bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex Differences in Comorbidity Patterns and the Associations with Risk of Alzheimer’s Disease and AD‐Related Dementias among Adults Aged 65 and Older: Findings from the United States Medicare Current Beneficiaries Surveys, 2018‐2020
Authors: Liu Longjian , Gracely Edward J , May Nathalie S , DiMaria‐Ghalili Rose Ann Rose Ann , Eisen Howard J 
Published: January 2025

AbstractBackgroundTo provide a nationally representative estimate of the burden of multiple comorbidities (MCM) among community‐dwelling Medicare beneficiaries with Alzheimer’s disease (AD) and AD related dementias (ADRD).MethodWe analyzed national sampling data in Medicare beneficiaries aged ≥65 (n = 34,318) from the 2018‐2020 Medicare Current Beneficiaries Surveys. AD/ADRD and twelve chronic comorbidities (hypercholesterolemia, hypertension, diabetes, coronary heart disease, heart failure, stroke, depression, mental disorder, chronic kidney disease, chronic obstructive pulmonary disease, arthritis, and osteoporosis) were examined. A novel age‐adjusted regression weighted MCM index was developed by taking into account the relative impact of each comorbidity on the risk of AD/ADRD. Logistic regression models estimated adjusted odds ratios (AORs) of commodity and the MCM index for AD/ADRD, adjusting for sociodemographic, body mass index and behavior factors.ResultA total of 1,802 AD/ADRD cases (5.3%) were identified, representing an estimated 5,580,421 AD/ADRD cases in the nation’s Medicare beneficiaries. In the 65‐74 age group, the prevalence of AD/ADRD was 1.8% in males and 1.4% in female (p = 0.11), while in those aged ≥75, it was 6.1% in males and 7.6% in females (p = 0.001). AD/ADRD individuals more often had ≥4 comorbidities than those without AD/ADRD (52.6% vs. 30.9% in males, and 58.3% vs. 34.8% in females). In males, of the 12 comorbidities, depression exhibited the highest AOR (95%CI) at 4.62 (3.70‐5.78) for AD/ADRD risk, followed by mental disorder at 4.36 (2.88‐6.59), and stroke at 3.19 (2.51‐4.06). The same disorders were the top three in females, but in a different order, namely mental disorders at 4.79 (3.44‐6.68), stroke at 3.50 (2.79‐4.39), and depression at 2.92 (2.41‐3.54). An increase in MCM index score was associated with 2.13 (1.92‐2.37) higher AD/ADRD risk in males, and 1.65 (1.52‐1.80) higher risk in females.ConclusionThe study highlights that AD/ADRD poses a substantial public health burden in the nation, with older females experiencing a significantly higher prevalence of AD/ADRD. The association of sex and specific comorbidity profiles on AD/ADRD risk is evident, emphasizing the need for further studies of the disease mechanisms and the potentially targeted prevention strategies by addressing these factors.
Health Coaching Intervention Retained ANU‐ADRI Scores Over a 2‐year period in APOE e4 Carriers Among Older Adults at Risk for Alzheimer’s Disease
Authors: Gray Michelle , Campitelli Anthony , Urbina Ray G , Jones Megan 
Published: January 2025

AbstractBackgroundThe Apolipoprotein epsilon 4 allele (APOE ε4) gene is known as the most prevalent genetic risk factor for Alzheimer’s disease (AD). However, many lifestyle risk factors that are modifiable influence the development of AD. Reducing the prevalence of risk factors can prevent or delay up to 33% of AD cases. Health coaching is known to improve health over time in older adults by using a motivational interviewing technique resulting in positive behavior modification. The purpose of this study was to determine if a 2‐year health coaching intervention improves AD risk score among older adults at risk for AD aged 60 and 75 years of age.MethodAdults between the ages of 60‐75 (n = 106) were randomly assigned to a health coaching (HC) or health education (HE) control group. HC met with a health coach once every 4‐6 weeks and HE received biweekly educational emails addressing AD risk factors. Each participant tested at 4 time points: 0 (baseline), 4, 12, and 24 months. At baseline the participants had blood drawn to test for APOE ε4 (carrier and non‐carrier). At each time point the participants completed the Australian National University‐Alzheimer’s Disease Risk Index (ANU‐ADRI), a validated tool to predict AD. To determine significant differences between time points for each group and apoe ε4 carrier status a mixed factorial ANOVA (α = .05) was used.ResultAmong both carrier groups the HE and HC interventions had no significant mean difference between baseline and 24 months (Non‐carriers HE p = .936, HC p = .123; Carriers HE p = .109, HC p = .832). No meaningful difference between non‐carrier HE (‐.881) and HC (‐1.513) or Carrier HC (‐0.333) interventions. Overall, HE risk scores increased over time.ConclusionHC intervention retained risk scores among APOE ε4 carriers over 2 years among older adults. Within carrier group, HE risk scores had a meaningful change leading to an increased risk of AD. Though HC did not result in an improvement in AD risk, there was not a decline, as we expected. Health coaching has been shown to have a positive effect on AD risk reduction.
Objective sleep characteristics and cognitive performances: the role of race/ethnicity
Authors: Cavaillès Clémence , Leng Yue , Stone Katie L , Peltz Carrie B. , Yaffe Kristine 
Published: January 2025

AbstractBackgroundA growing body of literature suggests that poor sleep has a negative effect on cognition. However, most prior research has predominantly used subjective sleep data and focused on non‐Hispanic White (NHW) populations. Our goal was to explore the associations between objective sleep characteristics and cognition in a racially/ethnically diverse cohort.MethodWe studied 855 participants from the Health and Aging Brain Study‐Health Disparities (HABS‐HD)‐Dormir study. Objective sleep characteristics, including nighttime sleep duration, wake after sleep onset (WASO), sleep efficiency, and sleep fragmentation index, were assessed by 7‐day wrist actigraphy. Using a battery of cognitive tests, we created four cognitive composite z‐scores for executive function, attention, language, and memory. We used multivariable linear regressions to examine the associations between sleep characteristics and cognitive function, adjusting for age, race/ethnicity, sex, education, marital and cognitive status. Stratified analyses based on race/ethnicity were performed in the presence of interaction.ResultWe studied 370 (43.3%) NHW, 292 (34.2%) Mexican American (MA), and 193 (22.6%) Black participants, with an average age of 66.7 (±8.4) years, and 65.1% female. Compared to NHW participants, both MA and Black participants had shorter sleep duration (7.5, 7.2, and 7.1 hours, respectively, p<0.0001), higher WASO (44.5, 57.0, 61.0 min, p<0.0001), lower sleep efficiency (91.0, 88.0, and 87.0%, p<0.0001), and higher sleep fragmentation index (24.0, 27.2, and 31.9, p<0.0001). Across the sample, longer sleep duration (per 1 hour; β = ‐0.048; p = 0.01) and higher WASO (per 30 min; β = ‐0.041; p = 0.06) were associated with worse executive function. Better sleep efficiency (per 5%; β = 0.080; p = 0.02) was associated with better executive function whereas higher sleep fragmentation index (per 10%; β = ‐0.074; p = 0.06) was associated with worse executive function in Black participants (p interaction = 0.07 and 0.008, respectively). Moreover, higher WASO (per 30 min; β = 0.075; p = 0.04) and higher sleep fragmentation index (per 10%; β = 0.072; p = 0.05) were associated with better attention function in Black participants (p interaction = 0.07 and 0.06, respectively).ConclusionThese findings indicate associations between poor sleep and both executive function and attention; and highlight evidence for racial/ethnic disparities across these relationships.
Subclinical Vascular Risk Composites and Dementia Imaging Biomarkers 17‐20 years later in the Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Rudolph Marc D. , Tanley Jordan E. , Ding Jingzhong , Chen Haiying , Hayden Kathleen M. , Liu Yongmei , Bryan R. Nick , Nasrallah Ilya M. , Dolui Sudipto , Habes Mohamad , Luchsinger José A. , Heckbert Susan R. , Lockhart Samuel N. , Hughes Timothy M. 
Published: January 2025

AbstractBackgroundVascular risk factors captured in midlife represent modifiable features of cardiovascular disease (CVD), stroke, dementia, and dementia‐related neuropathology. Subclinical measures of CVD may help identify specific structural and function aspects underlying vascular contributions to cognitive impairment and dementia over and above conventional dementia risk scores.MethodThe MESA study followed a diverse cohort of 6,814 adults aged 45‐84 years over 6 clinical examinations and annual follow‐up calls since baseline, 2000‐2002. We evaluated relationships between subclinical cardiovascular assessments collected at baseline (Table 1) and neuroimaging biomarkers (Table 2) acquired ∼17‐20 years later in a subset (N = 1420) of older adults free from clinical CVD at baseline with MRI data (Table 2). Factor analyses identified four subclinical composites of arteriosclerosis, atherosclerosis, cardiac function, and blood pressure. Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk (CAIDE) composite scores comprised of age, sex, education, systolic blood pressure, body‐mass index, total cholesterol, physical activity and APOE‐ε4 genotype were calculated. Adjusted general linear models and Random Forest modeling paired 5‐fold 10x‐repeated cross‐validation were used in all analyses.ResultsBaseline subclinical factors were differentially associated with MRI measures at long‐term follow‐up. Subclinical composites of arteriosclerosis and atherosclerosis exhibited the strongest associations with lower global and hippocampal gray matter volume, greater white matter hyperintensity burden, and with higher Aβ‐PET deposition in unadjusted (not shown) and adjusted models (Figure 1, panel A; all p < .05). A composite of cardiac function was modestly associated with MRI measures. Blood pressure was more strongly associated with measures of white matter brain health. Cross‐validated prediction models utilizing individual subclinical measures best predicted measures of global and regional GM volume (Figure 1, panel B). Subclinical measures representing arteriosclerosis (e.g., small artery elasticity, systemic vascular resistance, carotid distensibility) and atherosclerosis (e.g., common carotid intimal‐media thickness, maximum intimal‐media thickness) were most predictive across imaging outcomes assessed. Baseline coronary calcification and carotid distensibility were most strongly associated with MRI measures indexing global GM atrophy (Figure 1, panel C).ConclusionUltimately, our findings may highlight specific subclinical vascular pathways to dementia. Extending this work, we aim to develop trajectory‐based prediction models to better assess vascular aging.
INTERCEPT‐AD: A Gender Analysis of the Phase 1 Experience Among Trial Participants with Early Alzheimer’s Disease and Their Study Partners
Authors: Johnston Kelly , Presnall Carrie , Merikle Elizabeth , Cline Stephanie , Moxon Robyn , Feaster Todd , Siemers Eric 
Published: January 2025

AbstractBackgroundQualitative patient interviews are increasingly conducted alongside clinical trials; interviews administered early in drug development can yield insight into the patient journey. Examination among patient subgroups may identify factors that influence the patient experience, including trial participation. As part of the INTERCEPT‐AD phase 1 study evaluating the safety and tolerability of the Aβ oligomer‐targeting monoclonal antibody ACU193, we conducted semi‐structured qualitative interviews among a subset of participants with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD) and their study partners to obtain feedback on their trial experience and the decision‐making process preceding trial enrollment; results were compared between study participant genders.MethodA subset of study participants and study partners completed qualitative interviews following the final study visit. Topics included referral source, motivations for participating, enrollment decision‐making, concerns regarding study medication and procedures, and positive and negative aspects of participation. Study participant/study partner dyads were defined as female or male according to the gender of the study participant as it was captured in the main study protocol; study partner gender was not obtained. Transcripts were coded and analyzed using principles of qualitative thematic analysis and grounded theory. Differences in concepts mentioned between genders were reported when >20%, and when sample size was sufficient (≥5 dyads reporting a concept with a difference of >2 mentions between genders).ResultTwenty‐eight participants (64.2% female) and their study partners were interviewed, representing 43% of the total randomized trial population (n = 65; 53.8% female). Female dyads accounted for 62% and 70% of those who first heard about INTERCEPT‐AD from social media or physicians, respectively. More female dyads desired additional information about AD (86% of all dyads reporting this concept), to benefit others (75%), and to benefit self (65%) by participating. Regarding the decision to enroll, those who decided independently were exclusively female dyads; female dyads accounted for 71% among those who had pre‐trial concerns about side effects. More female dyads expressed dislike for cognitive tests (83%) and blood draws (78%).ConclusionCertain factors of trial participation differed by participant gender, including motivations for participation and perceived burden of some study procedures.
Conditions prior to age 16 are associated with incident dementia status among older adults in the United States Health and Retirement
Authors: Cockell Scarlet M , Wang Herong , Benke Kelly S , Ware Erin B , Bakulski Kelly M. 
Published: January 2025

AbstractBackgroundDementia is a prevalent neurodegenerative disease with risk attributed to both genetic and environmental factors. Multiple factors contribute to the etiology of dementia, and the relevant exposure window of susceptibility is likely before symptom onset. Conditions and the environment in the early life period have not yet been comprehensively tested for association with later‐life dementia.MethodIn the United States Health and Retirement Study (HRS) (n = 16,509; 2008‐2014 waves) 31 exposures occurring before age 16 were assessed via retrospective questionnaire among those with normal cognition (baseline measure). Incident dementia status (dementia, cognitively impaired non‐dementia, cognitively normal) was assessed over up to ten years of follow‐up. In this exposure‐wide association study, we tested for associations between exposures and cognitive status relative to normal cognition using parallel multivariable logistic models, adjusting sex, age at baseline, follow up time, race/ethnicity, personal education, and parental education.ResultIn the analytic sample, participants were an average of 63 years of age at baseline. Over an average of 10 years of follow‐up, 5.3% of participants had incident dementia and 14.5% cognitive impairment. Depression before age 16 was associated with 1.71 (95% CI: 1.28, 2.26) times higher odds of incident cognitive impairment, relative to those with normal cognition. Headaches or migraines before age 16 were associated with 1.63 (95% CI: 1.18, 2.22) times higher odds of cognitive impairment, relative to normal cognition. Learning problems before age 16 were associated with 1.75 (95% CI:1.05, 2.79) times higher odds of cognitive impairment, relative to normal cognition. Self‐rated health as a child of “fair” (1.856 95% CI: 1.27, 2.64) and “poor” (3.39, 95% CI: 1.91, 5.82) were associated with odds of developing dementia, relative to self‐rated “good” childhood health.ConclusionConditions and exposures originating in early life may be important risk factors for later onset of cognitive impairment or dementia, extending the relevant window of susceptibility. Longitudinal research may be subject to challenges related to recall of information and differential survival and follow‐up studies are needed.
Living alone, medial temporal tau pathology, and loneliness in cognitively normal older adults during the COVID‐19 pandemic
Authors: Zide Benjamin S , Gagliardi Geoffroy Pierre , Jacobs Heidi I.L. , Gatchel Jennifer R. , Quiroz Yakeel T. , Marshall Gad A , Johnson Keith A , Sperling Reisa A , Vannini Patrizia , Donovan Nancy J 
Published: January 2025

AbstractBackgroundSocial restrictions during the COVID‐19 pandemic raised acute concerns about the impacts of loneliness on older adults’ well‐being, particularly for those who live alone. Loneliness is a perceived state of isolation from others that is only partly determined by quantities of social ties and interactions. Drawing a subsample from the Harvard Aging Brain Study, we measured self‐reported loneliness in older adults living alone and those living with others during the pandemic. We leveraged pre‐COVID‐19 loneliness and neuroimaging data to evaluate whether Alzheimer’s disease (AD) pathology contributed to rising loneliness levels in community dwelling older adults living alone during the pandemic.MethodOne‐hundred and six cognitively unimpaired older adults underwent clinical assessments of self‐reported loneliness (UCLA Loneliness scale), cognitive performance (Preclinical Alzheimer’s Cognitive Composite [PACC]), depression (Geriatric Depression Scale), anxiety (Hospital Anxiety and Depression Scale), PiB‐PET measurements of cortical Aβ and FTP‐PET measurements of entorhinal cortex (EC) and inferior temporal (IT) tau prior to the pandemic. In May 2020, participants completed online surveys to determine living circumstances (alone vs. with others) and to re‐assess loneliness. Linear regressions with backward elimination estimated the interactive effect of living alone and either PiB, unilateral EC FTP, IT FTP, or PACC with change in loneliness (Δ Loneliness), adjusting for age, sex, time since pre‐COVID‐19 assessment, and pre‐COVID‐19 depression, anxiety, and loneliness.ResultTable 1 presents sample characteristics. Before May 2020, pre‐COVID‐19 loneliness levels did not differ between participants living alone or those living with others (t [103] = ‐1.77, P = 0.08). Participants living alone during COVID‐19 reported greater increases in loneliness compared to those living with others, adjusting for covariates (β = 1.22, P = 0.024). Greater right EC and IT FTP binding in individuals living alone was associated with greater increases in loneliness (for living alone*EC FTP: β = ‐4.31, P = 0.044; R2 = 0.18; for living alone*IT FTP: β = 7.45, P = 0.019; R2 = 0.20; Figure 1). Interactions of PiB and PACC with living alone predicting change in loneliness were not significant.ConclusionGreater tau pathology compounded the association of living alone with increases in loneliness in cognitively unimpaired older adults during the COVID‐19 pandemic. AD pathological brain changes may be an unrecognized factor which contributes to late‐life loneliness.
Bridging Oral Health and Alzheimer’s Risk: The “Mouth to Mind” Project
Authors: Chamut Steffany , Dye Bruce A. , Igwe Akwaugo , Low Spencer , Rahman Salman , Tabkhi Hamed , Au Rhoda 
Published: January 2025

AbstractBackgroundGlobal health is increasingly burdened by oral diseases (ODs) affecting 3.9 billion people, and Alzheimer’s disease with related dementias (AD/ADRD), impacting 46.8 million globally. Both are expected to increase due to aging populations and greater tooth retention. With soaring dental costs highlighting economic implications and complexities in access to care, there is an urgent need for early diagnosis and preventative low‐cost and accessible interventions. The “Mouth to Mind” project aims to develop and validate a comprehensive oral‐jaw health assessment tool that identifies early signs of cognitive impairment, focusing on the impact of jaw‐occlusal dysfunctions and exploring the intersection of oral health with neurodegenerative risks, malnutrition, and equity.MethodA questionnaire, part of an oral‐jaw health assessment tool, is being validated with a cohort of participants aged 40 and above (n = 23) who are part of a larger study providing feedback on different health technologies. Qualitative analyses are being used to evaluate the tool’s feasibility and clinical utility. Key outcomes include participant burden, measured by questionnaire completion time, and suggestions for improving questions and answers to enhance clarity and usability.ResultsThe study presents 20 females and 3 Males across diverse ethnic and racial groups (n = 8 Whites; n = 4 Hispanics; and n = 11 Black or African American) from the Greater Boston area. Anticipated results will be supportive of a validated questionnaire with insights into its administration, informing the design of a non‐invasive, user‐friendly tool for non‐dental settings.ConclusionsThis study lays the groundwork for the “Mouth to Mind” tool, aimed at early detection of oral diseases and jaw‐occlusal dysfunctions. By integrating oral health into the broader spectrum, it addresses cognitive decline risks. The next phase involves linking jaw‐occlusal dysfunction data with malnutrition and AD/ADRD risks, fostering the development of a transformative digital oral‐cognitive health tool. This tool is expected to advance early detection and preventive care, enhance life quality across populations, and drive significant policy and economic improvements in healthcare management.
Association Between Myocardium Hypertrophy And Dementia: A Population Based Autopsy Study
Authors: Silva Heberti Eliakim , Paradela Regina Silva , Leite Renata Elaine Paraizo , Pasquallucci Carlos Augusto , Grinberg Lea T. , Nitrini Ricardo , Jacob‐Filho Wilson , Suemoto Claudia Kimie 
Published: January 2025

AbstractBackgroundHypertension is a midlife modifiable risk factor for dementia. Uncontrolled hypertension is related to brain damage that could result in cognitive impairment, and one way of evaluating uncontrolled hypertension through life is assessing left ventricular hypertrophy (LVH). Previous imaging studies have shown a relationship between LVH and cognitive impairment. However, no previous study has evaluated this association using direct measurements obtained through autopsy. Furthermore, little is known about this relationship in diverse populations in low and middle‐income countries like Brazil, where the prevalence of dementia is expected to be higher than in high‐income countries. This study aimed to evaluate the association between LVH and dementia using data from an autopsy study in an admixed sample.MethodWe used data from the Biobank for Aging Studies of the University of São Paulo Medical School. The diagnosis of hypertension was obtained through a structured interview with an informant close to the deceased. The LVH was defined based on anatomical analysis and the left ventricular free wall measurement. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. The analyses were performed using regression models adjusted for sociodemographic and clinical confounders.ResultIn 1067 participants (mean age 70.6±11.9 years old, mean education 4.6±3.8 years, 46.2% women, 66.4% White), LVH was not associated with cognitive abilities in multivariate analyses adjusted for aged, education, sex, race, diabetes, heart disease, body mass index, smoking, alcohol use, and physical inactivity. Age, sex, education, and race did not modify this relationship.ConclusionWe did not find an association between LVH and cognitive impairment in our sample. Further analyses will be important to investigate the possibility of attrition bias.