bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct ABCA7 high‐risk allele modulates medial temporal lobe dynamic network flexibility among cognitively healthy older African Americans
Authors: Arnasalam Alyssa , Sheikh Mustafa , Budak Miray , Piaszczynska Wiktoria , Oyono Arcande , Perez José Mojica , Fausto Bernadette A. , Gluck Mark A. 
Published: January 2025

AbstractBackgroundThe medial temporal lobe (MTL) is the earliest region to display atrophy in Alzheimer’s disease (AD)1. Apolipoprotein E (APOE‐ε4) and ABCA7‐80 (rs115550680), two genes involved in lipid metabolism, are the strongest heritable contributors to AD in African Americans2. However, the longitudinal influence of these genes on MTL dynamic network flexibility, a novel neuroimaging marker of preclinical AD, is unknown. This study investigated the influence of APOE‐ε4 and ABCA7‐80 high‐risk alleles on MTL dynamic network flexibility longitudinally among cognitively healthy older African Americans.Method135 participants (Age≥60, Meanbaseline age = 68.07, SDbaseline age = 7.31, Meaneducation = 13.56, SDeducation = 2.99) from the longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University–Newark, completed saliva collection for genotyping and ≥1 neuroimaging visits across 4 years. Associations between APOE‐ε4 and ABCA7‐80 on MTL dynamic network flexibility across time were assessed using linear mixed models.ResultAt baseline, the APOE‐ε4 allele had no significant relationship with MTL Dynamic Network Flexibility (ß = 0.034, p = 0.297), whereas ABCA7‐80 was significantly associated with MTL Dynamic Network Flexibility (ß = ‐0.124, p = 0.003). The ABCA7‐80 x time interaction was significantly associated with MTL Dynamic Network Flexibility (ß = ‐0.074, p = 0.029), while there was no such significant ApoE‐ε4 x time interaction (ßApoE*Instance = ‐0.017, pApoE*Instance = 0.53).ConclusionThere were baseline and longitudinal differences on MTL dynamic network flexibility between ABCA7‐80 but not APOE‐ε4 risk groups among cognitively healthy older African Americans. ABCA7‐80 may have greater influence than APOE‐ε4 in the early MTL network changes associated with AD risk in older African Americans.
Enhancing Early Detection of Mild Cognitive Impairment Using Preprocessed Connected Speech and Natural Language Processing
Authors: Lu Chingching , Wang Pei‐Ning 
Published: January 2025

AbstractBackgroundEarly detection is crucial for the timely intervention and management of dementia, potentially slowing its progression. Early stages of dementia might only subtly affect communication, yet connected speech analysis can detect these minor anomalies. Cognitive tests involving connected speech, like the Boston Diagnostic Aphasia Examination’s (BDAE) “cookie‐theft” picture description task, are pivotal in detecting dementia. However, previous research typically treats their responses as a whole.MethodThis study preprocesses connected speech from the “cookie theft” task to facilitate AI‐driven detection improvements. We analyzed narratives from 54 normal subjects, 26 with MCI, and 38 with Alzheimer’s Disease (AD), focusing on nine major concepts to quantify accuracy across groups.ResultDifferences in concept accuracy were significant even among normal individuals. A detailed analysis revealed that concepts 3 and 1 were particularly effective in differentiating between normal individuals and those with cognitive impairments, and between MCI and AD. Concepts 2, 3, and 7 were crucial for distinguishing between normal and MCI subjects. Concepts 4, 5, 8, and 9 showed no discriminatory power.ConclusionAdvances in technology, particularly in natural language processing (NLP), allow for the automated analysis of connected speech. It can provide quick and reliable assessments. By categorizing and preprocessing speech data before AI analysis, our approach enhances the model’s predictive accuracy for early‐stage dementia detection. It can also help for developing more diagnostic images and cognitive training exercises. Furthermore, it does not require expensive equipment or invasive procedures, making it accessible for widespread use in various settings, including community centers and primary care, and particularly beneficial for regular monitoring.
Patterns in NIA Health Disparities Research Framework Domains and AD‐Plasma Biomarkers
Authors: Vassilaki Maria , Aakre Jeremiah A , Castillo Anna M , Lesnick Timothy G. , Kremers Walter K. , Algeciras‐Schimnich Alicia , Graff‐Radford Jonathan , Knopman David S. , Mosley Thomas H. , Windham B Gwen , Griswold Michael E. , Lowe Val J. , Jack Clifford R. , Petersen Ronald C. , Vemuri Prashanthi 
Published: January 2025

AbstractBackgroundThe NIA Health Disparities Research (NIA‐HD) Framework organizes factors in four domains (i.e., environmental, sociocultural, behavioral, and biological), which work together over the lifetime to influence health and health disparities.MethodIn previous work, we employed a 2‐stage approach using factor and principal component (PC) analyses to identify patterns of factors in the domains of the NIA‐HD Framework. We found three PCs that identified related groupings from more than one NIA‐HD domain. PC1: retirement status, residence type, multivitamin use, heart disease, Charlson comorbidity index, walking/balance difficulties, and Beck Depression Inventory (BDI)‐II questions – mainly from the somatic dimension; PC2: physical activity/exercise, social and group activities, education, occupation, cardiometabolic risk factors, and self‐rated health; PC3: national and state area deprivation index ranking and BDI‐II questions – mainly in the cognitive dimension. Age and sex‐adjusted linear regression models were used to assess the cross‐sectional association of each PC with AD‐plasma biomarkers measured using the Quanterix Simoa platform in the Mayo Clinic Study of Aging (MCSA) participants. AD‐plasma biomarkers included Aβ 42/40, phosphorylated‐tau 181 (p‐tau181), plasma glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). All analyses were considered statistically significant at a p <0.05.ResultThere were 1300 cognitively unimpaired participants, 50 years old or older, with available plasma biomarkers (mean age (SD) 68.6 (9.5) years; 49.1% were female) at the current study baseline. PC1 and PC3 were associated with higher NfL and p‐tau 181 values (p<0.05). PC1 and PC2 were associated with higher GFAP values (p<0.05). No PCs were associated with the Aβ 42/40 ratio. Findings were mostly similar after additionally adjusting for global cognitive performance and chronic kidney disease.ConclusionWe found that patterns in a wide range of environmental, sociocultural, behavioral, and biological factors were associated with AD plasma biomarkers. Longitudinal studies are warranted to validate findings and support multi‐faceted approaches to address health disparities and achieve disease delay and prevention.
Developing an anatomically valid segmentation protocol for anterior regions of the medial temporal lobe
Authors: Sadeghpour Niyousha , Lim Sydney A , Wuestefeld Anika , Denning Amanda E , Ittyerah Ranjit , Trotman Winifred , Chung Eunice , Sadaghiani Shokufeh , Prabhakaran Karthik , Bedard Madigan , Ohm Daniel T , Artacho‐Perula Emilio , Martin Maria Mercedes Iniguez de Onzono , Munoz Monica , Romero Francisco Javier Molina , González José Carlos Delgado , Jimenez Maria del Mar Arroyo , Rabal Maria del Pilar Marcos , Sanchez Sandra Cebada , Prieto Carlos de la Rosa , Insausti Ricardo , McMillan Corey T , Grossman Murray , Lee Eddie B , Detre John A. , Trojanowski John Q , Tisdall M. Dylan , Irwin David J , Wolk David A , Yushkevich Paul A. , Wisse Laura E.M. 
Published: January 2025

AbstractBackgroundThe anterior portion of the MTL is one of the first regions targeted by pathology in sporadic Alzheimer’s disease (AD) indicating the potential for imaging metrics from this region to serve as valuable imaging biomarkers. However, most existing automated approaches for MTL segmentation do not incorporate anterior MTL subregions, and the few that do fail to account for its complex anatomical variability. Leveraging a unique postmortem dataset consisting of histology and structural MRI scans we aimed to develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 and apply it for automated MTL segmentation of in vivo 3 tesla (T) MRI.MethodWe included 20 cases between 61 to 97 years of age (50% females) with and without neurodegenerative diseases (11 vs. 9 cases) to ensure broad generalizability of the developed protocol. Postmortem digitized MTL Nissl‐stained coronal histology serial sections from these cases were registered to same‐subject 0.2×0.2×0.2‐mm3 9.4T postmortem MRI and annotated by an expert neuroanatomist. To develop the segmentation protocol, we determined the location of the histological borders of interest in relation to anatomical landmarks observable on in vivo MRI. The protocol was first applied manually to 29 3T in vivo MRI scans and then used to train an automatic segmentation method T1‐ASHS (Automatic Segmentation of Hippocampal Subfields). Intra‐rater reliability of a manual rater and five‐fold cross‐validation accuracy of T1‐ASHS were assessed with the Dice Similarity Index (DSI).ResultSegmentation rules for the borders of ERC, BA35 and BA36 based on systematic analysis of inter‐landmark distances on histological sections are shown in Figure 1. Intra‐rater reliability for the manual rater applying these rules to 15 in vivo 3T MRI scans was high (Table‐1; Figure‐2). Comparing manual segmentations with the automated ones generated by T1‐ASHS showed moderate reliability, reflecting the challenging anatomy of this region. However, segmentation accuracy for the whole MTL including the newly added region was comparable to the previously reported accuracy for MTL without this region (Table‐1).ConclusionFuture work will examine trhe utility of morphometric measures of anterior MTL regions enabled by this protocol for early AD.
Neurotransmitter‐related functional connectivity alterations associated with cognitive decline in people with mild cognitive impairment and mild Alzheimer’s disease
Authors: Venneri Annalena , Manca Riccardo 
Published: January 2025

AbstractBackgroundEarly alterations in the ventral tegmental area, a major brainstem dopaminergic nucleus, may be a marker of Alzheimer’ disease (AD). However, how dopamine (DA) may influence neurofunctional and cognitive decline due to AD remains elusive. The aim of this study was to investigate alterations in resting‐state functional connectivity (FC) associated with DA distribution in the brain along the AD continuum.MaterialsEighty‐six older adults with mild cognitive impairment (MCI), 58 with mild dementia due to AD and 76 cognitively unimpaired (CU) participants of the multicentre VPH‐DARE@IT project were included. Participants underwent comprehensive clinical, neuropsychological and MRI assessmentsMethodsFunctional MRI data were pre‐processed by using the REACT pipeline to obtain FC maps informed by DA receptor and transporter PET/SPECT atlas for the whole brain and for the nigrostriatal and mesocorticolimbic pathways. Whole‐brain FC maps informed by acetylcholine (ACh) were also extracted for comparison. A cognitive composite score (Cog‐CS) was calculated as the average of neuropsychological test z‐scores. Between‐group differences in neurotransmitter‐informed FC were assessed using ANCOVA models in SMP12. Moreover, the association between FC maps and both Cog‐CS and episodic memory scores was investigated in the whole sample. Age, education, sex, total intracranial volume and recruitment site were included as covariates.ResultsThe AD group showed mesocorticolimbic DA‐related FC decline in the bilateral precuneus, and increase in the thalamus, while the MCI group showed nigrostriatal FC decline in the left superior temporal gyrus. ACh‐related FC decline was observed in both MCI and AD, compared with CU, in fronto‐parietal and temporal areas. The Cog‐CS was positively associated with ACh‐related FC only in posterior cingulate, temporal and cerebellar areas. Episodic memory performance was correlated positively with ACh‐ and DA‐related FC in occipito‐parietal areas and negatively with DA‐related FC in thalamic and fronto‐temporal areas.ConclusionsFC alterations associated with both Ach and DA may be sensitive to cognitive decline due to AD. These findings, first of this kind, may offer useful insights to test recently proposed hypotheses on the involvement of these neuromodulatory systems in driving AD‐related neuropathological changes as well as to investigate the mechanisms of action of novel treatments.
Exploring the Mediating Role of Social Participation in Reducing Caregiver Burdens in Dementia Care
Authors: Bae Suyeong , Hong Ickpyo 
Published: January 2025

AbstractBackgroundThe increasing global incidence of dementia is accompanied by rising burdens for caregivers, who face physical and emotional challenges such as depression and pain. Existing research primarily explores the negative impacts of caregiving on quality of life, health, and finances, alongside the benefits of social support and specific programs. However, such approaches might be relatively passive. Our study aims to examine the mediation effect of social participation between caregivers and their burdens. We expect the study finding could be used as an active strategy that significantly alleviates caregiver burdens.MethodWe used the data of caregivers and recipients from the 2022 National Health and Aging Trends Study and National Study of Caregiving IV. The dependent variables were self‐reported questionnaires that assess physical and emotional burdens. Social participation was used as a mediator, and the independent variable was whether the caregiver cared for recipients with dementia or not. Structural equation modeling was utilized to investigate the mediating role of social participation in the relationship between caregivers and the physical and emotional burdens they experience.ResultThe final sample was 1,836 caregivers, and they consisted of 595 males (32.41%) and 1241 females (67.59%). The model fit value indicated that the model fits the data (chi‐square value = 322.795, df = 60, p‐value = 0.000; RMSEA = 0.049; CFI = 0.938; TLI = 0.919; SRMR = 0.043). The caregivers who care for recipients with dementia were negatively associated with social participation (standardized coefficient = −0.114, p‐value <.0001). Social participation was negatively associated with the physical and emotional burden (standardized coefficient = −0.230, p‐value <.0001; standardized coefficient = −0.208, p‐value <.0001, respectively). There were no significant direct paths between caregivers who care for recipients with dementia and physical burden, emotional burden each other.ConclusionThe study findings can help recognize the role of social participation in the caregivers who care for recipients with dementia by understanding the positive effect of social participation. In addition, the findings suggest that social participation can reduce the physical and emotional burden of caregivers who care for recipients with dementia.
Deferoxamine treatment decreases amyloid fibrils and lowers iron mediated oxidative damage in ApoEFAD mice
Authors: Thorwald Max A , Godoy‐Lugo Jose A , Christensen Amy , Pike Christian J. , Forman Henry Jay , Finch Caleb E 
Published: January 2025

AbstractBackgroundIron is implicated in Alzheimer’s disease (AD) and is bound to β‐amyloid (Ab) plaques. AD brains have increased 4‐hydroxynonenal (HNE) adducts, a lipid decomposition product bound to proteins originating from iron mediated lipid peroxidation. Increased brain iron may result from cerebral microbleeds which by nature are rich sources of iron. In EFAD aging, microbleeds arise before amyloid plaque formation, suggesting a role for microbleeds in plaque formation. We hypothesize that treatment with the iron chelator Deferoxamine (DFO) would reduce brain iron and attenuate oxidative damage from these microbleeds.Method6‐month female EFAD mice were treated with DFO (10mg/kg/day) by diet (2 weeks; n = 9) or intraperitoneal injection (1 week; n = 11) and compared to untreated (n = 8). Cerebral cortex was assayed for soluble Aβ peptides, insoluble Aβ fibrils, and HNE by dot blot. Antioxidants were measured by Western blot or GPx assay (Cayman Chemical).ResultDFO in diet or by IP decreased insoluble fibrillar amyloid by 50% with corresponding 2‐fold increases in soluble Aβ monomers Aβ40 and ‐42. DFO reduced HNE levels by 50%; nitrotyrosine, a non‐iron dependent oxidation marker, remained unchanged. Protection from lipid oxidation is mediated by GPx4 or GSTA4, which DFO increased by 50%. These measures were complimented with 25% increases in total GPx activity by DFO.ConclusionDFO solubilized fibrillar Aβ and increased Aβ monomers. Furthermore, DFO increased antioxidants critical to the protection against microbleed‐induced oxidative damage. These findings are substantiated by the decrease in HNE. Future studies will examine combination therapy with Aβ monoclonal antibodies which may liberate bound iron from Aβ plaques.
D13 caspase‐6‐cleaved tau, a new biomarker to complement Alzheimer’s disease diagnosis
Authors: Rizzi Liara , Rojas Julio C. , Ambrose Andrew J. , Balthazar Marcio Luiz Figueredo , Arkin Michelle R. , Grinberg Lea T. 
Published: January 2025

AbstractBackgroundCaspase‐cleaved tau can critically be involved in the pathogenesis and progression of Alzheimer’s disease (AD), due to its ability to promote both misfolding and neurodegeneration, which ultimately leads to progressive cognitive impairment. Neuropathological studies show that caspase‐cleaved tau species are abundant in AD brain neurons, yet show only a modest degree of co‐occurrence with phospho‐tau. This suggests that caspase‐cleaved tau is an overlooked form of tau pathology that is related to the vulnerability and pathogenesis of AD.MethodWe developed a homebrew Simoa immunoassay for detecting N‐terminal D13 caspase‐6‐cleaved tau in the cerebrospinal fluid (CSF). For developing the assay, we used a neo‐epitope monoclonal antibody developed and validated by our group and used in previously published histological work. After optimization, we tested this assay in a pilot study with a discovery cohort comprising CSF samples from 20 subjects with mild to moderate dementia and positive for AD biomarkers and 20 well‐characterized healthy controls (HC).ResultThe signal translated in the mean average enzymes per bead was significantly higher in Alzheimer’s disease cases compared to healthy controls (0.01640 vs. 0.01189, ρ < 0.001). There were no significant differences in demographics such as age (ρ = 0.072) or gender (ρ = 0.723) between the two groups.ConclusionWe introduce the initial D13 caspase‐6‐cleaved tau biomarker immunoassay for quantitatively assessing caspase‐cleaved tau pathology in CSF. This assay offers the chance to identify pathological tau that conventional p‐tau assays may overlook, potentially enhancing the assessment of clinical trials. We are currently expanding the study cohort and correlating the findings with metrics from p‐tau biomarkers.
Impact of Aerobic Cycling on Affective Symptoms and Quality of Life in Persons Experiencing Subjective Cognitive Decline
Authors: Watry Rebecca Ann‐Maria , Hadidi Niloufar , Kreitzer Mary Jo , Bhimani Rozina , Yu Fang , Salisbury Dereck L. 
Published: January 2025

AbstractBackgroundTransition to subjective cognitive decline (SCD), and dementia is often accompanied by increased affective symptoms (i.e., anxiety and depression), which increase the risk of Alzheimer’s dementia and decreased quality of life (QoL). The hazard ratio of SCD with affective symptoms is significantly worse in comparison to SCD only. A paucity of research investigates the impact of treatments, including aerobic exercise, on SCD, affective symptoms, and QoL. The purpose was to examine the preliminary efficacy of moderate‐intensity cycling exercise versus control on SCD, affective symptoms, and overall QoL, including QoL domains.MethodsThe Exergames Study randomized community‐dwelling older adults with SCD (n = 38) to 12 weeks (36 sessions) of exergames, cycling only, and stretching control groups using a 2:1:1 allocation ratio. For this secondary data analysis, the exergames and cycling groups were combined (n = 30). SCD symptoms, affective symptoms, and QoL were assessed by the SCD‐Q, GAS‐10, GDS‐SF, and WHOQOL‐BREF. Between‐group change was evaluated by ANCOVA, and relationships between changes in QoL were calculated with multiple linear regression, adjusting for baseline values.ResultsEnrollment was from November 2019 ‐ December 2021. The mean age was 74.6 (7.4) years old and 69% were female (Table 1). There were no significant between‐group changes (Table 2). Large and moderate between‐group effect sizes were seen in favor of the stretching group for WHOQOL‐BREF Social domain (between group change = 1.90 [1.19], ηp2 = 0.19); GAS‐10 (between group change = ‐5.36 [0.29], ηp2 = 0.11); and WHOQOL‐BREF Physical Domain (between group change = 4.56 [4.40], ηp2 = 0.10). Increased affective symptom scores by one item corresponded with a decrease in predictive QoL scores (anxiety‐physical health ‐0.52 [0.25], p = 0.05; depressive‐overall ‐3.01 [1.10], p = 0.01; depressive‐psychological ‐1.19 [0.36], p < 0.01; Table 3).ConclusionAlthough non‐significant, between‐group changes favored the control group. Changes in affective symptoms predicted changes in QoL. The participation attention received by this secluded population of older adults and COVID‐19 losses likely impacted results. Further research with larger groups (that does not span a pandemic) is necessary to elucidate the full impacts of aerobic cycling on SCD symptoms, affective symptoms, and QoL.