bluuebunny/crossref_metadata_2025_split huggingface dataset:
County‐level indicators of education quality and brain imaging markers of neurodegeneration and vascular injury among racially and ethnically diverse middle‐aged and older adults
Authors: Roscoe Joseph , Whitmer Rachel A. , Gutierrez Sirena , Eng Chloe W. , Glymour M. Maria , Decarli Charles , Barnes Lisa L. , Gavett Brandon E , Gilsanz Paola 
Published: January 2025

AbstractBackgroundEarly‐life education quality has been associated with dementia risk and late‐life cognitive functioning. However, the association between education quality and neuroimaging outcomes remains unclear.MethodsThese analyses utilized data from 450 participants in two harmonized cohorts of racially and ethnically diverse adults aged 50 years and older (KHANDLE and STAR) who completed brain Magnetic Resonance Imaging and whose self‐reported school location at 9th grade could be linked to historical educational quality data from the National Center for Education Statistics. Three county‐level indicators of 9th grade education quality were categorized into tertiles based on the pooled dataset and treated as ordinal variables with the lowest tertile serving as the reference: percent attendance, teacher‐student ratio (number of teachers per 30 students), and term length. Measures of gray matter volume, hippocampal volume, white matter hyperintensity volume (log‐transformed), and ventricular volume (log‐transformed) were residualized on total cranial volume. Linear regression models with robust standard errors estimated associations between education quality measures and each imaging marker, adjusting for age at imaging, demographics, childhood socioeconomic status, study cohort, and history of racial segregation in state of 9th grade education. Sensitivity analyses examined each education quality measures separately, adjusting for covariates.ResultsHigher teacher‐student ratio was associated with greater gray matter volume (β = 6.25, 95% CI: 1.57, 10.92) but was not associated hippocampal volume (β = ‐0.01, 95% CI: ‐0.14, 0.11), ventricular volume (β = ‐0.04, 95% CI: ‐0.13, 0.04), or white matter hyperintensity (β = ‐0.02, 95% CI: ‐0.31, 0.26) (Table 2). Higher percent attendance was associated with greater ventricular volume (β = 0.10, 95% CI: 0.03, 0.18) but was not associated with gray matter volume (β = ‐3.12, 95% CI: ‐7.07, ‐0.82), hippocampal volume (β = ‐0.06, 95% CI: (‐0.17, 0.05), or white matter hyperintensity (β = ‐0.02, 95% CI: ‐0.26, 0.22). Term length was not associated with any marker of neurodegeneration or vascular brain injury. Results were similar when examining each education quality measure separately.ConclusionsCounty‐level teacher‐student ratio and percent attendance, markers of education quality, had qualitatively different associations with imaging markers of neurodegeneration. Additional studies in larger samples are needed to confirm and better understand underlying reasons for these potential differences.
Frailty and risk of delirium among UK Biobank participants
Authors: Cai Ruixue , Gao Chenlu , Zheng Xi , Hu Kun , Gao Lei , Li Peng 
Published: January 2025

AbstractBackgroundDelirium is a common neurological complication in older adults after a major illness or surgery and is characterized by acute dysfunction in cognition, attention, and awareness. Once diagnosed, it is associated with an increased risk for dementia. Frailty is an age‐related syndrome and is associated with poorer postoperative outcomes, and is an emerging risk factor for delirium. The current study aimed to examine the association between frailty and delirium risk in middle‐ to older‐aged adults.MethodWe examined frailty and incident delirium in 389,040 UK Biobank participants (38‐73 years old; 178,377 females) were hospitalized at least once during follow‐up. Frailty at baseline was assessed using two validated measures: (1) frailty phenotype (FP) that is identified when three or more of the following five criteria were fulfilled: self‐reported weight loss, exhaustion, low physical activity, slow walking pace, and low grip strength; (2) frailty index (FI: range 0‐1) that is calculated from 49 items covering health, presence of diseases and disabilities, and mental well‐being (FI score ≥0.24 indicating frailty). A new onset of delirium was obtained from hospitalization records using ICD‐10 F05 coding. Cox proportional hazards models assessed the association between frailty and delirium.ResultAt baseline, 4.3% (15,311/359,979) and 5.2% (20,061/389,040) were identified as frail cases using FP and FI, respectively. The participants had been followed for a median of 12 years, with 6,710 newly developed delirium cases. Compared with non‐frail participants based on FP, participants with frailty were at a higher risk for delirium after adjusting for age, sex, ethnicity, and education (Hazard ratio [HR] = 3.22, 95% CI = 2.97‐3.49, p<0.0001). Similar results were observed based on FI, i.e., frail participants had an adjusted HR of 2.79 (95% CI = 2.59‐3.00, p<0.0001) for delirium compared with non‐frail participants. These observations were consistent after further adjusting for social economic status, body mass index, sleep duration, smoking, and alcohol consumption (HR = 2.48, 95% CI = 2.28‐2.70 for FP; HR = 2.17, 95% CI = 2.01‐2.35 for FI, both p values <0.0001).ConclusionFrailty predicted delirium in middle‐ to older‐aged adults. Assessment and management of frailty may help with risk stratifications for delirium.
Cognitive functioning and markers of immune and neural dysfunction in Post‐acute sequelae of COVID‐19
Authors: Reynolds William Cody , Abril Isabel , Quiñones‐Alvarado Raymond , Arnold Steven E , García‐Beltrán Wilfredo F , Guzman‐Velez Edmarie 
Published: January 2025

AbstractBackgroundOver 65 million COVID‐19 survivors grapple with lasting neurological and cognitive symptoms that persist for months or years after infection, known as neuro‐Post‐acute Sequelae of COVID‐19 (neuro‐PASC). These symptoms are amongst the most common and incapacitating and are hypothesized to represent a heighted risk for neurological disease. Yet, little is known about the pathophysiological mechanisms underlying neuro‐PASC. Here, we examined whether worse neuro‐cognitive functioning was associated with markers of immune and neural dysfunction.MethodsWe report data for 55 people with PASC (average age = 46.09) and 37 healthy controls (HC; average age = 42.84). PASC participants were never in the ICU, 68% female sex, and infected an average of 471.27 days pre‐enrollment. HCs were 57% female sex and 15 were infected an average of 647.73 days pre‐enrollment but fully recovered. We assessed subjective cognitive decline using the Measurement of Everyday Cognition (ECog), memory with the RBANS list learning, and executive functioning with the Trail‐Making Test B (TMT‐B). PASC participants completed a self‐report questionnaire of PASC symptom severity. We measured plasma levels of CX3CL1/Fractalkine, a marker of immune function, and Ubiquitin C‐terminal hydrolase‐L1 (UCH‐L1), a marker of neural function. We conducted t‐tests and linear regressions adjusting for age.ResultsNeurological symptoms were amongst the most severe. Headaches, insomnia, and brain fog were rated as the ones that interfered the most with daily activities. Compared to HCs, PASC participants reported worse subjective memory, language, planning, organization, and attention decline. There were no significant group differences on cognitive test scores. PASC participants exhibited significantly higher CX3CL1/Fractalkine and UCH‐L1, although the latter was not significant when controlling for age. Those with higher levels of CX3CL1 exhibited higher levels of UCH‐L1, indicating a relationship between immune and neural dysfunction. Elevated UCH‐L1 levels were associated with worse TMT‐B performance, but not CX3CL1.ConclusionsFindings show that neurological symptoms, including subjective cognitive decline, are highly prevalent and severe in PASC. There was clear evidence of heightened inflammation potentially from endothelial cells, and of neural injury, which was associated with worse executive functioning. Therefore, immune dysregulation and neural injury may be underlying neuro‐PASC, and potentially contributing to greater risk for brain disease.
Ten Year Patterns of Change in HbA1C and Risk of Dementia in a Diverse Cohort of Adults with Type 2 Diabetes
Authors: Whitmer Rachel A. , Moran Chris , Costales Brianna , Tsai Ai‐Lin , Lacy Mary E , Karter Andrew , Gilsanz Paola 
Published: January 2025

AbstractBackgroundThough high HbA1c (marker for glycemic control) is associated with increased dementia risk, the influence of longitudinal changes in HbA1c is unclear. We examined the association between 10‐year trajectories of HbA1c and dementia risk in a large, diverse sample of people in Northern California.MethodIn a cohort of 32, 914 patients with Type 2 diabetes aged ≥ 50 years, we obtained repeated measures of HbA1c, dementia diagnoses, and comorbidities from electronic medical records (EMR) from 1996‐20021. We identified 5 latent trajectories of yearly mean HbA1c over a 10‐year period (Figure 1): Group 1‐HbA1cconsistently <7; Group 2‐ HbA1c consistently close to 7; Group 3‐moderate HbA1c peaking late between 7‐9; Group 4‐moderate HbA1c peaking early between 7‐9; Group 5‐ HbA1c consistently between 9‐11. Cox proportional hazards models estimated the association between HbA1c trajectories and incident dementia ≥5 years after the end of the exposure period adjusting for age (as timescale) and prevalent health conditions (Table 1) at the beginning of the trajectory period. Stratified models examined possible effect modification by sex or race/ethnicity.ResultApproximately half of the sample were women (Table 1). The most common trajectory was Group 2‐consistently close to 7 (47%), followed by Group 1‐consistently <7 (35%), Group 3‐moderate peaking late (9%), Group 4‐moderate peaking early (7%), and Group 5‐ consistently high (3%). Compared to Group 1, Groups 3‐5 had elevated risk of dementia (Figure 2); risk was comparable in Groups 3 and 4 (HRGroup3 = 1.30 (1.14, 1.48) and HRGroup4 = 1.28 (1.10, 1.49)) and was highest in Group 5 (HR = 1.78 (1.42, 2.26). Group 2 was not at elevated dementia risk compared to Group 1 (HR = 1.02 (0.94, 1.09). These associations did not vary by sex or race/ethnicity.ConclusionOver a 10‐ year period, consistently elevated HbA1c levels ≥ 9 are associated with an 80% elevated risk of dementia compared to those with a trajectory of HbA1c 6‐7. Those whose trajectory included HbA1c levels of 8‐9 either early (Group 4) or late (Group 3) in the10‐year period had approximately 30% increased risk. These results suggest that there are long‐term consequences of elevated HbA1c even if levels subsequently decrease.
Bidirectional associations between blood pressure and memory decline over 25 years: a 1946 British Birth cohort population‐based study
Authors: James Sarah‐Naomi 
Published: January 2025

AbstractBackgroundMidlife blood pressure is a risk factor for cognitive impairment. Yet, the directional relationship between blood pressure and memory may vary across adulthood, be confounded by earlier life factors, and vary by sex. Using a population‐based cohort of people born in the same week, we investigate the bidirectional associations between diastolic blood pressure (DBP) and memory, spanning over 25 years of adulthood.MethodData from participants (n = 1922, 52% female) in the British 1946 birth cohort were included. DBP and Word Learning Test (WLT) performance were assessed at four points across adulthood (ages 43, 53, 60 and 69) by nurse visits. WLT incorporated three 15‐item word recall (summed to give a maximum score of 45) with alternating lists across assessments. Autoregressive cross‐lagged models assessed the bidirectional associations between WLT and DBP. Models were tested for sex effect modification and adjusted for childhood cognition; childhood socioeconomic position; education; and hypertensive medication use.ResultThe autoregressive cross‐lagged models revealed an independent unidirectional relationship between higher DBP in midlife predicting lower subsequent cognition (i.e. higher DBP at age 43 predicting lower memory at age 53; higher DBP at age 53 predicting lower memory at age 60 and 69, additively) (Figure 1). In contrast, there was a unidirectional relationship between later‐life cognition (at age 60) predicting higher subsequent DBP (at age 69), with preliminary results demonstrating a stronger effect in women. In a sex‐adjusted model, a 1 SD higher memory score at age 60 was associated with 4mmMg increase in DBP at age 69. Adjusting for childhood cognition, childhood SEP and education largely attenuated these effects but results mainly remained significant at the 5% level.ConclusionWe provide evidence that higher midlife blood pressure is associated with subsequent lower memory, in line with previous studies, and even after adjustment for strong predictors of cognition, such as childhood cognition, education and SEP. However, our results also demonstrate evidence of a reverse association later in life, whereby lower memory is associated with subsequent lower blood pressure suggesting that cognitive processing may play a role in diastolic ageing processes, particularly in women.
Trends in Diagnosis of Dementia Subtypes in Nationwide Medicare Claims, 2015‐2021, by Race/Ethnicity, Sex, and Neighborhood Socioeconomic Status
Authors: Lusk Jay B , Ford Cassie B , Blass Beau , Johnson Kim G , Clark Amy G , Soneji Samir , O'Brien Richard J , Hammill Bradley G , O'Brien Emily C 
Published: January 2025

AbstractBackgroundIt is not well understood how incidence patterns of subtypes of Alzheimer’s disease and related dementias (ADRD) have evolved in real‐world practice. While cohort and brain bank studies provide precise biological definition of ADRD subtypes, these populations may not be representative and may not reflect how dementia is coded and diagnosed in routine clinical practice. Therefore, we sought to perform a nationally representative study of medical claims data to understand trends in diagnosis of dementia by dementia subtypes in routine clinical practice.MethodWe studied 100% of nationwide Medicare claims from 2014‐2021 and evaluated dementia diagnoses by specified subtypes with associated international classification of diseases (ICD) codes (Alzheimer’s disease, vascular, Lewy body, frontotemporal, alcohol induced, and not otherwise specified). We stratified results by age, sex, race/ethnicity, and neighborhood socioeconomic deprivation measured by the area deprivation index, a well‐established score that describes neighborhood socioeconomic conditions. Incidences are presented as number of new cases per 10,000 person‐years. Race/ethnicity were grouped as White, non‐Hispanic; Black, non‐Hispanic; and other race/ethnicity, concordant with other Medicare claims data analyses.ResultA total of 5,721,711 patients with incident dementia were included in the study. Dementia diagnoses were more frequently coded as vascular in 2021 than 2015 (1.85 cases per 10,000 person‐years in 2015 vs 2.21 cases per 10,000 person‐years in 2021) and less frequently coded as not otherwise specified (29.1 cases per 10,000 person‐years in 2015 vs 22.17 cases per 10,000 person‐years in 2021). Coding by dementia subtype varied by race (Table 1) and sex (Table 2). Dementia diagnoses were much more frequently coded as “not otherwise specified” among beneficiaries from socioeconomically deprived neighborhoods (34.48 per 10,000 person‐years in the most deprived decile vs 25.76 in the least‐deprived decile) (Table 3).ConclusionIn a national database of Medicare claims, there were substantial secular trends and differences in coding of dementia subtypes by race/ethnicity, sex, and neighborhood socioeconomic status. Secular trends in coding could reflect variation in health system performance of accurate diagnosis of dementia subtypes. Future studies should correlate claims data classifications with confirmed neuropathological classifications.
Assessing Clinical Research Barriers to the Participation of Underrepresented Groups in the AHEAD Study
Authors: James Taryn T. , Gleason Carey E. , Gooding Diane Carol , Carter Fabu P. , Cardenas Cecilia A. , Deering Olivia , Cole Aleshia , Cronin Kate , Carlsson Cynthia M. , Bouges Shenikqua 
Published: January 2025

AbstractBackgroundTo increase participation of underrepresented groups (URG) into clinical research studies such as the AHEAD study, a study assessing lecanemab in participants with preclinical Alzheimer’s disease (AD), it is necessary to understand and address barriers in an effort to mitigate them. Toward this goal, methods assessing community needs and plans to meet those needs are imperative. Our ultimate goal is to aid URG in understanding the clinical research process and to empower them to participate in AD research so that approved therapies are applicable to them.MethodThis work was made possible by an AHEAD Diversity Recruitment Supplement grant funded to University of Wisconsin‐Madison (UW‐Madison) by the Alzheimer’s Clinical Trial Consortium (ACTC) to increase URG participation in the AHEAD study. Our approaches include using surveys to identify barriers in order to develop a strategic plan to overcome them. Surveys assessed whether potential participants had knowledge of 1) lecanemab, 2) the AHEAD study, and 3) if they would be comfortable in a study involving a medication, among others. Interested individuals were rewarded with a swag bag for completing the surveysResultThe findings showed that URG were not likely to be aware of lecanemab or the AHEAD study. Additionally, while they wanted to know if they met the criteria for the study, they were less comfortable about a clinical study involving a medicine (Figures 1). Moreover, we identified other barriers to research participation, such as factors that were more likely to prevent URG from meeting study criteria. These included not knowing family history or their AD biomarker status, which was necessary inclusion criteria for individuals age 55‐64 (Figure 2).ConclusionSurveys at community events are useful in identifying barriers to the engagement of URG in AD clinical trials. To decrease barriers and push the pendulum towards increased participation of URG in biomedical research, increased educational efforts are needed on AD, the clinical trial process, and drug development. Moreover, researchers must make sure that URG are not ruled out from the study onset, meaning inclusion criteria must consider some unknown challenges such as not knowing medical or family history.
Investigating Individual and Familial Stress on Alzheimer’s Disease among a Global Cohort of Non‐Hispanic Blacks and Hispanic/Latinos
Authors: Moise Rhoda , Cai Dingtian , Rajabli Farid , Hamilton‐Nelson Kara L. , Adams Larry D. , Cuccaro Michael L. , Kunkle Brian W. , Vance Jeffery M. , Reitz Christiane , Tosto Giuseppe , Bush William S. , Haines Jonathan L. , Byrd Goldie S. , Akinyemi Rufus O. , Ogunniyi Adesola , Blanton Susan Halloran , Pericak‐Vance Margaret A , Seixas Azizi A , Consortium Africa Dementia 
Published: January 2025

AbstractBackgroundStress has emerged as a risk factor in the development and progression of Alzheimer’s Disease (AD). However, there is limited research on the impact cumulative individual and familial stress has on AD. This study aims to investigate the relationship between stress and AD within a global cohort of underrepresented populations including Black Americans (BAs), Hispanic/Latinos (H/Ls), and Africans (As).MethodThe total sample size was N = 328. Binomial regression in R examined the stress‐AD association, controlling for age, sex, race/ethnicity, and site. Stress was defined as “a situation in which a person feels tense, restless, nervous, or anxious, or is unable to sleep at night because his/her mind is troubled all the time.” Individuals were asked 1) Do you feel this kind of stress these days? and 2) While growing up did you and your family experience stress? Participants rated stress on a 0‐4 Likert scale. Binary recoding distinguished low (not at all) and high stress (all else). Ethnicity was coded as H/Ls and Non‐Hispanic Black Utilizing the binomial family, the analysis robustly explored the relationship between stress and AD diagnosis.ResultsA quarter of the sample (mean age = 73.53, SD = 8.63) had AD, while most had no cognitive impairment (mean age = 71.13, SD = 6.88). 73% were females (N = 240). Low‐stress individuals are 1.812 times more likely to be non‐cognitively impaired (p = 0.03767). Familial stress is not significant (p = 0.83255). Although there were significant results for ethnic group and age, their interpretation captures the distribution of cases and controls within those groups. Our experimentation was not designed to test them, but the inclusion of these variable in the model serve to adjust for the main variable of interest, stress.ConclusionThis study reveals the stress‐AD link in a diverse population, emphasizing the necessity of targeted interventions considering individual stress in cognitive health research, urging further exploration of familial stress and ethnicity nuances. Understanding these relationships is crucial for tailored support systems and preventive strategies. Future research should delve deeper into stress as a modifiable AD risk factor, exploring underlying mechanisms for a comprehensive understanding. Additionally, future studies should design to further explore age and ethnicity in AD prediction.
Preclinical Alzheimer Disease pathology in studies of memory and aging
Authors: McKay Nicole S. , Millar Peter R , Barthélemy Nicolas R. , Benzinger Tammie L.S. , Morris John C. , Bateman Randall J. , Schindler Suzanne E. , Gordon Brian A. 
Published: January 2025

AbstractBackgroundPreclinical Alzheimer disease (AD) describes a period prior to symptom onset during which pathology begins to accumulate. Recent development of neuroimaging‐ and biofluid‐ measures of AD pathology has allowed for in vivo quantification of preclinical pathological burden. Prior work estimated that by age 85, only one third of older adults remain free of amyloid and AD‐related atrophy.MethodHere, using complementary multimodal biomarkers of AD pathology, we aimed to reproduce and extend these estimates of preclinical AD prevalence in a cohort of cognitively unimpaired (Clinical Dementia Rating = 0) older adults (demographics in Figure 1). We included neuroimaging‐derived measures of amyloid and neurodegeneration (cortical amyloid, cortical thickness, summary tau), as well as biofluid‐derived measures of non‐specific AD pathology (amyloid42:40, phosphorylated‐tau217, neurofilament light). Gaussian mixture modelling defined the probability of biomarker positivity, which we examined as a function of age (Figure 1).ResultOur results reproduce and extend prior estimates of AD pathology in cognitively unimpaired older adults, confirming in our independent sample that AD pathology is present in cognitively unimpaired individuals. Cerebrospinal fluid‐derived measures of amyloid peaked at a rate close to 60%, but all measures of amyloid and neurodegeneration were observed to rise to be present in at least 40% of cognitively unimpaired older adults. Unsurprisingly, tau was observed at the lowest rate, potentially reflecting its tight associated with cognitive impairment.ConclusionWe have replicated and extended prior reports of large proportions of older adults being afflicted by silent, preclinical, AD pathology. Rates of preclinical Alzheimer Disease pathology is important to estimate in large older adult cohorts so that these silent pathologies do not bias estimates of healthy aging. However, it is important to note that cohorts examining sporadic AD recruit individuals with family histories of AD and therefore have higher rates than average populations of apolipoprotein‐variant carriers, which may influence the rates of AD pathology. Characterizing the prevalence of preclinical AD is critical for understanding the pathophysiology of AD, may inform the design of clinical trials or interventions, and may also provide important context for furthering our understanding of cognition across older adulthood.