bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating Life Simple Seven’s Influence on Brain Health Outcomes: The Intersection of Lifestyle and Dementia
Authors: Denier‐Fields Diandra N. , Gagnon Ronald E. , Ryther Brenda , Canovi Ian A. , Wilkinson Diane , Sparks Lia J. , Rivera‐Rivera Leonardo A. , Betthauser Tobey J. , Bendlin Barbara B. , Johnson Sterling C. , Engelman Corinne D. 
Published: January 2025

AbstractBackgroundLifestyle factors have been studied for their role in dementia, but few have comprehensively assessed both Alzheimer’s disease (AD) and cerebrovascular disease (CBVD) pathologies. This study innovatively integrates AD, CBVD, and cognitive composite scores (CCS) within the same cohort to investigate the association of the Life Simple Seven (LS7) score with a broad spectrum of dementia‐related outcomes. Our research aims to unravel the intricate relationships between lifestyle and various dementia pathologies, challenging conventional research paradigms.MethodAnalyzing 1210 Wisconsin Registry for Alzheimer’s Prevention (WRAP) study participants, we focused on LS7 score calculations from questionnaire data and clinical vitals (Table 1). We assessed brain health indicators over intervals of 2‐4, 4‐6, and 6‐8 years post‐LS7 scoring. CBVD outcomes included white matter hyperintensities (WMH) and cerebral blood flow (CBF); CCS outcomes comprised delayed recall, executive function, immediate learning, and the Pre‐Clinical Alzheimer Cognitive Composite 3 (PACC3); AD outcomes involved PET amyloid (PiB) and tau (MK6240) imaging (Table 2). Our study controlled for age, sex, race/ethnicity, apolipoprotein E ε4 (APOE ε4) count, years of education, and practice effects as appropriate for each outcome.ResultHigher LS7 scores were associated with 0.06 lower %WMH at 2‐4 years, per point increase in LS7 score (n = 275, p = 0.005), contrasted with 0.05 higher %WMH annually for participants over 65 (p<0.001; Figure 1). In relation to CBF, although there is a general decrease during aging that accelerates in disease states, higher LS7 scores were associated with relatively higher ASL perfusion in both gray and white matter at 2‐4 and 6‐8 years. For PACC3 scores, one point increase in LS7 score was associated with 0.04 higher scores (n = 872, p = 0.041) at the 2‐4 year interval, while an increase in age was associated with lower PACC3 scores by 0.05 (p≤0.001). No significant associations were found between LS7 scores and the remaining CCS or AD imaging.ConclusionThis study highlights the impact of cardiovascular health, influenced by lifestyle choices, on cognition, likely through the cerebrovascular pathway. It underscores the importance of lifestyle interventions in vascular dementia prevention and management, offering critical insights for developing strategies to mitigate cognitive decline and dementia risk.
Correlates of missed or late versus timely diagnosis of dementia in healthcare settings
Authors: Chen Yi , Power Melinda , Grodstein Francine , Capuano Ana W. , Lange‐Maia Brittney S , Moghtaderi Ali , Stapp Emma K , Bhattacharyya Joya , Shah Raj C. , Barnes Lisa L. , Bennett David A. , James Bryan D 
Published: January 2025

AbstractBackgroundPrevious research suggests dementia is undetected in healthcare settings for more than half of those with dementia. Most research on underdiagnosis of dementia has focused on the presence or absence of a clinical diagnosis in claims or the medical record without addressing differences in the timeliness of a diagnosis. Little is known about factors that may be related to the timeliness of clinical dementia diagnosis.MethodIn five longitudinal cohorts at Rush Alzheimer’s Disease Center, we identified participants with incident dementia based on annual research assessments from 1994 to 2019 and examined the timing of dementia diagnoses in Medicare claims. Receiving a claims diagnosis within three years prior to or one year following incident dementia was considered a “timely diagnosis”; the remaining were categorized as “underdiagnosis”, including late or missed diagnosis. We assessed correlates of timely versus under‐ diagnosis, including sociodemographic characteristics, health, and psychosocial factors, using bivariate analyses and adjusted logistic regressions.ResultOf the 710 participants with incident dementia, 54% (n = 385) received a timely diagnosis. In logistic regressions adjusting for demographic characteristics, we found Black older adults had twice the odds of underdiagnosis versus timely diagnosis (OR = 2.15, 95% CI: 1.21‐3.82). Higher mid‐life income (on 10‐level scale) was related to 11% lower odds of underdiagnosis (OR = 0.89, 95% CI: 0.81‐0.97). Better cognitive function (OR = 1.48, 95% CI: 1.10‐1.98 for one standard‐deviation higher cognitive function), and fewer comorbidities (OR = 0.94, 95% CI: 0.89‐0.98 for one‐unit increase in Elixhauser Comorbidity Index) at the time of dementia onset were associated with diagnostic delay. The number of encounters with the healthcare system, disability, frailty, social network, psychosocial factors, and APOE‐4 genotype were not associated with diagnostic timing.ConclusionWhen considering the timeliness of dementia diagnosis, two socio‐demographic characteristics (Black race and lower income) and two health characteristics (better cognitive function and fewer comorbidities) were related to receiving a late/missed diagnosis. Observed correlates of timeliness may have implications for improving dementia diagnosis and care.
T1/T2 weighted ratio mapping to assess intracortical myelination in autosomal dominant Alzheimer's disease
Authors: Sgalia Alessia , Ocal Dilek , Veale Thomas , Ferguson Damien , O'Connor Antoinette , Malone Ian B. , Cash David M , Fox Nick C , Weston Philip SJ 
Published: January 2025

AbstractBackgroundIdentifying early pathological changes in Alzheimer’s Disease (AD), and accounting for variability in progression between individuals, is crucial for timely and effective intervention. While Amyloid‐b, tau, and neuronal loss are core pathological processes in AD with established biomarkers, myelin alterations have been shown to occur but remain under‐investigated. The T1/T2w ratio represents an accessible MRI‐based marker, providing a potential proxy measure of myelin integrity. Autosomal dominant AD (ADAD) provides a unique opportunity to investigate AD‐related changes across its continuum, estimating time to/from symptom onset from family history. This study examines the T1/T2‐weighted ratio as an indicator of extra‐neuronal AD pathology in ADAD.MethodSeventy‐two ADAD family members were included: 28 presymptomatic mutation carriers, 20 symptomatic mutation carriers and 24 non‐carrier controls (Table 1). Volumetric T1 and T2‐weighted MRI sequences were acquired. Whole brain preprocessing and T1/T2w ratio were calculated for each participant using MRtool in SPM12 (bias correction, rigid registration, calibration, ratio), followed by tissue segmentation, DARTEL, normalisation and smoothing. Voxel‐wise analysis compared T1/T2 across 1) presymptomatic mutation carriers vs. non‐carriers and 2) symptomatic mutation carriers vs. non‐carriers, adjusting for age and sex. In mutation carriers only, we assessed correlations between T1w/T2w ratio and 1) estimated years to/from onset (EYO), and 2) Mini‐Mental State Examination (MMSE) scores.ResultSymptomatic ADAD mutation carriers had lower T1w/T2w ratios than non‐carriers in the medial parietal lobe (t = 7.06, p <0.001 family‐wise error (FWE) corrected) (Figure 1), likely reflecting altered myelin integrity. After FWE correction, no significant differences were observed between presymptomatic mutation carriers and non‐carriers. Across all mutation carriers, there was a positive correlation between T1w/T2w and EYO (i.e. lower T1/T2 was associated with less time to symptom onset), with significant clusters in the praecuneus (p < 0.05 FWE‐corrected) (Figure 2). There was a positive correlation between T1w/T2w and MMSE (t= 5.82, p <0.05 FWE‐corrected) (Figure 3).ConclusionT1w/T2w ratio is reduced in ADAD, suggesting reduced myelin integrity, and is associated with measures of disease stage (EYO) and severity (MMSE). T1w/T2w ratio could therefore provide a feasible biomarker of myelin integrity, potentially enhancing early AD prognostication, monitoring and treatment development.
Childhood attention‐deficit hyperactivity disorder (ADHD) and cognitive function in later life: Analysis of HRS data
Authors: Stinchcombe Arne , Hanes Douglas William 
Published: January 2025

AbstractBackgroundAttention‐deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition marked by cognitive deficits (e.g., challenges sustaining attention, distractibility). Symptoms of ADHD typically manifest in childhood and can interfere with engagement in school activities, chores, and interpersonal relationships. In many cases, symptoms endure into adulthood and older adulthood. ADHD in adulthood and mild cognitive impairment (MCI) share many overlapping cognitive (e.g., impaired executive functions) and non‐cognitive (e.g., depression, poor sleep) symptoms, complicating differential diagnosis. Currently, the association between ADHD and cognitive impairment associated with aging, such as MCI, remains unclear. The purpose of this present study was to examine differences in cognitive function by ADHD status in an aging sample.MethodData were drawn from the Health and Retirement Study, a longitudinal survey of U.S. residents aged ≥51 years. Waves 4‐14 (1998‐2018) were used in the present analysis. Of the 10,804 participants included for analysis, 99 participants (i.e., 0.9% of the sample) reported having an ADHD diagnosis in childhood. Cognitive function was measured on a 27‐point scale. The primary analysis consisted of a series of multiple linear regression models, treating cognition as the outcome, and adjusting for age, sex/gender, wealth, education, and race.ResultDescriptive analysis showed that participants with ADHD reported lower levels of education and were more likely to have experienced homelessness and depression. Participants with ADHD showed lower cognitive scores at baseline (m = 14.52) compared to non‐ADHD peers (m = 17.01, t = 5.90, p<.001). Multivariable analysis revealed that after adjusting for covariates, ADHD status was associated with lower cognitive scores in the study (B = ‐1.88, p<.001). ADHD participants showed a similar slope of decline to non‐ADHD peers over time; however, cognitive scores were consistently lower at each time point for ADHD participants.ConclusionIndividuals with self‐reported childhood ADHD diagnoses demonstrated lower cognitive scores compared to their non‐ADHD counterparts, suggesting a persistent impact of ADHD on cognitive function in later life and potential risk for cognitive impairment. These findings emphasize the need for further research to elucidate the complex relationship between ADHD and cognitive impairment and underscore the importance of considering ADHD in the broader context of cognitive health throughout the lifespan.
Cognitive and Brain Structure Correlates of Plasma Biomarkers in Traumatic Encephalopathy Syndrome
Authors: Emanuel Olivia M , Matusz Emily F , Lee Shannon Y. , Bove Jessica , Smith Karen , Kramer Joel H. , Rabinovici Gil D. , Asken Breton M. 
Published: January 2025

AbstractBackgroundTraumatic encephalopathy syndrome (TES) is a proposed framework for the clinical syndrome resulting from chronic traumatic encephalopathy and other neurodegenerative effects of repetitive head impacts (RHI). TES symptoms can mirror Alzheimer's disease (AD) despite absence of hallmark AD pathology. We investigated whether GFAP, NfL, and IL‐6 correlated with cognition and brain volume changes within TES relative to AD.MethodWe studied 96 participants from the UCSF Memory and Aging Center (N=35 RHI/TES; 24 of whom were AD biomarker‐negative, TESAD‐; N=61 biomarker‐confirmed AD phenotype, no RHI; Table 1). Plasma was analyzed for GFAP, NfL, and IL‐6 (age‐ and sex‐adjusted). Cognitive measures included composite memory and executive functioning scores (demographically‐adjusted). MRI was obtained concurrent to blood draws and several regions of interest were analyzed (demographic‐ and total intracranial volume‐adjusted): frontal, temporal, parietal, occipital, hippocampus, subcortical. Spearman’s rho assessed associations between plasma biomarkers, cognition, and brain volume. A priori alpha was p<.05, but associations with at least medium effect size (rho ≥0.3) were interpreted as potentially meaningful given small N in TES and TESAD‐ subgroups.ResultIn TES, higher GFAP was associated with lower hippocampal volume (rho=‐0.33, p=.09) and worse memory (rho=‐0.44, p=.02). Results were similar in TESAD‐ subgroup (GFAP‐hippocampus: rho=‐0.45, p=.07; GFAP‐memory: rho=‐0.42, p=.07). IL‐6 appeared most related to brain volume in the TESAD‐ subgroup, where higher IL‐6 correlated with lower volumes in all regions (rho’s ‐.43 ‐ ‐.63, p’s=.004 ‐ .06), but not with cognition. In AD, both higher NfL and GFAP were associated with lower brain volume in several regions and with worse cognition but, notably, neither related to hippocampal volume (NfL: rho=‐.11, p=.47; GFAP: rho=.02, p=.91). IL‐6 did not relate to brain volume or cognition in AD (Figure 1).ConclusionPlasma biomarkers reflect different regions of atrophy and cognitive change in TES vs. AD. Inflammation (IL‐6) may play a distinctive role in the pathophysiology underlying atrophy in TES. While recent work highlights astroglial activation (GFAP) is a putative AD‐related biomarker, it may uniquely relate to hippocampal changes in TES. Ongoing work is needed to unravel the clinical utility of plasma biomarkers for characterizing the neurodegenerative effects of RHI and underlying TES symptoms.
Comparison of dementia incidence and risk factor associations in All of Us against the nationally representative Health and Retirement Study
Authors: Wang Jingxuan , Chen Ruijia , Hayes‐Larson Eleanor , Mayeda Elizabeth Rose , Choi Minhyuk , Ackley Sarah F , Glymour M. Maria 
Published: January 2025

AbstractBackgroundThe All of Us (AoU) Research Program, an ongoing large‐scale research initiative enrolling diverse groups across the U.S offers a valuable opportunity for dementia research. It is vital to assess if AoU findings are applicable to the general population. We compared dementia incidence and risk factor associations in AoU to those in a population‐based cohort, the Health and Retirement Study (HRS).MethodAoU participants aged ≥ 60 without a dementia diagnosis at baseline (N = 130,551, mean age = 69.6) were included. We identified all‐cause dementia cases by ICD codes from linked EHRs. We included HRS participants aged ≥ 70 from 2000 to 2016 who had no dementia status before baseline (N = 14,016, mean age = 73.4). Dementia status was determined at each wave using a validated algorithm (Expert Model). We calculated age‐specific dementia incidence rates overall and by sex and race/ethnicity. We used Cox models to evaluate associations of education, obesity (body mass index ≥ 30), smoking history (ever vs not), and type 2 diabetes (T2D) with incident dementia, adjusting for age, sex, and race/ethnicity.Result1,403 dementia cases accrued during a mean of 2.6 years follow‐up in AoU compared to 4,814 dementia cases during a median of 7.1 years follow‐up in HRS (Table 1). Age‐specific dementia incidence rates over 70 years were lower in AoU compared with HRS, with more pronounced differences at older ages (Figure 1). Risk factor associations showed larger relative effect sizes in AoU, except for education, which showed similar associations (Figure 2). For example, the hazard ratio for T2D and dementia in AoU (HR = 2.89, 95%CI = 2.59‐3.23) was larger than in HRS (HR = 1.69, 95%CI = 1.57‐1.82, Figure 2).ConclusionDementia incidence rates were much lower in AoU than HRS, consistent with prior work showing a healthy volunteer bias for study enrollment. This may also represent underdiagnosis of dementia in the EHR or overdiagnosis in HRS. Associations between risk factors and dementia were similar or stronger in AoU compared to the HRS. Future studies should approach the generalization of AoU study findings to the US adult population with caution.
Does the message matter: A strategy to improve retention in recruitment registries
Authors: Lee Yongjun , Grill Joshua D , Gillen Daniel L , Witbracht Megan G. , Hoang Dan , Delehoy Brandon 
Published: January 2025

AbstractBackgroundTo be successful, recruitment registries must retain participants until they can be recruited to studies. Yet, strategies and tactics to improve retention in online recruitment registries remain understudied. This study seeks to quantify the preferences of registry participants’ when it comes to video message content aimed at increasing registry renewal.MethodActive participants of the UC Irvine Consent‐2‐Contact (C2C) Registry were invited to participate in a discrete choice experiment to test whether four short video messages about the reasons to renew, delivered alone or in combination, would elicit a clear preference. The messages highlighted reasons that individuals might choose to renew their enrollment in the registry: 1) some recruiting studies offer financial compensation, 2) to advance research toward improved outcomes in health and disease, 3) to be matched to a study relevant to one’s own health, and 4) promotion of novel research within the registry using data collected at renewal. From 15 possible combinations, participants viewed 7 random pairs of videos. After viewing each pair, participants were asked to select the video that would most compel them and others to renew their participation in the registry. Each participant was asked to complete a final survey including 8 Likert scale items assessing participant attitudes toward renewal. The study employed a Bradley‐Terry model to identify the combination deemed favored by the participants. To estimate topic‐specific preferences, interaction between the topics across all combinations, along with covariate adjustments for participant demographics were modeled via an extension of the Bradley‐Terry model in combination with the study’s fractional factorial design.ResultStatistical power to identify the most preferred topic along with topic‐specific orderings were carried out via simulation. Data collection is underway. Presented results will include efficacy of individual messages as well as optimal message combinations and concordance with survey results.ConclusionThis study introduces a novel design where the effect of video messages from a fractional factorial combination of four incentives can be estimated through a paired rank analysis model. Results will inform a future randomized factorial design trial of retention interventions.
GEAR 2.0 ‐ Care Transitions
Authors: Shah Manish N 
Published: January 2025

AbstractOlder adults use the emergency department (ED) as an important source of acute illness care, making over 20 million visits annually. Persons living with dementia are twice as likely to use the ED and 1.5 times more likely to have an avoidable visit. When in the ED, they may not be able to give the clinicians a complete and accurate medical history, including information regarding their dementia. Further, they struggle with the environment and conditions. These challenges, along with other risks, put patients living with dementia at greater likelihood for poor outcomes.Approximately 50 percent of patients with impaired cognition are discharged to their homes after receiving ED care, but approximately 40 percent of those discharged home will experience an adverse event (ED revisits, other hospitalizations, or death) in the 30 days following discharge—a rate significantly higher than for those without impaired cognition.This session will review the interventions delivered to patients with impaired cognition to improve ED discharge transitions and the measures of quality ED discharge transitions that are important to ED patients with impaired cognition and their care partners.
ED‐to‐community care transitions for persons living with dementia
Authors: Gettel Cameron 
Published: January 2025

AbstractObjectivesLittle data exists to date regarding effective interventions to improve emergency department (ED)‐to‐community care transitions for persons living with cognitive impairment (PLWCI) and their care partners. We sought to develop, refine, and pilot test the innovative pairing of artificial intelligence (AI)‐enabled digital advisors and an occupational therapist‐led care coach intervention to improve ED‐to‐community care transitions for PLWCI and their care partners.MethodsWe used a mixed methods, multi‐phased approach to develop the intervention, with PLWCI and care partners sampled from the LiveWell Dementia Specialists network. In the first phase, we conducted semi‐structured focus groups and two researchers coded the professionally transcribed data using a combined deductive and inductive approach. In the second phase, we performed a 2‐day design thinking workshop using a user‐centered design approach, involving PLWCI, care partners, health care professionals, community‐based partner organizations, technologists, and AI experts. In the final phase, we pilot tested the paired intervention among PLWCI and care partners experiencing ED‐to‐community care transitions, assessing: 1) intervention outcomes and 2) patient‐ and care partner‐centered outcomes.ResultsIn the first phase, we performed two focus groups, involving a total of 16 participants, with PLWCI and care partners expressing: 1) concerns that their unique needs related to cognition were not addressed in the ED setting, 2) frustration with the ED discharge process and their perceived ability to follow‐up in the outpatient setting and obtain desired resources, and 3) openness to the incorporation of AI to facilitate successful ED‐to‐community care transitions. In the second phase, 23 individuals participated in the design thinking workshop. We characterized perceived barriers and facilitators for intervention adoption during open forum discussions and identified 10 Lessons Learned for future investigators to consider in intervention development. In the third phase, 16 participants have completed all surveys up to 30‐day follow‐up with evidence of improvements in the 4‐item Zarit Caregiver Burden scale (13.9 to 12.2) and the Fortinsky Caregiver Self‐Efficacy Scale (52.9 to 64.8).ConclusionPLWCI and care partners were integrally engaged in the co‐creation of a two‐component novel intervention to improve ED‐to‐community care transitions.