiguity in items and methods that aid in improving research rigor and reproducibility. The data are also useful in understanding the temporal stability or instability of SSDOH experiences among these research participants.
Associations between New Deal emergency employment of teachers and teachers per student with late‐life cognition among Health and Retirement Study Participants
Authors: Eng Chloe W. , Rehkopf David , Modrek Sepideh 
Published: January 2025

AbstractBackgroundHigher school quality, and decreased student‐teacher ratio in particular, is associated with improvements in late‐life cognition. New deal emergency employment programs in the 1930s provided funding for hundreds of thousands of teachers in response to sweeping school budget cuts of the Great Depression. We examine the association between increased area‐level teacher employment through the Public Emergency Work (PEW) programs and late‐life cognition.MethodBlack and White Health and Retirement Study participants (age 50+ years) were linked to 1940 census records with childhood geographic information (n = 7,726). Average z‐standardized imputed memory scores across biennial survey waves (1998‐2018; mean follow‐up: 4.4 years) were estimated as a function of census county‐level PEW teachers employed per 1,000 students, adjusting for the census county‐level ratio of full‐time teachers employed per 1,000 students. Teachers per student was calculated separately for segregated vs. non‐segregated states, with race‐specific teachers per student calculated historically de jure segregated Jim Crow states. Analyses were stratified by rurality due to contextual differences in classroom structure between rural and urban students. Mixed linear regression models with random intercepts were adjusted for individual/area‐level covariates with state fixed effects.ResultMost (76.5%) participants lived in districts with at least one PEW teacher (Figure 1). PEW teacher employment was higher in areas with more Black residents, higher unemployment, and fewer homeowners. Residence in areas with no employment of teachers through PEW was associated with a ‐0.1002 (95% CI: ‐0.1971, ‐0.0033) SD decrease in late‐life memory (Table 1). Benefits of additional PEW teachers for late‐life memory was slightly larger in areas with more existing full‐time teachers (B = 0.0006; 95% CI: 0.0001, 0.0012), and the negative association between no PEW teachers and late‐life memory was slightly attenuated in areas with more existing full‐time teachers (B = 0.0037; 95% CI: 0.0002, 0.0073; Table 2). Number of PEW teachers was not associated with late‐life memory in rural areas.ConclusionChildhood residence in urban areas that did not receive additional teacher employment through PEW programs was associated with lower late‐life memory; effects were stronger among areas with fewer existing full‐time teachers. Rural/urban discrepancies may reflect differential allocation and exposure to PEW programs.
High‐performance plasma proteomic biomarker candidates in early Alzheimer's disease
Authors: Xie Yuhan , Sun Hui , Liu Fang , Zheng Yaonan , Zhang Mang , Ma Xin , Yu Xin , zhang nan , huang chaolan , Wang Huali 
Published: January 2025

AbstractBackgroundThe present study aimed to establish a panel of plasma proteins that are associated with cognitive performance and amyloid‐β burden and establish their utility for distinguishing early Alzheimer’s disease (AD) from healthy controls.MethodPlasma from fifty patients with early AD (all amyloid‐positive) and forty‐nine healthy controls (HCs) were assayed using quantitative mass spectrometry. The weighted correlation network analysis (WGCNA) was used to explore the association between plasma protein levels and cognitive performance and filter out the high‐performance plasma proteomic biomarker candidates. Further correlation analysis was used to examine these proteins’ association with amyloid‐β burden in AD brain measured with PET imaging.ResultWe identified 1124 proteins that were dysregulated in AD plasma. Further, 22 panel proteins representative of the AD plasma protein profile were selected based on their association with the cognitive performance and cerebral regional SUVR of PiB‐PET imaging. The panel proteins, involved in the amyloid‐β protein production, metabolism and immune processes, have demonstrated high performance in distinguishing between early AD and HCs.ConclusionThis study comprehensively profiled the AD plasma proteome and identified 22 dysregulated proteins as high‐performance biomarker candidates for early Alzheimer’s disease.
Gut Microbiome Multi‐Omics and Cognitive Function in a Large Latino Cohort
Authors: Palacios Natalia , Gordon Scot , Wang Tao , Huttenhower Curtis , Gonzalez Hector M , Knight Rob , Decarli Charles , Daviglus Martha L , Lamar Melissa , Tarraf Wassim , Cai Jianwen , Burk Robbie , Qi Quibin , Kaplan Robert C. 
Published: January 2025

AbstractBackgroundFew large microbiome studies on Alzheimer’s Disease and Related Dementia (AD/ADRD) have been conducted, especially among US Latinos. We conducted a study within the Study of Latinos‐ Investigation of Neurocognitive Aging (SOL‐INCA) cohort to examine the role of the gut microbiota in cognitive function.MethodsWe analyzed the fecal metagenomes of 2,470 SOL‐INCA participants to, cross‐sectionally, identify microbial taxonomic and functional features associated with cognitive function. Global cognition was defined as an aggregate score based on a cognitive battery (executive function, working memory, among others). Omnibus (PERMANOVA) and feature‐wise analyses (MaAsLin2) were conducted to identify microbiome‐cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition. We assessed the accuracy of a Random Forest classifier to distinguish SOL participants with the best (>=1SD above mean) vs. the worst (>=1SD below mean) cognition. We also tested the association of identified taxa and KEGG modules with concurrently collected serum metabolites.ResultWe identified several taxa and pathways significantly associated with cognitive function in SOL. B. longum was the taxa most strongly associated with worse cognition, whereas Eubacterium species (E. siraeum and E.eligens), were associated with better cognition. Several KEGG modules, most strongly Ornithine and Serine biosynthesis, were associated with worse cognition. A microbiome species‐based Random Forest classifier had moderate accuracy (AUC = 0.62) to discriminate between high (1SD or more above mean) vs low (1SD or more below mean) cognition.ConclusionIn a large Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition, further implicating the microbiome in AD/ADRD risk.