bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intersections of sex and racialization on ATV(N) biomarkers
Authors: Shaaban C. Elizabeth , Reese Alexandria C. , Royse Sarah K. , Snitz Beth E. , Karikari Thomas K , Hengenius James , Huppert Theodore , Roush Rebecca E. , Cisneros Geraldine , Potopenko Katey , Becker James T , Cohen Annie 
Published: January 2025

AbstractBackgroundDifferences in Alzheimer’s disease (AD) amyloid, tau, vascular, and neurodegeneration (ATV(N)) biomarkers by sex and racialized group have been reported, but little is known about the intersections of sex and racialization on these biomarkers.MethodsParticipants in this cross‐sectional analysis are from the Connectomics of Brain Aging study, a Human Connectome Project protocol evaluating brain structure and function in aging and AD. We measured A using global amyloid SUVR from 11C‐PiB PET, T using plasma p‐tau 217, V using lobar unhealthy white matter connectivity (UWMC), a novel measure indicating the proportion of WM connections impacted by white matter hyperintensities (WMH), and N using cortical thickness from an AD‐based meta‐region of interest. We tested for intersectional effects of sex and racialized group on ATV(N) biomarkers in robust regressions by testing models with and without sex*racialized group interaction terms.ResultsThe sample included N=202 participants with the following characteristics: age, 62 years; female sex, 67%; Black racialization, 50%; education, 14 years; APOE4+, 31%; cognitively impaired, 27%; Table 1. In robust regression models we found that women had significantly more amyloid and frontal UWMC, and less tau and parietal and occipital UWMC than men; participants racialized as Black had significantly more temporal lobe UWMC and significantly less occipital lobe UWMC, amyloid, tau, and cortical thickness than participants racialized as white (Table 2). Intersectional effects were found only for parietal lobe UWMC (p for interaction=0.03; Table 2), such that men racialized as Black had the greatest parietal UWMC, while men and women racialized as white did not vary in their parietal UWMC (Figure 1). Results with lobar WMH instead of UWMC were similar.ConclusionOur results confirm ATV(N) biomarker differences by sex and racialized group. They suggest that men racialized as Black may be uniquely at risk for UWMC in the parietal lobe but found no intersectional effects on other biomarkers. Future work will investigate specific WM tracts involved in the parietal UWMC and associated risk factors such as structural and social determinants of health as well as cardiovascular risk factors and comorbidities.
Exposure to Structural Sexism at Birth is Associated with Faster Late‐Life Memory Decline Among Black and White Women in the U.S.
Authors: Avila Justina F , Adkins‐Jackson Paris AJ , Hill‐Jarrett Tanisha G , Brickman Adam M. , Schupf Nicole , Mayeux Richard , Manly Jennifer J. 
Published: January 2025

AbstractBackgroundStructural determinants of health may be important drivers of late‐life cognitive decline and dementia risk for women who have a disproportionate burden of Alzheimer’s disease (AD). This study examines how early life exposure to structural sexism influences cognitive trajectories among women racialized as Black and White.MethodThis study analyzed longitudinal data from two cohort studies: the Washington Heights‐Inwood Columbia Aging Project (WHICAP) and the Health and Retirement Study (HRS). Eligible participants were aged 60+, US born, non‐Latinx, and dementia‐free at their baseline cognitive assessment. Confirmatory factor analysis produced a latent variable of state‐level structural sexism comprised of 6 US Census‐derived indicators representing sex/gender disparities in access to economic, political, cultural, and reproductive health resources. Latent variable scores, per US state, were generated for each year between 1902 ‐ 1954 and linked with WHICAP and HRS participants using birth year and state. Cognitive outcomes were level and change in memory performance. Stratified mixed‐effects models were used to examine associations between structural sexism and memory trajectories across women and men. Interaction terms were included to examine associations by racialized group.ResultExposure to higher levels of structural sexism was associated with lower baseline memory performance among WHICAP women and a more rapid rate of memory decline among women in both studies. For women, the difference in rate of memory decline between being born in the state with the highest structural sexism versus the state with the lowest structural sexism was equivalent to 8 to 9 years of cognitive aging. Associations between structural sexism and baseline memory were stronger among Black women compared with White women for both studies.ConclusionThis study provides some of the first insights into the relationship between structural sexism and late‐life cognitive aging outcomes. Results suggest that, among US‐born Black and White women, early‐life exposure to structural sexism negatively impacts late‐life memory trajectories. Structural determinants are actionable risk factors that can be modified through policy changes. A deeper understanding of the pathways linking structural sexism to AD risk can inform the development of future policy interventions to improve late‐life cognitive health among women.
The Modifying Effects of Sex, Race, and Social Relationships on the Association between White Matter Integrity and Dementia Risk: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study
Authors: Eswaran Surabhee , Gottesman Rebecca F. , Knopman David S. , Koton Silvia , Kucharska‐Newton Anna M. , Liu Albert C. , Liu Chelsea , Lutsey Pamela L. , Mosley Thomas H. , Palta Priya , Sharrett A. Richey , Sullivan Kevin J. , Walker Keenan A. , Groechel Renee 
Published: January 2025

AbstractBackgroundWeakened white matter (WM) integrity is highly associated with dementia risk. Still, not everyone with WM changes develops dementia, suggesting the important role modifiable lifestyle factors may have in reducing dementia risk. We investigated how social relationships in mid‐life may modify the association between WM integrity and incident dementia risk within race and sex subgroups.MethodIn 1,679 Atherosclerosis Risk in Community (ARIC) study participants who were dementia‐free in mid‐life, psychosocial health was assessed via self‐reported questionnaires and participants were classified as having strong or poor social relationships in mid‐life (visit 2: 1990‐1992). Through diffusion tensor imaging, WM integrity was evaluated with 3T brain MRI (visit 5: 2011 – 2013); fractional anisotropy (FA) and mean diffusivity (MD) were estimated. Incident dementia cases were identified from visit 5 through December 31, 2019, with ongoing surveillance. Relative contributions of social relationships and WM integrity to incident dementia were evaluated in Cox‐proportional hazard regression models with race and race‐sex as interaction terms, and in stratified models (White Females, Black Females, White Males, Black Males).ResultSignificant three‐way interactions were observed between race, WM integrity, and mid‐life social relationships (p‐interaction<0.01). In Black participants with strong mid‐life social relationships, higher MD (hazard ratio (HR): 0.93, 95% CI: 0.63 – 1.38) and lower FA (HR: 1.25, 95% CI: 0.84 – 1.86) were not associated with the risk of dementia, although in Black participants with poor social relationships, higher MD remained a significant risk factor for dementia. However, across all White participants, higher MD and lower FA were associated with the risk of dementia, regardless of mid‐life social relationships (Table 1; Figure 1). Analysis of three‐way interactions between race‐sex, WM integrity, and mid‐life social relationships suggested that effect modification by mid‐life social relationships was most evident in Black Females, respective to other groups (Table 2; Figure 1).ConclusionThe contribution of WM integrity to dementia risk may be lower in Black participants with strong social relationships in mid‐life, particularly in Black Females. Further understanding of how contextual social factors may influence brain health in diverse populations should be examined in future studies and intervention efforts.
Intersectionality of Gender and Social Determinants of Health in Asymptomatic Alzheimer’s Neuropathology
Authors: Besser Lilah M , O'Shea Deirdre , Fuentes Anthony J. , Galvin James E 
Published: January 2025

AbstractBackgroundStudies are limited regarding the role of intersectional social determinants of health in asymptomatic Alzheimer’s disease neuropathology (ADNP).MethodWe analyzed data on 3,107 participants in the National Alzheimer’s Coordinating Center’s Neuropathology Dataset who had a visit ≤24 months before autopsy and confirmed ADNP (moderate to frequent neuritic plaques and Braak Stage III‐VI). Groups were defined based on the presence (symptomatic ADNP, n = 2,956) or absence (asymptomatic ADNP, n = 151) of an MCI/dementia diagnosis at the final visit before death. Social determinants included gender (man/women), educational attainment (years), racialized group (Black, White, other), Hispanic ethnicity, living alone, and English/non‐English primary language. Multivariable logistic regression tested associations between these determinants and ADNP classification (asymptomatic vs symptomatic), and additionally, the models were stratified by gender. Models controlled for age at death, apolipoprotein e4 carrier status, informant‐reported memory decline, time between last visit and autopsy, vascular and Lewy body pathology, and comorbidities (i.e., hypertension, diabetes, depression).ResultsWomen (versus men) were more likely to have asymptomatic ADNP (OR = 1.02, 95% CI = 1.00‐1.03), as were those with greater years of education (OR = 1.004, 95% CI = 1.004‐1.006), Hispanic individuals (OR = 1.07, 95% CI = 1.03‐1.11), and those living alone (OR = 1.11, 95% CI = 1.06‐1.17). Non‐English primary language speakers were less likely to have asymptomatic ADNP (OR = 0.88, 95% CI = 0.85‐0.92). Gender‐stratified analyses showed that both women and men were more likely to have asymptomatic ADNP if they were Hispanic (women: OR = 1.07, 95% CI = 1.02‐1.11; men: OR = 1.04, 95% CI: 1.00‐1.08) or living alone (women: OR = 1.12, 95% CI = 1.07‐1.18; men: OR = 1.10, 95% CI: 1.02‐1.18). Women speaking a non‐English primary language were less likely to have asymptomatic ADNP (OR = 0.87, 95% CI: 0.83‐0.91), while in men, more years of education was associated with greater odds of asymptomatic ADNP (OR = 1.004, 95% CI: 1.002‐1.007).ConclusionOur study suggests that gender, education, Hispanic ethnicity, primary language, and living alone, as well as the intersectionality of these factors with gender, may differentially influence MCI/dementia diagnosis prior to death in the presence of ADNP. These findings emphasize the need for future Alzheimer’s disease research to prioritize intersectional social determinants of brain health.
Factors associated with caregivers’ perceptions of advance care planning for people living with dementia
Authors: Zhang Yuchen , Sereika Susan M , Lingler Jennifer H , Seaman Jennifer , Pettigrew Corinne , Albert Marilyn S. 
Published: January 2025

AbstractBackgroundPeople living with dementia (PwD) experience progressive functional decline with increasing dependence on their caregivers. Advanced care planning (ACP) has the potential to promote quality of life, reduce iatrogenic harm, and minimize overutilization of healthcare resources, yet planning ahead in the context of dementia is challenging and requires consideration of numerous factors over an extended period of time. We examined caregivers’ perceptions of current and end‐stage medical care preferences in PwD and the impact of ACP‐related discussions between caregivers and PwD.MethodThis secondary analysis utilized data from the cross‐sectional survey, “Care Planning for Individuals with Dementia”, which was administered by staff at Alzheimer’s Disease Centers across the U.S. Statistical analysis employed binary, ordinal, and multinomial logistic regression. Predicting variables included caregivers’ knowledge about dementia; outcome variables were caregivers’ perceptions of PwD’s goals of medical care; covariates were relationships between caregivers and PwD, the Clinical Dementia Rating of PwD, and demographic characteristics.ResultCaregivers were mainly white (88.5%) and highly educated (mean = 15.9 years), with a mean age of 78.3 years and high dementia knowledge scores (mean = 8.4/10). Caregivers’ knowledge about dementia was associated with their perceptions about PwD’s medical care. Caregivers with higher total dementia knowledge scores had 1.32 times the odds of endorsing comfort care at end‐stage dementia (p = 0.009). Greater knowledge about severe dementia was inversely associated with perceiving the need for further discussions (knowing a lot: OR = 0.17, p<0.001; knowing some things: OR = 0.37, p = 0.006). Caregivers of PwD in earlier stages were less likely to endorse comfort care as their current preference (no impairment & MCI: OR = 0.17, p<0.001; mild: OR = 0.36, p<0.001), and caregivers of patients with no or mild impairment had 5.24 times the odds of indicating the need for further discussions of treatment preferences (p = 0.02) than caregivers of severe stage patients. Lastly, if caregivers already had ACP‐related conversations with PwD, they were 2.67 times more likely to prefer comfort care for end‐stage disease (p = 0.007).ConclusionOur analyses show the importance of providing early dementia‐specific education for PwD and their caregivers on end‐of‐life care. Our findings also highlight ACP as a dynamic and continuous process throughout the disease course.
Inflammatory and Redox Blood Gene Expression Fingerprint of Obstructive Sleep Apnoea in Patients with Alzheimer’s Disease
Authors: ElKhayat Leila Romero , Dakterzada Faride , Huerto Raquel P , Carnes Anna , Targa Adriano , Barbe Ferran , Milanesi Elena , Cuadrado Antonio , Piñol‐Ripoll Gerard 
Published: January 2025

AbstractBackgroundObstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer’s disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA.MethodWe included 40 AD patients diagnosed based on clinical manifestations and AD biomarker levels in cerebrospinal fluid (CSF). Severe or nonsevere OSA (apnoea–hypoapnoea index ³ 30/h and < 30/h, respectively) was diagnosed through overnight polysomnography (PSG). The expression levels of 136 inflammation‐related and 84 redox‐related genes were evaluated by whole blood targeted transcriptomics.ResultWe identified three inflammatory genes and six redox genes that were upregulated in AD patients with severe OSA. Of all upregulated genes, TNFSF14 and ALOX12 (inflammatory and redox genes, respectively) were positively correlated with the arousal index. GSR, a redox gene, was positively correlated with the AHI (p<0.05). Finally, we found good correlations between the three inflammatory genes and six redox genes (p<0.05). A pathway enrichment analysis showed a strong enrichment of the serotonergic synapse pathway in severe OSA AD patients.ConclusionOur results show an upregulation of nine genes involved in NF‐κB‐mediated inflammation and redox metabolism in the blood of patients with mild AD with severe OSA. Therefore, OSA may worsen the inflammation and oxidative damage that are already altered in patients with AD.
Relationship between Posterior Resting‐State Electroencephalographic Alpha Rhythms and Cerebrospinal Fluid Biomarkers of Neuropathology in Patients with Alzheimer’s Disease Mild Cognitive Impairment
Authors: Percio Claudio Del , Lizio Roberta , Lopez Susanna , Noce Giuseppe , Jakhar Dharmendra , Carpi Matteo , Arnaldi Dario , Güntekin Bahar , Yener Görsev , Babiloni Claudio 
Published: January 2025

AbstractBackgroundPatients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) are characterized by abnormalities in resting‐state electroencephalographic (rsEEG) rhythms as measures of brain neural synchronization dysfunction (Babiloni et al., PMID: 33860614). Here, we tested the two following hypotheses that those rsEEG abnormalities: (i) may be higher in ADMCI patients than in patients with MCI not due to AD (noADMCI); and (ii) may be related to the AD diagnostic amyloid‐tau biomarkers derived from cerebrospinal fluid (CSF).MethodDatasets in 70 ADMCI patients, 45 patients noADMCI, and 45 normal elderly (Healthy) participants originated from a Eurasian archive. The eyes‐closed rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta and gamma bands. The eLORETA freeware estimated rsEEG cortical sources.ResultStatistical results showed: (i) compared with the Healthy group, the posterior alpha rsEEG source activities were more reduced in the ADMCI group than in the noADMCI group (p < 0.001; Figure 1); (ii) in the ADMCI group, a strong negative correlation between the CSF phospho‐tau levels and the occipital alpha rsEEG source activities was observed (r = 0.4, p < 0.001; Figure 2). Interestingly, in the ADMCI group, no correlation between the CSF and magnetic resonance imaging (MRI; neurodegeneration) variables was observed.ConclusionIn ADMCI patients, the abnormalities of cortical neural synchronization mechanisms underpinning brain arousal and vigilance are related to the AD diagnostic phospho‐tau biomarkers and precede a similar relationship between AD amyloid‐tau and neurodegeneration biomarkers. Remarkably, the amyloid‐tau‐neurodegeneration (ATN) AD model may be enriched with those pathophysiological ‘P’ biomarkers as revealed by rsEEG rhythms.
Amyloid and tau PET as well as functional connectivity mediate the association between APOEε4 and neurodegeneration
Authors: Zhang Bing , Xu Xinru 
Published: January 2025

AbstractBackgroundIt remains unclear to what extent APOEε4 relates to amyloid beta (Aβ) and tau deposition, functional connectivity and neurodegeneration in Alzheimer's disease spectrum.MethodIn 345 participants including subjective cognitive impairment and mild cognitive impairment and Alzheimer disease, We investigate the association of APOEε 4 with Aβ and Tau, functional connectivity and neurodegeneration (cortical thickness and gray matter volume). Using mediation analyses, we tested the indirect effects of APOEε4 on neurodegeneration via Tau deposition (18F‐AV451 positron emission tomography) and interregional functional connectivity (functional MRI) in Braak I‐II and Braak III‐VI.ResultWe observed that increased APOEε4 dose was associated with poorer neurodegeneration in AD typical regional, with the strongest effects observed for medial temporal lobe gray matter atrophy. These relationships were mediated mainly via tau pathology, particularly of the medial parietal lobe, and to a lesser extent serially mediated via Aβ and functional activities in AD signature regions.ConclusionIn summary, our finding highlight a pathway in which APOEε4 affects neurodegeneration via increased tau pathology and reduced functional connectivity in critical lobe. Examining APOE ε4‐related brain changes through the use of neuroimaging biomarkers in the Alzheimer's disease spectrum provides a unique opportunity to advance our knowledge of the underlying pathophysiology of AD, particularly in the stage of subjective cognitive decline (SCD).
Mapping between the Mini‐Mental State Examination and the Clinical Dementia Rating scale for Patients with Alzheimer’s Disease: An External Validation Study
Authors: Brogaard Niels Juul , Hahn‐Pedersen Julie Hviid , Gundgaard Jens , Polavieja Pepa , Bray Benjamin D , Chan Mei Sum , Hoang Men , Araya Daniel , Trepel Dominic 
Published: January 2025

AbstractBackgroundThe Clinical Dementia Rating scale Sum of Boxes (CDR‐SB) measure is commonly used in specialist research settings and clinical trials. In clinical practice, shorter cognitive assessments, such as the Mini‐Mental State Examination (MMSE), are commonly used. A targeted literature search identified existing MMSE – CDR‐SB mappings; such as Balsis et al. 2015 and Perneczky et al. 2006. However, neither mapping provided granular translation of these measurements across all Alzheimer’s disease (AD) stages. This study therefore aimed to extend and externally validate existing published mappings between the MMSE and CDR to support the translation of measurements between these tools across all AD stages.MethodThe optimal functional form for the mapping was investigated using power‐transformed univariate regressions, and the modelled mapping was extended to capture the full range of AD stages. External validation of the mapping was conducted using the US National Alzheimer’s Coordinating Centers (NACC) database, stratified by age, sex, education, and AD medication use. Individuals’ most recent visit with valid MMSE and CDR‐SB scores, and concordant AD staging based on clinical diagnoses and global CDR scores were included. Calibration and discrimination metrics were reported, following best practice guidelines for clinical prediction tool validation.ResultA linear MMSE to CDR‐SB mapping (see Figure 1 for equation) was found to have the optimal functional form and demonstrated high goodness of fit (Adjusted = 0.989). When externally validated on the NACC population (n = 25,768; Table 1), the mapping satisfied all validation metrics (Somers’ D = 0.705, R2 = 0.739; above the prespecified 0.7 threshold), and deciles of patients by CDR‐SB were generally well‐calibrated (Figure 1). The mapping also demonstrated acceptable discrimination between no/mild AD dementia versus moderate AD dementia (AUC = 0.885; 95%CI: 0.879‐0.891) and between moderate AD dementia versus severe AD dementia patients (AUC = 0.756; 95%CI: 0.743‐0.769). The mapping accurately predicted AD stage across the overall NACC database and when stratified by subgroups (Table 2).ConclusionThis extended mapping for MMSE to CDR‐SB demonstrated good performance, especially in less severe AD stages. The findings can support the translation of AD severity assessments between datasets using CDR‐SB and MMSE, bridging a common information gap between clinical trials and real‐world evidence studies.
Eye movement combined machine learning methods for three‐classification diagnosis of Alzheimer's disease
Authors: Song Jiaqi , Yu Weihua , Lü Yang 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) is a chronically progressive neurodegenerative disease, and mild cognitive impairment (MCI) is a transitional stage between normal cognition and AD. Multi‐classification of AD poses a challenging task, and currently, only a few algorithms have achieved an accuracy above 60%. This study was designed to construct a diagnostic model based on eye movement parameters to distinguish dementia due to AD, MCI and normal cognition.MethodEye movement data were collected from 258 subjects, comprising 66 individuals with normal cognition, 81 patients with MCI and 111 patients with dementia due to AD. Machine learning methods were used to construct classification models. Pearson's correlation analysis was used to detect correlations between the five most important eye movement indicators and neuropsychological scales.ResultAmong all the machine learning classifiers, the gradient boosting classifier model demonstrated the best classification performance, achieved 68.2% of accuracy and 66.32% of F1‐score. Additionally, correlation analysis indicated that the eye movement parameters exhibited a significant correlation with various cognitive functions, including general cognitive status, attention, visuospatial ability, episodic memory, language and instrumental activities of daily life.ConclusionEye movement parameters in conjunction with machine learning methods achieve satisfactory overall accuracy, making it an effective and less time‐consuming method to assist clinical diagnosis of AD.