bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations Between Circadian Timing and White Matter Microstructure
Authors: Weimar Lisa S , Zhang Meina , Axelson Eric , Magnotta Vincent A , Burgess Helen J , Moon Chooza 
Published: January 2025

AbstractBackgroundIndividuals with Alzheimer’s disease often exhibit white matter microstructure degenerations observable through diffusion tensor imaging (DTI). The circadian system regulates sleep and wake cycles. As people age, sleep and wake cycles can be disrupted, which can worsen sleep quality. Circadian rhythm disruption can increase the risk of developing Alzheimer’s disease and damage white matter microstructures. However, few studies have investigated the relationship between circadian timing and the structural integrity of white matter among adults.MethodData was collected from 49 later‐life adults (51% female) with mean age 70.4 years (SD = 6.50). Diffusion‐weighted MRI sequences were acquired using a 3.0T scanner. Fractional anisotropy (FA) scalar maps were generated through FSL‐DTIFIT, and the Johns Hopkins University‐ICBM white matter atlas was utilized to assess FA values within white matter tracts. Circadian timing was determined by home‐based dim light melatonin onset (DLMO). A t‐test was used to compare FA values by mean DLMO (17: 46).ResultIn this preliminary analysis later DLMO time was associated with greater FA values in the corticospinal (Meanearly DLMO = 0.41 (SD = 0.04) vs. Mean later DLMO = 0.44 (SD = 0.04), p = 0.023, uncorrected), right corticospinal (Meanearly DLMO = 0.40 (0.05) vs. Meanlater DLMO = 0.44 (0.04), p = 0.01, uncorrected), left posterior thalamic radiation (Meanearly DLMO = 0.38 (0.03) vs. Meanlater DLMO 0.40 (0.03), p = 0.048, uncorrected), cingulum‐hippocampus (Meanearly DLMO = 0.26 (0.03) vs. Meanlater DLMO = 0.28 (0.03) p = 0.025, uncorrected), and left cingulum‐hippocampus tracts (Meanearly DLMO = 0.26 (0.03) vs. Meanlater DLMO = 0.29 (0.03) p = 0.01, uncorrected).ConclusionThis preliminary data demonstrates that abnormally early circadian timing may be associated with reduced white matter integrity in specific tracts. Future research using a larger sample, longitudinal design, and multimodal imaging methods is needed to confirm these findings and identify the mechanisms underlying these associations.
Differential expression of miRNAs from circulating exosomes in Alzheimer disease and frontotemporal dementia
Authors: Orellana Paulina , Caviedes Ariel , Hernandez Hernan , Lillo Patricia , Villagra Roque , Cerda Mauricio , Zitko Pedro , Thumala Daniela , Gonzalez‐Billault Christian , Ibañez Agustin , de la Cruz Rolando , Chonchol Andrea Slachevsky , Duran‐Aniotz Claudia 
Published: January 2025

AbstractBackgroundThe content of circulating exosomes has been observed to be altered in response to changes in physiological and pathological conditions, and they are detectable in different human fluids such as blood. Studies focused on the quantification of Aβ and tau proteins, as molecules contained within exosomes, suggest that they are related with Alzheimer disease (AD) and frontotemporal dementia (FTD) development, demonstrated that plasma‐derived exosome analysis is a good approach for searching for biomarkers in the development of dementia. Our aim is to identify new blood biomarkers to detect the AD or FTD in the Chilean population using machine learning based on exosomal miRNAs.MethodmiRNAs were extracted from circulating exosomes from plasma samples of 25 healthy controls (HC), 25 AD patients and 10 FTD patients. miRNAs were sequencing to identify and measure the expression levels. Dysregulated miRNAs were analyzed to create machine learning algorithms. miRNAs obtained from algorithms were validated in a new population of subjects 30 HC, 30 AD and 10 FTD using qRT‐PCR.ResultAfter the sequencing and machine learning analysis, we identified 8 miRNAs as potential predictors of AD and FTD. These miRNAs were further assessed in new samples using the qRT‐PCR technique. We identified 4 miRNAs with variable expression in patients with AD and FTD, with three miRNAs downregulated in AD and one upregulated in FTD. For the four miRNAs, significant differences in expression are observed between AD and FTD.ConclusionThis is the first study in the Chilean population that evaluates miRNAs in patients with AD and FTD. The study of miRNAs as biomarkers of dementia provides the opportunity to develop low‐cost and easy‐to‐obtain diagnostic methods, in addition to the possibility of being implemented in a greater number of health centers, making them more accessible to the population.
Innovations in Dementia Empowerment and Action [IDEA]: First Dementia/Memory Loss RCT Intervention for Sexual and Gender Minority Older Adults and Their Care Partners
Authors: Fredriksen‐Goldsen Karen I , Kim Hyun‐Jun , Jones Brittany R , Hoy‐Ellis Charles Pitre , Oswald Austin G. , Teri Linda 
Published: January 2025

AbstractBackgroundSexual and gender minority (SGM) older adults experience disparities in subjective cognitive impairment when compared to heterosexuals of similar age. Yet, SGM older adults and their care partners living with dementia/memory loss face substantial barriers to accessing culturally relevant health and dementia care. To address the gap in culturally relevant interventions, we tested the efficacy of a first of its kind stigma reduction, cognitive behavioral intervention for SGM older adults living with dementia/memory loss and their care partners, Aging with Pride: Innovations in Empowerment and Action (IDEA). IDEA is a 6‐week, 9‐session culturally responsive intervention delivered by trained coaches built upon an efficacious dementia intervention, Reducing Disability in Alzheimer’s Disease (RDAD).MethodsUsing a 2‐arm, single‐blind randomized controlled trial with a staggered multiple baseline design, we enrolled 161 dyads of SGM older adults living with dementia/memory loss and their care partners and randomized them to either the IDEA or RDAD intervention arms. For this presentation, we tested the short and long‐term effects in exercise, physical functioning, and depression, as well as the moderating effects of social support and microaggressions. We used linear mixed models with random intercepts and slopes to analyze our longitudinal data.ResultsAmong the IDEA participants, those living with dementia/memory loss showed a significant increase in the number of days exercising post‐intervention, and care partners had decreased depression. The treatment effects for exercise among care recipients persisted at 30 weeks post‐intervention, while the treatment effects for depression among care partners persisted at both 30‐ and 52‐weeks post‐intervention. We also found moderating effects of social support and microaggressions on key outcomes.ConclusionsIDEA, designed to be culturally tailored for underserved and stigmatized populations, including SGM older adults and care partners, was found to be an efficacious intervention. The IDEA intervention is poised to be responsive to the disparities in dementia care in our increasingly diverse and growing older adult population. Recognizing the importance of cultural responsiveness and stigma reduction in dementia and caregiving interventions, the study findings will be disseminated among care providers and within underserved communities.
Early CER Strategies to Recruit Black 80+ year olds in the SuperAging Research Initiative
Authors: Timpo Phyllis , Maher Amanda Cook , Zolliecoffer Chandler , Rahman‐Filipiak Annalise , Lincoln Gabrielle A , Moore Sophia , Awosika Avemaria , Devine Rebecca , Peirce Hannah , Engelmeyer Janessa , Morhardt Darby J. , Okonkwo Ozioma C , Bruce Monica , Lose Sarah R , Goldstein Felicia , Trammell Antoine R , Locke Mary , Parker Monica W , Culum Ivan , Finger Elizabeth , Roberts Angela C , Rogalski Emily J 
Published: January 2025

AbstractBackgroundCommunity engaged research (CER) has been critical for increasing diversity in Alzheimer’s studies. However, the effectiveness of CER for engaging a diverse population of ‘SuperAgers,’ has been largely unstudied. SuperAgers are individuals age 80+ with superior episodic memory. The multi‐site SuperAging Research Initiative (SRI) seeks to recruit at least 500 SuperAgers and similarly aged controls, including 40% who identify as Black. This report summarizes initial CER strategies, implementation of new strategies, and enrollment success across the first ∼18 months.MethodSemi‐structured interviews were conducted at each site to assess current CER strategies and perceptions of facilitators/barriers to CER approaches. Interviews were transcribed and concept mapping was used to identify key themes across sites. Key themes are reported here along with recruitment outcomes across the sites over the first ∼18 months. Initial responsive actions are described.ResultSRI sites were selected based on their historical success engaging and recruiting Black older adults in cognitive aging research; however, identification and recruitment of SuperAgers was new for most sites. Results revealed strong current community engagement practices across sites. Emergent themes included prioritizing diverse staff, barriers to CER, strengths of the multi‐site design, the value of research to participants. Sites also implemented several CER strategies including building/enhancing community partnerships, providing community presentations, and engaging community members and enrolled participants in feedback sessions related to recruitment methods. Responsive actions of the SRI included development of participant informed culturally tailored recruitment flyers, videos, and photos, which incorporated site‐level feedback. Holiday‐themed appreciation gifts were provided to enrolled participants.Initial enrollment included 173 participants (mean age: 86.6 years). Diverse recruitment across sites ranged from 0‐27%. Diverse recruitment increased over the second half of the year, potentially suggesting early success with CER strategies.ConclusionInitial recruitment reflects a starting point for the enrollment of Black SuperAgers and Controls. Future plans involve implementing additional study‐wide CER recruitment methods, utilizing online registries as a recruitment source, and establishing ambassador boards to boost SRI enrollment of older Black adults. Strategy success will be carefully quantified, and outcomes will be shared for future research use.
Associations between obesity, AD pathology, and neurovascular health in cognitively normal older adults in US POINTER
Authors: Brinkley Tina E , Garcia Katelyn R , Mitchell Gary F , Tegeler Charles H , Sarwal Aarti , Bennett John , Kitzman Dalane W. , Lockhart Samuel N. , Leng Xiaoyan , Baker Laura D , Snyder Heather M , Harrison Theresa M. , Landau Susan M. , Bailey Margie J , Shaltout Hossam A 
Published: January 2025

AbstractBackgroundObesity is associated with adverse changes in the structure and function of both the brain and the vasculature and may modify risk for Alzheimer’s disease (AD). However, the degree to which excess total and central adiposity contribute to overall disease burden in late‐life is unclear. We investigated baseline associations between obesity, AD‐related pathology, and neurovascular health in 255 participants enrolled in the U.S. POINTER trial (mean age: 68.2±5.4 years, 53% female, 29% people of color).MethodBaseline assessments included anthropometry to determine body mass index (BMI) and waist circumference and neuroimaging (MRI and PET) to assess global amyloid burden, entorhinal and temporal metaROI tau burden, hippocampal volume, cortical thickness, and white matter hyperintensity volume (WMHV). Ultrasound, tonometry, and continuous heart rate and blood pressure monitoring were also performed to evaluate the aorta and carotid arteries and assess autonomic function. Linear regression was used to examine cross‐sectional associations between the outcomes of interest adjusting for age, sex, race/ethnicity, education, and site.ResultThe majority of participants were overweight or obese (n = 220, 86.3%, mean BMI: 30.5±5.6 kg/m2) or had abdominal obesity (n = 190, 74.5%, mean waist circumference: 104.4±14.4 cm2). Overweight and obese individuals were more likely to be Black or Hispanic (p = 0.0028), have less than a college degree (p = 0.0245), and have altered carotid artery properties, including lower characteristic impedance (p = 0.0117), higher pulsatility (p≤0.01), and a larger diameter (p<0.01). Both BMI and waist circumference were positively associated with carotid pulsatility, carotid transmission coefficient, carotid diameter, and aortic normalized impedance, whereas negative associations were found with aortic pulsatility and aorto‐carotid reflection coefficient (all p<0.02). BMI was also positively associated with hippocampal volume (p<0.01). In addition, several neurovascular outcomes were associated with AD‐related pathology, independent of obesity. Notably, higher carotid‐femoral pulse wave velocity, lower baroreflex sensitivity, and lower heart rate variability were associated with greater WMHV (p≤0.01), while higher aortic pulsatility was associated with greater entorhinal and metaROI tau (p = 0.0132).ConclusionIn older adults at risk for AD, overweight/obesity is associated with altered aortic and carotid structure and function, which likely has important downstream effects on the brain and may impact the development of AD.
Sex/Gender Differences in the Cognitive‐Aging Effects of Head Injuries due to Interpersonal Violence
Authors: Hanes Douglas William 
Published: January 2025

AbstractBackgroundTraumatic brain injury is a risk factor for worse later‐life brain health, including dementia. Yet the role of interpersonal violence and its gendered nature in the TBI–cognition relationship has yet to be fully studied. While men and women alike commit and experience violence, gender‐based violence (GBV)—which primarily targets women, transgender and gender‐nonconforming people, and from which they tend to suffer worse injuries than men—is understudied. Using population‐based survey data, we examine gender differences in cognitive effects of self‐reported head injuries due to interpersonal violence.MethodWe use data from the Health and Retirement Study (HRS; n = ), a survey of Americans age 51+. It gathered self‐reported lifetime head‐injury data in 2014, allowing participants to specify injury causes; we restricted our analysis to participants injured in a physical altercation or shot in the head. Participants also indicated injury severity in several binary variables. We calculated summary statistics to compare injury prevalence between men and women. To assess cognitive effects, we used multilevel regressions with subsequent cognitive performance (27 points possible) as the outcome variable and interaction between injury severity and sex/gender as the primary predictor variable, adjusting for race/ethnicity, education, and wealth.ResultWhile men were likelier to report head injuries due to fights (c2 = 12.884; p < 0.001), women were over twice as likely to report ongoing health problems due to head injury (c2 = 10.638; p = 0.001), likelier to have been hospitalized due to a fight or gunshot‐caused head injury (c2 = 5.533; p = 0.019), and nearly 5x likelier to report losing consciousness due to choking (c2 = 5.069; p = 0.024). Women hospitalized due to a fight or gunshot experienced worse cognitive effects (b = ‐2.428; p = 0.004) than hospitalized men relative to unhospitalized men (b = ‐2.600, p = 0.005 and b = ‐3.372, p < 0.001, respectively).ConclusionIn keeping with existing literature, women suffer worse injuries than men from interpersonal violence; women also have worse cognitive harms due to head injuries than do men. The reasons for these outcomes, and their relationship to GBV, requires further investigation.
Integrating NACC UDS with RDW EHR data for MCI prediction and identification of MCI related features
Authors: Wang Gefei , Xu Baijia , Xu Wanwan , Dodge Hiroko H , Zhao Yize 
Published: January 2025

AbstractBackgroundMild Cognitive Impairment (MCI) is considered as a transitional state between age‐related cognitive decline and dementia. Accurate prediction of those at risk of MCI is important for timely intervention and treatment of Alzheimer’s disease. In this study, we show that incorporating the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) with rich resources from Electronic Health Records (EHR), including comorbidities and medication histories, can achieve higher prediction accuracy, compared to using only one resource.MethodIn this study, we used the Research Data Warehouse (RDW) EHR data from Oregon Health & Science University (OHSU) as auxiliary information. We first cleaned variables by rescaling and one‐hot encoding. Missing data were imputed by the average of observations. Only data recorded before MCI transition were included. To fairly compare different feature sets, the same random forest classification model with 100 estimators is used. Feature importance from the random forest identified key factors.Result143 patients with both NACC records and OHSU RDW EHR were used after data cleaning. Among them, 85 patients transitioned to MCI. 100 random splits of training and testing datasets were generated to assess the accuracy. An Area Under the Curve (AUC) 0.671±0.075 (mean±std), sensitivity 0.759±0.102 and specificity 0.477±0.107 were achieved using variables from both NACC UDS and OHSU RDW EHR. The AUC is significantly higher than the AUC obtained only using NACC UDS (0.629±0.071) or OHSU RDW EHR(0.556±0.089), with p‐values < 0.001 using the Wilcoxon singed‐rank test (Fig. 1). The sensitivity and specificity obtained only using NACC UDS (0.726±0.108/0.457±0.109) or OHSU RDW EHR(0.687±0.126/0.333±0.140) are also relatively low. Feature importance suggested that some factors may have higher impact on MCI progression (Fig. 2). Green and orange features are from NACC UDS and OSHU RDW EHR, respectively.ConclusionOur exploration on combining clinical variables in NACC USD with OHSU RDW EHR shows promising ability for early prediction of MCI risk. In addition to NACC UDS, hospital diagnosis histories, especially for diseases like other mental disorders, sleep disorders, pain and hypotension, provide useful information. Our study shows the potential of integrating data resources for improved prediction of MCI and identification of related factors.
Social determinants in early midlife and trajectories in cognition and brain integrity in midlife
Authors: Dintica Christina S. , Cheunkarndee Julia , Bryan R. Nick , Launer Lenore J. , Yaffe Kristine 
Published: January 2025

AbstractBackgroundSocial determinants of health (SDOH) are increasingly recognized as important drivers of inequities in cognitive outcomes. However, most existing evidence is based on individual SDOH components. We evaluated the relationship between a cumulative SDOH index in early midlife and change in cognition and brain volume.MethodsWe included 3,224 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with information on SDOH in early midlife (mean age 40.0 ± SD 3.6) and cognitive assessments and brain MRI 10, 15, and 20 years later. A weighted SDOH score representing the cumulative number of unfavorable SDOHs, identified from 13 components across 4 domains (economic stability, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 1 being the least favorable). Cognition was assessed using the Digit Symbol Substitution Test (DSST), the Stroop Test, and the Rey Auditory Verbal Learning Test (RAVLT). 1,108 participants had MRIs measuring white matter hyperintesities (WMHs) and total gray matter (GM). Mixed linear regression was used to examine the association between the SDOH index quartiles and cognitive and MRI outcomes adjusting for age, sex, race, and intracranial volume (for MRI).ResultsParticipants in the least favorable SDOH quartile had steeper decline in the Stroop test (b: ‐0.16, 95% CI: ‐0.31 to ‐0.02) and the RAVLT (b: ‐0.04, ‐0.08 to ‐0.01), but not the DSST (b: ‐0.08, ‐0.21 to 0.07), compared to the most favorable SDOH quartile (Figure 1, A‐C). Moreover, participants in the least favorable SDOH quartile had higher accumulation of WMHs over time (b: 196.31, 95% CI: 89.41 to 303.21) and a steeper decline in total GM (b: ‐565.10, 95% CI: ‐1021.52 to ‐108.69), compared to quartile 4 (Figure 1, D, E). Quartiles 2 and 3 were not significantly different in rates of change in any of the cognitive tests or MRI measures compared to quartile 4.ConclusionHigh social disadvantage in early midlife is associated with accelerated decline in cognition and worsening of brain integrity already at midlife. Further studies identifying underlying mechanisms linking SDOH with cognition are needed to establish prevention strategies.
Characterizing White Matter Hyperintensity (WMH) Patterns with Texture‐Based Analysis
Authors: Alshikho Mohamad J. , Morales Clarissa , Pyne Jeffrey D. , Amarante Erica , Lao Patrick J. , Turney Indira C. , Edwards Natalie C. , Gu Yian , Manly Jennifer J. , Mayeux Richard , Brickman Adam M. 
Published: January 2025

AbstractBackgroundWhite matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted MRI scans. They vary in size, location, and intensity, suggesting different underlying conditions like small vessel disease and inflammation. This variation potentially links WMH to outcomes ranging from normal aging to severe neurological disorders. We used a texture analytic approach, Gray‐Level Co‐occurrence Matrix (GLCM), to characterize the intensity heterogeneity of WMHs. This method classifies WMHs into distinct zones based on homogeneity scores that represent uniformity in signal intensity. We explored associations among white matter microstructure, cerebral blood flow, and WMH volume within these zones.MethodOne hundred sixty‐one participants from the Washington Heights‐Inwood Columbia Aging Project (WHICAP) were included. White matter hyperintensities were labeled using in‐house software, which also created normalized homogeneity maps through GLCM. These maps were used to define three WMH zones based on their degree of homogeneity (i.e., homogeneous, intermediate, and heterogeneous) (Figure 1). We examined the relationship among fractional anisotropy (FA), cerebral blood flow (CBF), and WMH volume within these WMH zones and compared CBF and FA values across the zones.ResultIn homogeneous and intermediate WMH zones, there was no association between FA and CBF (rhomo.=0.022, phomo.=0.787; rinter.=‐0.12, pinter.=0.132). However, both FA and CBF negatively correlated with WMH volume in these zones (rFA‐homo.=‐0.348, pFA‐homo.< 0.0001; rFA‐inter.=‐0.538, pFA‐inter.< 0.0001; rCBF‐homo.=‐0.36, pCBF‐homo.< 0.0001; rCBF‐inter.=‐0.40, pCBF‐inter.< 0.0001).In the heterogeneous zone (Figure 2), FA and CBF were negatively correlated (rhetero.=‐0.422, phetero.< 0.0001). CBF, but not FA, was associated with WMH volume (rCBF‐hetero.=‐0.471, pCBF‐hetero.< 0.0001; rFA‐hetero.=0.085, pFA‐hetero.=0.300)In homogenous WMH regions, both [FARatio (0.776±0.009) and CBFRatio (0.96±0.014)] values were lower than in intermediate [FARatio (0.84±0.009) and CBFRatio (0.97±0.014)] and heterogeneous zones [FARatio: (1.029±0.009), CBFRatio: (1.002±0.014)].(Figure 3)ConclusionDistinct correlation patterns exist between CBF and FA in WMH clusters defined by intensity heterogeneity. Homogeneous zones, likely reflect older lesions, show low microstructural integrity and minimal relationship with CBF, suggesting high gliosis. Heterogeneous zones, possibly reflecting recent white matter damage, show associations between CBF and microstructure, potentially indicating active inflammatory processes contributing to vascular injury.