bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in prevalence and incidence of dementia and their contributing risk factors by algorithmic classification: Results from the Health and Retirement Study
Authors: Tarraf Wassim , Garcia Marc A , Kuwayama Sayaka , González Hector 
Published: December 2023

AbstractBackgroundStudies that use observational population level data with research classification for dementia have to contend with error in classification. Errors might be particularly pronounced in studies examining racial and ethnic disparities in dementia where classification can be confounded by certain risk factors (e.g. Socioeconomic Status; SES).MethodWe use data from the health and retirement study to examine differences in dementia prevalence (in 2000 [n = 6,860] and 2016; [n = 6,892]) and 2‐year incidence (2000‐2002 and 2016‐2018) over two time periods between non‐Hispanic White (NH‐W) and NH‐Black older adults (ages 70+‐years) across 4 algorithmic classifications of dementia in HRS (Langa‐Weir, LASSO, Hurd, and Expert). We then use Oaxaca‐Blinder decomposition techniques to examine the contribution of lifecourse factors (demographic, childhood SES and health, adult SES, and later life health behaviors, and health characteristics) to these racial differences in prevalence and incidence over the two time periods.ResultAll four algorithmic classifications point to consistent differences (favoring NH‐W) in prevalence (Figure 1) and, to a lesser extent, incidence (Figure 2) of dementia. Additionally, dementia prevalence but not incidence decreased, particularly among NH‐B, between 2000 and 2016. Despite these consistent findings, the estimated rates of dementia prevalence and incidence differed depending on the algorithmic choice with the Lange‐Weir classification consistently underestimating rates for NH‐W. Nearly 3/4th of the differences in dementia prevalence between NH‐B and NH‐W were explained by advantageous (among NH‐W) adult SES factors, and later life health behavior, and health characteristics; with SES status consuming the largest share. The contributions of these factors were less notable for differences in dementia incidence.ConclusionAssessments of racial disparities in dementia with observational data, where cognitive and physical health and function measures are used to generate research classifications, can lead to varying estimates by choice of algorithm. Sensitivity to algorithmic classification is more notable for dementia prevalence estimates, particularly given SES confounding, than for incidence. Later life health and health behaviors are also notable drivers of racial differences in dementia prevalence. More work is required to calibrate classification techniques to reduce bias and enhance the precision in estimates of magnitude and risks for dementia disparities.
Perceptions of Brain donation and Medical Research Among African American Individuals: Implications for Recruitment and Retention into Alzheimer’s Research
Authors: Starks Takiyah D. , Caban‐Holt Allison M , Cuccaro Michael L. , Ford Tayla , Lloyd Shawnta' , Adams Larry D. , Haines Johnathan L , Reitz Christiane , Vance Jeffery M. , Pericak‐Vance Margaret A. , Byrd Goldie S. 
Published: December 2023

AbstractBackgroundAfrican Americans (AAs) are twice as likely to have Alzheimer’s disease (AD) as their White counterparts; yet, this population is largely missing from brain donation research. According to the National Alzheimer’s Coordinating Center, merely 2% of brain donations are obtained from AAs. Medical mistrust among AAs has been well‐documented as a barrier to medical research participation. The purpose of this study was to expand our understanding of AA perceptions of medical research and brain donation.MethodUsing validated survey items, a 35‐item cross‐sectional survey was developed to understand attitudes and beliefs about medical research and brain donation among AAs. Surveys were administered via REDCap (Research Electronic Data Capture) and paper in Florida, New York, North Carolina and Ohio, United States from November 2021 to September 2022. Descriptive analysis of data on research participation and trust in medical research was conducted using SAS® software version 9.4.ResultA total of 227 AAs participated in this study with about three‐quarters of participants being female. Approximately 90% of AAs reported being born in the US, and nearly half of the sample reported receiving some college education or higher. Only 10.6% of participants reported being very likely to donate their brain to research after death. Despite the low percentage of AAs willing to donate their brain to research, 77.1% had a positive view of medical research and 72.7% trusted researchers in general. In fact, participants perceived that it is “very important” to participate in medical research to help future generations (78.4%), to learn more about AD (66.5%), and receive medical information (56.8%).ConclusionMost AAs in this study reported strong trust in medical research and researchers. Medical mistrust may not be a significant barrier to participation in brain donation or AD research for AAs in this sample. Improved health literacy in AD research and brain donation procedures may facilitate engagement of AAs to participate in such research. Findings from this study will be used to inform the development of a culturally relevant health literacy program, with a focus on brain donation and AD research, to enhance opportunities for recruitment and retention of AAs.
The Luci program: a coach‐based online intervention to reduce dementia risk factors
Authors: Lussier Isabelle , Guillemont Juliette , Laroque Flavie M , Bacon Simon L , Boivin Michel , Ferland Guylaine , Lavoie Kim , Paré Guy , Belleville Sylvie 
Published: December 2023

AbstractBackgroundA large body of evidence indicates that behavioural interventions on modifiable risk factors for dementia can reduce cognitive decline in at‐risk older individuals. There is growing interest in making such interventions more widely accessible using technology‐based solutions. However, online programs would benefit from incorporating coach‐based interventions, the feasibility of which needs to be demonstrated. Luci is an online, coach‐supported, multidomain lifestyle intervention aimed to improve cognitive health in older adults at risk of cognitive decline. A pilot study was conducted to establish the feasibility of the program.MethodA web‐App was designed to allow 1‐1 coaching sessions, create and monitor personalized action plans, provide information on brain health, and collect outcome measures. 119 cognitively healthy, community‐dwelling individuals aged 50‐70 with ≥1 lifestyle risk factor (physical activity, diet, cognitive engagement) were recruited in this 24‐week, randomized (Luci vs. wait‐list controls), single‐blind pilot feasibility study. Main eligibility criteria included no severe health conditions (e.g., neurocognitive, psychiatric), to be French‐speaking, available for the duration of the program, and computer literate with access to a device and Internet. Adherence, retention rates, and satisfaction and usability were assessed. Secondary measures included change from baseline in lifestyle risk factors and cognitive performance.ResultParticipants had a mean age of 60.6 (SD = 5.6) and 16.7 (SD = 3.4) years of education; 84.9% were female. Retention and adherence rates were 92.4% and 84.5%, respectively, and a 3.7% difference in attrition rates between the intervention and control groups was observed. Program satisfaction and App usability rates were high, with over 95% agreeing that the coach helped them identify the benefits of and obstacles to changing their lifestyle and respected their opinion. A greater proportion of participants (1.3 to 2.7‐fold) in the intervention versus control group reached a clinically significant change in lifestyle risks. In contrast to the control group, the Luci intervention group showed improvements in cognitive performance.ConclusionProviding coach‐based online intervention programs might represent a powerful approach to support durable lifestyle changes in older adults at‐risk for dementia. The results from this study support the Luci program potential as a feasible intervention for effective and sustainable behavioural changes.
Aerobic exercise and volumetric change in the human hippocampus: A meta‐analysis of randomized controlled trials in healthy older individuals
Authors: Balbim Guilherme Moraes , Silva Nárlon Cássio Boa Sorte , Brinke Lisanne F Ten , Falck Ryan S , Hortobágyi Tibor , Granacher Urs , Erickson Kirk I. , Hernández‐Gamboa Rebeca , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundThere is promising, albeit equivocal, evidence that aerobic exercise training (AET) increases human hippocampal volume. The evidence is unclear, as recent randomized controlled trials (RCTs) have failed to replicate AET’s previously reported favorable effects on hippocampal volume in cognitively unimpaired older individuals. We thus conducted a meta‐analysis of RCTs investigating the effects of AET on hippocampal volume and cardiorespiratory fitness (CRF) in cognitively unimpaired, healthy older individuals.MethodA meta‐analysis of RCTs that delivered AET interventions to older individuals. Inclusion criteria were: 1) cognitively unimpaired, healthy individuals aged ≥ 50; 2) AET intervention delivered for at least four weeks; 3) at least one intervention group and one control group; 4) reported data of the effects of AET on hippocampal volume. Two authors independently screened titles, abstracts, and full texts, performed data extraction and methodological quality assessment of included studies. We performed meta‐analyses with random‐effects robust variance estimation models and meta‐regression analyses to test associations between changes in CRF and hippocampal volume. The primary outcome was changes in hippocampal volume, and the secondary outcome was changes in CRF.ResultEight parent trials and one secondary outcome article were eligible. The meta‐analytic summary of 17 effect sizes indicated no significant effects of AET on hippocampal volume (SMD = 0.10, 95%CI ‐0.01 to 0.21, p = 0.073). Meta‐analysis of nine studies and effect sizes showed that AET moderately improved cardiorespiratory fitness (SMD = 0.30, 95%CI 0.12 to 0.48, p = 0.005). Improvement in CRF was not statistically associated with changes in hippocampal volume (bSE = 0.05, SE = 0.51, p = 0.923). Methodological quality was poor in one, fair in three, good in four, and excellent in one trial.ConclusionAET did not show robust effects on hippocampal volume in cognitively unimpaired, healthy older individuals. Since AET significantly improved CRF, a lack of training fidelity is unlikely to explain our findings. The biologically still plausible favorable effects of AET on hippocampal volume in cognitively unimpaired older individuals might be masked by methodological weaknesses and the inclusion of only nine studies. Future studies need to address: the lack of harmonization of hippocampus quantification methods and insufficient power to detect meaningful changes in hippocampal volume across studies.
Cortical thickness is influenced by bilingual language dominance in typical and pathological cognitive aging
Authors: Grasso Stephanie M , Lucas Fernando Llanos , Petersen Melissa , Downer Brian , Milani Sadaf Arefi , Mehta Neil 
Published: December 2023

AbstractBackgroundPrior research in clinical and non‐clinical populations demonstrates that speaking more than one language can modify gray matter structure (e.g., DeLuca et al., 2020; Torres et al., 2022). However, existing work has largely classified bilingualism dichotomously, diminishing the ability to establish associations between bilingual factors (e.g., language dominance) and regional cortical thickness (CT).MethodWe examined cross‐sectional differences in CT across a large, ethnically diverse sample of bilingual and monolingual older adults from the Health and Aging Brain Study: Health Disparities cohort (n = 1,605; O’Bryant et al., 2021). Differences in CT between language dominance subgroups across three levels of diagnostic phase (cognitively unimpaired, mild cognitive impairment (MCI), and Alzheimer’s dementia (AD)) were evaluated using linear‐mixed effects models. Participants were characterized as English‐dominant or Spanish‐dominant speakers according to responses on language interview questions and the Short Acculturation Scale for Hispanics (Marin et al., 1987).ResultAssociations between CT and language dominance differed across diagnostic phase (Tukey‐adjusted ps <0.05). In the cognitively unimpaired group, English‐dominant speakers exhibited greater CT than Spanish‐dominant speakers in in regions‐of‐interest (ROIs) related to auditory processing (Heschl’s gyrus), semantic processing (temporal pole), and executive functioning (frontal pole). Spanish‐dominant speakers exhibited greater CT than English‐dominant speakers in two ROIs supporting motor (precentral) and spatial processing (entorhinal). These CT differences were attenuated in the MCI phase. Here, English‐dominant speakers exhibited greater CT than Spanish‐dominant patients in the frontal pole (executive processing). Spanish‐dominant patients did not exhibit greater CT than English‐dominant patients. Notably, this pattern of group differences was reversed in AD patients. Here, Spanish‐dominant patients exhibited greater CT than English‐dominant patients in ROIs in Alzheimer’s disease‐related regions (parahippocampal and entorhinal).ConclusionOur results indicate associations between language dominance and regional CT, with distinct patterns by diagnostic phase. Whereas English‐dominant bilinguals demonstrated greater regional CT relative to Spanish‐dominant bilinguals in the cognitively unimpaired and MCI phase, Spanish‐dominant bilinguals had greater CT in disease‐related regions in the AD phase. The presence of greater CT in Spanish‐dominant bilingual AD patients is suggestive of resistance to pathological progression. Future research examining longitudinal patterns of neural decline in larger samples is needed.
Longitudinal trajectories of myelin loss in the context of Alzhiemer’s disease biomarkers, glial activation, and APOE4
Authors: Stephenson Henry G. , Kohli Akshay , Kecskemeti Steven R , Rubinski Anna , Ewers Michael , Alexander Andrew L , Deming Yuetiva , Ma Yue , Van Hulle Carol A. , Langhough Rebecca E , Jonaitis Erin M. , Dean Douglas C , Ulland Tyler K. , Chin Nathaniel A. , Okonkwo Ozioma , Betthauser Tobey J , Asthana Sanjay , Kollmorgen Gwendlyn , Carboni Margherita , Wild Norbert , Carlsson Cynthia M , Johnson Sterling C , Blennow Kaj , Zetterberg Henrik , Bendlin Barbara B 
Published: December 2023

AbstractBackgroundLower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longitudinal changes in quantitative R1 (qR1), a marker sensitive to myelination obtained via MPnRAGE MRI.MethodParticipants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (ADRC) were selected based on available longitudinal MPnRAGE, clinical diagnosis, and APOE genotyping (N = 446). A subset (N = 141) included those with available baseline CSF (AB42/40, pTau181), and gliosis markers (sTREM2, GFAP, YKL40) measured using a robust prototype assay as part of the Roche NeuroToolKit research platform (Roche International). Longitudinal mean qR1 was estimated from white matter regions from the ICBM‐DTI‐81 atlas. In the overall sample, linear mixed effects models predicting regional qR1 (FDR‐corrected) with random intercepts and slopes were estimated controlling for sex, age centered within‐subjects (agec), age averaged within‐subjects (agegm), cognitive impairment, and APOE4 carriage as covariates. Two‐way interactions between impairment and APOE4 with agec were tested in the overall sample as were moderating effects of CSF amyloid‐positivity, pTau181, and gliosis markers on agec in the CSF sample.ResultIn the overall sample, older agec, agegm, and female sex were associated with lower qR1 in a majority of tracts indicating substantial longitudinal declines in qR1 over time and lower qR1 with advanced age and female sex. Sex, impairment, and APOE4 did not show significant agec interactions. Likewise, none of the CSF biomarkers moderated the effect of agec in the CSF subsample.ConclusionWhile aging is robustly associated with longitudinal demyelination as potentially indexed by qR1, these rates do not appear to be moderated by AD pathology, cognitive impairment, APOE4, or glial activation in early disease. Given the capacity for re‐myelination in the context of injury, longitudinal studies are critical for parsing myelin and AD relationships. Established associations between myelin and AD risk may reflect later disease processes, particularly in samples more enriched for tau pathology.
Diagnostic accuracy of cognitive assessment in diverse older adults: effects of normative sample and demographic adjustments
Authors: Tsoy Elena , Corrada María M. M. , Deters Kacie D , Medina Luis Daniel , Pa Judy , Tommet Douglas , Vila‐Castelar Clara , Whitmer Rachel A. , Gilsanz Paola , Mungas Dan M. 
Published: December 2023

AbstractBackgroundRacial and ethnic disparities in ADRD diagnosis are well documented but remain poorly understood. Clinical ADRD diagnosis relies on neuropsychological assessment, which is interpreted by comparing individual performance to demographically adjusted reference group norms. Differential use of demographic adjustment procedures and sources of normative data may compromise diagnostic accuracy of neuropsychological findings in diverse individuals. Using two different demographic adjustment approaches derived from two distinct normative samples, we generated cognitive impairment categories and evaluated their associations with longitudinal trajectories of independent executive functioning and memory scores.MethodParticipants were 717 older adults (age: 77.5±6.9, 56% women) enrolled in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study who completed up to 3 annual visits. The main predictor was cognitive impairment category (no impairment, single‐domain, multiple‐domain) based on Uniform Data Set Neuropsychological Battery (UDSNB) scores at baseline. UDSNB scores were either demographically unadjusted or adjusted (age, sex, education, and race/ethnicity) using data from the National Alzheimer’s Coordinating Center (NACC; N = 8313, 16% Black, 84% White) or KHANDLE (N = 397, 26% Asian, 18% Black, 30% LatinX, 26% White) samples. Linear mixed effect models were used to examine the associations between differentially derived cognitive impairment categories with longitudinal changes on episodic memory and executive functioning composites from an independent cognitive battery (Spanish and English Neuropsychological Assessment Scales, SENAS).ResultCognitive impairment categories derived from the KHANDLE sample were more strongly associated in all four racial and ethnic groups with longitudinal decline on episodic memory compared to the NACC sample‐derived categories (Figure 1). Similar, albeit attenuated, effects were observed in relation to longitudinal decline on the executive function composite. There were no clear differences in the associations between cognitive impairment categories with executive functioning or memory decline using demographically adjusted vs. unadjusted scores.ConclusionOur results highlight the need for greater representation of diverse individuals in normative samples underlining the limitations of the NACC‐derived normative algorithms for cognitive assessment of individuals from diverse populations. Further investigations into the clinical value of the practice of demographic adjustments are also warranted.
Effects of Mutations in Tau’s Proline Rich Region on Epileptic Activity and Sleep in Mouse Models of Epilepsy
Authors: Vicente Mariane Cristine , Vaknalli Rahil , Anderson Ashley J. , Stepter Joshua S , Onanyan Nane , Narasani Anushka , Ravishankar Sahana , Western Ava W , Thayer Stanley , Vossel Keith , Vaknalli Rahil 
Published: December 2023

AbstractBackgroundGenetic ablation of tau prevents seizures, memory loss, and premature mortality in transgenic mouse models of Alzheimer’s disease, but the exact mechanisms are unknown. We tested the hypothesis that variants in tau’s proline rich domain, which affect binding to SH3‐containing proteins, prevent epileptic activity in epilepsy models.MethodWe used the following lines: 1) AxxA6 (P‐to‐A substitutions in 6th PxxP motif in tau) and 2) R221A: R‐to‐A substitution at amino acid corresponding to 221 in human 2N4R tau. Tau knockout mice were used as a benchmark. We injected kainic acid (25 mg/kg, ip), and analyzed latency to different seizure severity levels (SSL) over 3 hours: 1 to grade 8. We also crossed AxxA6 and R221A mice with the Kv1.1 knockout (Kcna1–/–) model of epilepsy and performed 24‐hour epidural video‐electroencephalography and electromyography in mice ages 5‐8 weeks. We used ex vivo slice electrophysiology and measured burst frequency in CA3 after bath‐applied picrotoxin and 4‐amino‐pyridine.ResultTau knockout mice exhibited higher latency to seizure stages than wildtype mice (WT) after kainic acid injections (p<0.05, One‐way ANOVA), consistent with previous studies. Heterozygous AxxA6 mice showed reduced susceptibility to seizures (n = 4‐6 per genotype; SSL 4‐8: ∼ 9.5 vs WT: 4.5 seconds, p<0.05, One‐Way ANOVA). The heterozygous R221A tau variant decreased mortality in Kcna1 KO mice (p<0.05). Epileptic spikes in Kcna1 KO mice averaged 22 spikes/hour (AxxA6 n = 4, R221A n = 7), and AxxA6 (homozygous and heterozygous) tau variants decreased epileptic activity to ∼2 spikes/hour (p<0.05, One‐Way ANOVA, excluding statistical outliers) in Kcna1 KO mice. Kcna1 KO mice showed a higher percentage in the awake state during light and dark phases compared to WT mice (n = 5, p<0.05, t‐test). The AxxA6 and R221A tau variants did not alter sleep‐wake cycle in Kcna1 KO mice. Kcna1 KO mice showed increase burst frequency in CA3, and heterozygous and homozygous R221A tau variants reduced bursting frequency (p<0.05, One‐Way ANOVA).ConclusionThe AxxA6 and R221A tau lines show partial reduction in seizure susceptibility in models of epilepsy compared to the tau knockout line. The tau protein variants do not affect regulation of the sleep‐wake cycle in the Kcna1 model.