bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maya Angelou Center for Health Equity Caregiver College (MC2): Focus Group Feedback from Tier 1 and Tier 3 Counties in North Carolina
Authors: Caban‐Holt Allison M. , Fortune Doreen Rone , Sanderlin Ashley H. , Whitaker‐Brown Charlene , Artis Ruby Tonnette , Starks Takiyah D. , Lloyd Shawnta , Gregory Ashley , Byrd Goldie S. 
Published: January 2025

AbstractBackgroundBlack/African American (AA) caregivers of patients with Alzheimer’s disease (AD) and related disorders can play a critical role in maintaining patient health. AD caregivers who face economic challenges may have less access to resources that may reduce caregiver burden they experience. The North Carolina Department of Commerce ranks the state’s 100 counties based on economic well‐being and assigns the most distressed counties as Tier 1, and least distressed as Tier 3. Focus groups were conducted to determine the needs of Black/AA AD caregivers in a Tier 1 and a Tier 3 county.MethodThe Maya Angelou Center for Health Equity Caregiver College (MC2) is an educational program that aims to improve informal caregivers’ knowledge of AD. Focus groups were conducted with community stakeholders in Wilson (Tier 1) and Mecklenburg (Tier 3) counties in North Carolina. Focus group attendees were engaged in discussion on topics including a review of local resources to support caregiving, challenges that AD caregivers face, educational needs of caregivers and preferred format of an MC2 event.ResultFocus group participants (N = 15; Wilson = 8, Mecklenburg = 7) are African American (100%), with professional and community roles including clergy, caregivers, nursing, teaching, manager, community health worker, and local city officials. Findings suggest that significant needs in a Tier 1 county include lack of geriatric∖AD specialists, few caregiver support resources, and little qualified in‐home care assistance. In a Tier 3 county, structural barriers and physical access to resources were named as difficulties. Common issues for both counties included confusion by what insurance plans cover. The design for MC2 was requested as a 1‐day format in the Tier 3 County because of a large population of working caregivers, whereas in the Tier 1 County a multi‐day MC2 format was recommended due to the perception that people in the county would benefit more from a more intensive AD educational event.ConclusionNeeds in Tier 1 and Tier 3 counties differed, however, both groups need help navigating medical insurance. Results will be used to customize the MC2 events to meet the expressed needs of the stakeholders in each county.
Investigating intimate partner violence as a dementia risk factor through co‐creation of research design and knowledge translation deliverables with survivors and sector partners
Authors: Wellington Cheryl L 
Published: January 2025

AbstractBackgroundApproximately 30% of women worldwide experience intimate partner violence (IPV). Although as many as 92% report impacts to the head and/or strangulation that raise clinical suspicion of brain injury (BI), there are no evidence‐based methods to document IPV‐BI in this vulnerable population, no clinical practice guideline, and insufficient understanding about long‐term risks including Alzheimer’s Disease and Related Dementias (ADRD). Although traumatic brain injury (TBI) is an established ADRD risk factor, little is known about attributable risk of ADRD due to IPV in either military or civilian populations. Our study aims to improve diagnosis of BI in survivors of IPV in a manner sensitive to the needs of this vulnerable population, and to raise awareness of the importance of considering IPV‐BI as a potential ADRD risk factor.MethodsWe were recently approved by the USA Department of Defence to launch a prospective observational study that leverages collaborative research at three clinical sites in British Columbia Canada that reach ethnically and geographically diverse participants. We will assess acute and chronic plasma biomarkers as diagnostic tools and will also use an integrated knowledge translation (iKT) framework including community participation to deliver a living clinical practice guideline for IPV‐BI and trauma‐informed guidance for ADRD researchers to specifically ask about IPV in clinical history.ResultsThus far, we have worked with multiple stakeholders to co‐create a novel Case Report Form suitable for use in real‐life clinics to collect IPV history including head impact and strangulation events, and have pilot data on several plasma biomarkers relevant to ADRD that, for some cases, suggest IPV may lead to accelerated brain aging and biomarker patterns consistent with AD.ConclusionsWe will discuss how extensive feedback from persons with lived experience and stakeholder groups was essential to design a feasible community‐based study, as common data elements now almost routine in ADRD and TBI studies needed to be reworked to consider the unique needs of IPV survivors in participating in research.
Basal Ganglia Mechanical Stiffness is Associated with Fluid Intelligence in Amnestic Mild Cognitive Impairment
Authors: Kramer Mary K , Delgorio Peyton L , Diano Alexa M , McIlvain Grace , Twohy Kyra E , Bailey Olivia M , Cohen Matthew L. , Lanzi Alyssa M , Martens Christopher R. , Johnson Curtis L 
Published: January 2025

AbstractBackgroundMagnetic resonance elastography (MRE) is an MRI technique that uses mild, externally applied vibrations to quantify the mechanical properties of tissues in vivo. MRE measures, such as stiffness, have been shown to be sensitive to changes in brain health with aging and neurodegeneration. Here we used MRE to characterize differences in brain mechanical properties between individuals with amnestic mild cognitive impairment (aMCI) and cognitively unimpaired subjects (CU).MethodA cohort of 67 cognitively unimpaired subjects (21M/46F; 60‐82y) and a cohort of 34 subjects with aMCI (11M/23F; 60‐89y) completed an MRE scan to assess their brain mechanical properties. From this, we quantified basal ganglia (BG) stiffness in each subject including the caudate, pallidum, putamen, and nucleus accumbens. Subjects also completed the NIH toolbox cognition battery from which we examined fluid cognition composite score, which reflects logic and reasoning skills.ResultWe found a significant group difference in stiffness of the basal ganglia (BG). Interestingly, aMCI subjects had significantly higher BG stiffness than CUs (2.99 vs. 2.89 kPa, p<0.05; Figure 1). Within the aMCI group, BG stiffness was positively correlated with fluid cognitive score (r = 0.48, p<0.01; Figure 2), where higher scores were associated with greater stiffness; the same relationship in the CU group was not statistically significant.ConclusionHigher BG stiffness found in the aMCI group may reflect aspects of aMCI pathology and progression that MRE can sensitively detect. Most MRE studies report that healthy brains are associated with higher stiffness than those with neurodegenerative pathology, with our previous work showing that aMCI participants had softer hippocampi than age‐matched CUs (Delgorio, 2023). Our findings in the BG are surprising in this context but may indicate a compensatory mechanism that occurs during early progression of aMCI and results in increased stiffness, which was previously suggested by Murphy (2016). Here we also provide the first evidence that higher BG stiffness in aMCI is associated with better cognitive function, which further points to higher stiffness being compensatory rather than pathological. The neurobiological basis of this compensatory increase in BG stiffness of aMCI subjects requires further study but could be influenced by acute neuroinflammatory processes.
Hippocampal Functional Organization Mediates the Impact of the Cortical Iron on the Cognition in Women with Suspected Coronary Microvascular Dysfunction
Authors: Silemek Arzu C Has , Wertheimer Jeffrey C , Wei Janet , Dumitrascu Oana M , Kremen Sarah , Xie Yibin , Li Debiao , Nelson Michael D , Tan Zaldy S , Merz Noel Bairey , Sati Pascal , Gao Wei 
Published: January 2025

AbstractBackgroundWomen with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer’s disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain’s functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).Material and MethodsTwenty‐seven women with suspected CMD [Age; median (range) = 54 (29‐76)], drawn from ongoing cohorts (3R01HL146158‐04S1,3U54AG065141‐04S1), underwent a 3T MRI protocol, including submillimeter T2* 3‐dimensional echo‐planar‐imaging for assessing iron deposition with high‐resolution quantitative susceptibility mapping (QSM) and resting‐state fMRI (rs‐fMRI). Iron content was quantified by total‐generalized‐variation based QSM analysis. Functional integrity was determined via graph theoretical approach (i.e., nodal degree). Cognitive assessment was also performed using the NIH Toolbox. Mediation analysis was conducted using Python Statsmodels.ResultsMost of the women with suspected CMD showed lower performance in processing speed, working memory, executive function, and attention (Figure‐1A). We found a significant association between elevated iron levels in paracentral gyrus and lower functional connectivity in left hippocampus (p = 0.005, adjusted‐r2 = 0.19) (Figure‐1B). Elevated iron level in the paracentral gyrus showed an impact on cognitive performance in the domains of executive function and attention (p<0.0001, coefficient = 531.09) as well as language functions and crystalized abilities (p = 0.036, coefficient = 362.45), mediated by functional connectivity in the left hippocampus (indirect effect on executive function / language: p = 0.034 / 0.038, coefficient = ‐254.54 /‐ 213.06) (Figure‐1C).ConclusionsOur results suggest that changes in hippocampal functional organization are associated with cortical iron deposition and mediate its impact on cognitive performances. These changes may increase the risk of cognitive decline/ADRD or in women with suspected CMD. Future research in a larger cohort with a longitudinal design is necessary to validate and expand upon these findings.
Sex‐specific risk profiles associated with Alzheimer’s disease markers in cognitively unimpaired older adults
Authors: Touron Edelweiss , Wirth Miranka , Binette Alexa Pichet , Demnitz‐King Harriet , Collette Fabienne , Poisnel Géraldine , Vivien Denis , la Sayette Vincent De , Marchant Natalie L , Chételat Gael , Gonneaud Julie 
Published: January 2025

AbstractBackgroundDespite evidence that sex can modulate Alzheimer’s disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men.MethodWe included 135 cognitively unimpaired older adults ( = 65 years old, 83 women; Table 1) from the Age‐Well trial (NCT02977819; baseline data) with multidomain assessments of modifiable risk factors, including cardiovascular (body mass index, systolic blood pressure, LDL cholesterol), lifestyle (complex mental activity throughout life, physical activity, diet), and psychological (quality of life, depressive and anxiety symptoms, rumination, worry). AD markers included the Preclinical Alzheimer Cognitive Composite‐5 (PACC‐5), a measure of global cognition sensitive to AD‐related decline, and multimodal neuroimaging and blood sampling providing measures of hippocampal volume (MRI), brain perfusion in temporo‐parietal regions, neocortical amyloid burden (PET) and p‐tau181 (plasma). Multivariate partial least squares analyses were used to assess relationships between combinations of risk factors and AD hallmarks (cognition, neurodegeneration, amyloid and tau) in women and men separately.ResultIn women, a combination of lower quality of life and complex mental activity throughout life and higher levels of anxiety and worry, was associated with lower PACC‐5 scores and higher p‐tau181 levels (p = .002, 60.5% of variance explained; Fig.1). In men, two significant latent variables emerged. Lower systolic blood pressure, adherence to a Mediterranean diet and quality of life, and higher levels of anxiety and worry, were associated with higher hippocampal volume and lower brain perfusion in regions sensitive to AD (p = .022, 45.2% of the variance explained; Fig.2A); while lower levels of quality of life and complex mental activity throughout life were associated with worse PACC‐5 scores and higher neocortical amyloid deposition and p‐tau181 levels (p = .023, 35.9% of the variance explained; Fig.2B).ConclusionThese preliminary findings suggest that the modifiable factors that could influence AD markers may differ by sex in cognitively unimpaired older adults. Pending replication in larger and independent cohorts, these results highlight the need to consider sex specificities in prevention strategies.
Comparison of cerebrospinal fluid and plasma oxidative stress biomarkers
Authors: de la Colina Adrian Noriega , Charisis Sokratis , Ntanasi Eva , Mamalaki Eirini , Skaperda Zoi , Kouretas Demetrios , Scarmeas Nikolaos 
Published: January 2025

AbstractBackgroundNumerous studies have highlighted the role of oxidative stress in Alzheimer's disease (AD) development. Yet, the alignment of systemic and central oxidative stress biomarkers is unclear across diverse populations in the AD continuum. This study aims to assess protein damage levels in plasma and cerebrospinal fluid (CSF) within the AD continuum.MethodsOne hundred forty participants without clinical dementia (47 with Mild Cognitive Impairment [MCI] and 93 cognitively unimpaired) from a memory clinic cohort underwent examination for central (CSF) and systemic (plasma) markers of oxidative stress. We measured Total Antioxidant Capacity (TAC), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and reducing power (RP) using standard laboratory techniques and absorbance spectrophotometry (Hitachi U‐1500). Pearson’s correlations were employed to determine the congruence between the same biomarkers of oxidative stress in CSF and plasma. Factor analysis was performed to ascertain how many antioxidant dimensions they represent.ResultsTable 1 outlines participants' baseline characteristics. Pearson’s correlation analysis for the entire sample revealed no congruence between CSF and plasma in TAC (r=+.087) and GSH (r=.‐.161), while CSF and plasma RP (r=.+385*) and TBARS (r=‐.216*) were correlated (Figure 1). Upon analyzing group‐level data, the cognitively unimpaired group showed congruence between CSF and plasma for GSH (r.=‐.279*) and TBARS (r=‐.287*) but not for TAC (r=+.191) and RP (r=+.202). In the MCI group, only RP (r.=+.640*) demonstrated congruence between CSF and plasma. Factor analysis with CSF biomarkers identified two components in the whole sample (Figure 2). Dimension 1= GSH, and Dimension 2=TAC, TBARS, and RP. Factor analysis with plasma identified as well two components: Dimension 1=RP and GSH, Dimension 2=TBARS and TAC. The factor analysis for the MCI group revealed the presence of a single component for CSF biomarkers, while there were two components for plasma: Dimension 1=RP and TBARS, Dimension 2=TAC and GSH.ConclusionOxidative stress biomarker patterns differ across the AD continuum. RP demonstrates the most reliability, while TAC is the least. GSH and TBARS plasma and CSF measurements are negatively associated in the cognitively unimpaired, but not in the MCI population. Understanding oxidative biomarker evolution can enhance our comprehension of their role in AD and age‐related disorders.
Synergic effect of tau tangles and cortical thinning on cognitive decline in aging and Alzheimer's disease
Authors: Trudel Lydia , Therriault Joseph , Rahmouni Nesrine , Aumont Etienne , Wang Yi‐Ting , Servaes Stijn , Macedo Arthur C. , Chan Tevy , Arias Jaime Fernandez , Hall Brandon J , Hosseini Seyyed Ali , Socualaya Kely Monica Quispialaya , Mathotaarachchi Sulantha , Stevenson Jenna , Lussier Firoza Z , Gauthier Serge , Pascoal Tharick A. , Rosa‐Neto Pedro 
Published: January 2025

AbstractBackgroundTau burden has been found to be involved in brain atrophy during aging, especially in regions such as the parahippocampal gyrus. However, how tau levels at baseline are associated with trajectories of tau accumulation, cortical thinning and cognitive impairment remains poorly understood. The goal of this study was to assess tau rate of change in patients between baseline Tau+ and Tau‐ patients. We also aimed to determine if tau status at baseline or rate of accumulation of tau interacted with the rate of cortical thinning of the parahippocampal regions, leading to an increased rate of change in cognition.MethodWe assessed 133 participants from the TRIAD cohort (mean age = 68.5 ± 8.9, 85 females) with at least two visits with tau‐PET using [18F]MK6240 and cortical thickness extracted using FreeSurfer 7. Average time between visits was 25.6 months. Patients were classified according to clinical status, Amyloid‐ß status and tau status at baseline (CU AB‐Tau‐, CU AB+Tau‐, CU AB+Tau+, MCI AB+Tau‐, MCI AB+Tau+, AD AB+Tau+). The tau‐PET rate of change was calculated for each participant, voxelwise and with temporal meta‐ROI. The MMSE rate of change was calculated to quantify cognitive decline over follow‐up period. We assessed the voxelwise relationship between baseline tau status and tau‐PET rate of change.ResultsWe found a voxelwise positive association between rate of accumulation of tau and tau status at baseline in both anterior temporal lobes. Furthermore, we found an interaction effect between tau‐PET at baseline and parahippocampal rate of atrophy on MMSE rate of change (standardized ß = 0.48, p < 0.0001).ConclusionOur results suggest that tau status at baseline might impact the rate of accumulation of tau, and that higher baseline levels of tau interact with cortical thinning of parahippocampal regions, leading to faster rates of cognitive decline. Our results emphasize the importance of preventing tau burden to prevent faster pace of cognitive decline during the disease’s trajectory.
Automated Brain Volumetry Analysis for Differential Diagnosis of Frontotemporal Dementia Subtypes
Authors: Cho Hyeonwoo , Park Mina , Lee Seung Hyun , Jung Wooseok , Kim Dong‐Hee , Kim Jinyoung , Lee Yeha 
Published: January 2025

AbstractBackgroundClinical diagnosis of frontotemporal dementia (FTD) can be challenging, requiring an accurate tool dedicated to this diagnostic hurdle. Since FTD exhibits distinct regional atrophy patterns on magnetic resonance imaging (MRI), AI‐aided automated brain volume analysis could enhance the clinical diagnostic assessment of FTD, including the detection of the disease and the classification of subtypes, which encompass behavioral variant (BV), semantic variant (SV), and progressive non‐fluent aphasia (PNFA). In this study, we leverage automated brain volumetry software to approach both FTD detection and the differential diagnosis among its subtypes.MethodA total 258 patients with FTD (BV = 57, SV = 40, PNFA = 34) and 127 Normal Control (NC) were identified from the frontotemporal lobar degeneration neuroimaging initiative (NIFD) data sets with available MRI. We obtained 104 areas of patient’s normalized regional brain volumes using VUNO‐Med DeepBrain. Comparative analyses were conducted to explore differences in regional volume distribution between FTD and NC, as well as among FTD subtype based on their known atrophy patterns. Additionally, regional normative percentiles were utilized as features for classification using the XGBoost algorithm to distinguish FTD vs NC, BV vs SV vs PNFA, and BV vs SV vs PNFA vs NC.ResultIn BV, significant differences in atrophy patterns were observed in the frontal lobe, demonstrating an anterior‐posterior gradient compared to SV, PNFA and NC (P<0.01). SV exhibited left side dominant asymmetric atrophy, particularly in the inferior temporal lobe, compared to BV, PNFA, and NC (P<0.01). Additionally, the inferior horn of the lateral ventricle in SV had higher volume than other subtypes, attributable to atrophy of surrounding brain regions. In contrast, the differences in atrophy patterns for PNFA were statistically less significant when compared to other FTD subtypes. Automated brain volumetry software‐based classifications demonstrated high accuracy of FTD vs NC (Accuracy 95% CI = [0.88, 0.89]), BV vs SV vs PNFA ([0.79, 0.81]), and BV vs SV vs PNFA vs NC ([0.82, 0.83]).ConclusionOur study demonstrates the effectiveness of automated brain volumetry and machine learning in identifying FTD and differentiating frontotemporal dementia subtypes, contributing to an enhanced understanding of subtypes and improved diagnostic precision in neurodegenerative disorders.
Associations of load and progression of imaging markers of microvascular lesions and neurodegeneration with odor identification decline: a population‐based study
Authors: Oltra Javier , Kalpouzos Grégoria , Ekström Ingrid , Larsson Maria , Qiu Chengxuan , Laukka Erika J 
Published: January 2025

AbstractBackgroundOlfactory deficits are predictive of cognitive decline and dementia. Previous studies have linked brain magnetic resonance imaging markers of neurodegeneration to olfactory deficits in aging; however, these studies analyzed cross‐sectional data for markers, olfaction, or both. Furthermore, potential cerebrovascular contributions to understanding why olfactory deficits predict dementia remain unexplored. We aimed to examine whether markers of microvascular lesions and neurodegeneration and their progression are associated with the rate of olfactory decline in community‐dwelling older adults.MethodParticipants were 405 individuals (mean age=70.2 years; 60% females) from the Swedish National study on Aging and Care in Kungsholmen (SNAC‐K) who were free from dementia at baseline. We analyzed microvascular lesions (presence of lacunes, white matter hyperintensities volume, global perivascular spaces [PVS] count) and neurodegeneration (lateral ventricular, hippocampal, and total gray matter volumes) markers, available up to 6 years and an olfactory measure (Sniffin’ Sticks odor identification task), available up to 15 years. Additionally, we assessed summary scores for microvascular lesions and neurodegeneration load (range 0–3), accounting for all markers of each category (1 point for its presence or for being in the worst quartile, as appropriate). Data were analyzed with linear mixed‐effects models.ResultAfter adjustment for sociodemographic (age, sex, and education) and extra covariates (smoking status and semantic memory), a higher global PVS count (ß =‐0.041; 95% CI, ‐0.077 to ‐0.005) and a high load (=2 points) of neurodegeneration (ß=‐0.112; 95% CI, ‐0.221 to ‐0.002) at baseline were associated with a faster olfactory decline. Longitudinally (n=228), faster accumulation of PVS (ß=‐1.812; 95% CI, ‐3.474 to ‐0.150), faster hippocampal atrophy (ß=1.348; 95% CI, 0.413 to 2.283), and an increment from low (=1 point) to high load for microvascular lesions (ß=‐0.167; 95% CI, ‐0.327 to ‐0.007) and neurodegeneration (ß=‐0.206; 95% CI, ‐0.321 to ‐0.092) were associated with an accelerated olfactory decline.ConclusionBoth microvascular lesions and neurodegeneration are longitudinally associated with olfactory decline in aging. This relationship supports the notion that olfactory deficits could be valuable as an early marker for dementia. More longitudinal studies are needed to untangle the mechanisms in play between cerebral vascular burden, atrophy, and olfaction.