bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep Duration and Cognitive Performance in Middle‐Aged and Older Adults: What is the Role of Depression?
Authors: Young Vanessa M. , Bernal Rebecca , Baril Andree‐Ann , Zeynoun Joy , Wiedner Crystal , Beiser Alexa S , Pase Matthew P. , Himali Jayandra J. , Seshadri Sudha 
Published: January 2025

AbstractBackgroundRecent research has highlighted the importance of sleep on cognitive processes. However, conflicting evidence exists regarding optimal sleep duration and the impact of other co‐occurring conditions, such as depression. A diagnosis of depression in mid‐life may increase the risk of developing dementia. We examined the association between self‐reported sleep duration and cognition and whether depression status modified this relationship.MethodDementia‐and‐stroke‐free participants 45 years and older from the Framingham Heart Study Third‐Generation, Omni 2, and New Off‐spring Cohorts were included (n = 1,853; age 49.8[SD 9.2] years; 42.69% male; Table 1). Neuropsychological testing assessed verbal learning and memory abilities, abstract reasoning skills, processing speed and visuospatial memory. Depression was defined as having CES‐D ≥16 or being under pharmacological treatment (n = 448; 32%). Multivariable linear regression models examined the association between sleep duration categories (≤6h; >6‐<9h [reference]; ≥9h), individual cognitive tasks and global cognition, adjusting for age, sex, education and time between sleep and cognitive assessments. A second model included further adjustment for vascular risk factors and APOE4 status.ResultLong sleep duration (≥9h) was associated with worse global cognition (β±SE: ‐0.24±0.07; p<0.001) compared to average sleep duration. In cognitive domain‐specific tasks, long sleep was associated with worse verbal learning and memory abilities (‐1.50±0.60, p = 0.013), visuospatial memory (‐1.74±0.42, p<0.001), and processing speed (‐0.08±0.03, p = 0.014), but not with abstract reasoning skills (‐0.06±0.28, p = 0.838). Depression status significantly modified the association (global cognition int. p = 0.015; visual int. p = 0.006; and processing speed int. p = 0.038), where long sleep duration was associated with global cognition (‐0.34±0.11; p = 0.003), visuospatial memory (‐2.16±0.68; p = 0.002), and processing speed (‐0.14±0.05; p = 0.011) in those with depression. Long sleep duration was also associated with visuospatial memory in those without depression (‐1.27±0.55, p = 0.022) (Table 3). Short sleep duration (≤6h) was not associated with cognition (Table 2) and did not interact with depression status (Table 3).ConclusionLong sleep duration was associated with worse cognition particularly among adults with depression, underscoring the complex sleep‐mood‐cognition interplay. Further research should explore the longitudinal impacts and causal mechanisms of suboptimal sleep. These findings may inform public health promotion of optimal sleep to maintain cognitive health among persons with depression.
Mild Behavioral Impairment is associated with incident cognitive decline among dementia‐free, racially diverse older adults: Data from the African Americans Fighting Alzheimer’s in Midlife (AA‐FAIM) study
Authors: Fischer Barbara L. , Van Hulle Carol A. , Norton Derek L. , Wyman Mary F. , Ennis Gilda E. , Zuelsdorff Megan L. , Lambrou Nikolaus H , Bouges Shenikqua , Gooding Diane Carol , Gleason Carey E. 
Published: January 2025

AbstractBackgroundMild behavioral impairment (MBI) is associated with all‐cause dementia. Little is known about MBI’s effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American (AA) older‐middle aged adults. AA participants were enrolled in African Americans Fighting Alzheimer’s in Midlife (AA‐FAIM), an ancillary study of the Wisconsin Disease Research Center’s (WADRC) Clinical Core.MethodAnalytic sample included participants without dementia, with ≥1 study visits and measures of cognitive/clinical function. A baseline MBI rating (present/absent) was derived using study partners’ report of neuropsychiatric symptoms at two consecutive visits, (i.e., two consecutive positive MBI scores = MBI present). Cognitive outcomes included measures of speed, mental flexibility and memory.ResultTable 1 provides characteristics by MBI status for white (N = 450), AA (N = 100), and other underrepresented group (URG) (N = 34) participants. In the full sample, baseline MBI significantly moderated cognitive trajectory on Trails B, though not on any other tasks. Participants with MBI displayed worse trajectory of decline on Trails B relative to those without MBI (Figure 1). Additionally, MBI at baseline significantly predicted progression to cognitive impairment CDR >0 (HR est: 2.84; HR 95% CI: 1.68 — 4.81; p = 0.0001) (Figure 2). Stratified analysis in a smaller AA subgroup showed a similar pattern but was not significant.ConclusionMBI associated with more adverse cognitive trajectory and predicted incident cognitive decline in older, middle aged participants without dementia. Our findings highlight the importance of identifying MBI as a possible target for intervention in early disease stages. A fifth of our sample (21.5%) identified as Black/URG. Still, ongoing work in inclusive cohorts is needed to better understand MBI in under‐represented groups.
Diminished awareness, rather than hyperawareness, is more indicative for the progression along the Alzheimer’s clinical continuum, already in the subjective cognitive decline.
Authors: Incesoy Enise I , Düzel Emrah ,   DELCODE study group
Published: January 2025

AbstractBackgroundAnosognosia is a frequent phenomenon in Alzheimer’s dementia. Both heightened and decreased awareness of cognitive decline (AoCD) have been observed in mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Despite some studies, the association between altered awareness and clinical conversion remained unclear. This study investigates the impact of AoCD on the conversion to incidental MCI (iMCI) and dementia within clinical high‐risk groups in the DELCODE study.MethodAnnually collected longitudinal data from 405 SCD and 163 MCI participants (4.33 ±1.99 years) were used. Awareness was assessed using two scores: AoCDinf (discrepancy between participant and informant reports from the SCD‐Interview) and AoCDobj (discrepancy between participant‐report and dichotomized objective test scores). Participants were categorized into hyperaware (AoCD > 0), N‐aware (AoCD = 0), and unaware (AoCD < 0) groups. Cox proportional hazard regression models predicted the effect of awareness group on progression to iMCI and dementia. Analyses were adjusted for age, sex, education, MMSE, and diagnostic group.Resultsa. MCI conversion: 109 (27%) SCD participants converted to iMCI (2.90±1.76 years). Non‐converters demonstrated more heightened initial awareness for both scores, even after adjusting for covariates (only for AoCDobj: F[5, 397] = 28.29, β = 0.224, p<.0001). Hyperawareness in SCD was associated with reduced risk of progression to MCI compared with diminished awareness (Hazard Ratio (HR)inf = 0.57, 95% CI: 0.34‐0.98, p = .04; HRobj = 0.25, 95% CI: 0.15‐0.42, p<.0001). b. Dementia conversion: 78 (14%) SCD+MCI participants converted to dementia (3±1.95 years). Converters exhibited significantly lower initial awareness in both scores, even after adjusting for covariates (Fobj[5, 562] = 47.79, β = 0.231, p<.0001; Finf[5, 534] = 17.63, β = 0.132, p<.01). Unawareness in the nondemented clinical group was associated with higher risk of progression to dementia compared with hyperawareness (HRinf = 2.26, 95% CI: 1.23‐4.15, p = .009; HRobj = 3.35, 95% CI: 1.40‐8.03, p = .007).ConclusionUnawareness of cognitive decline is related to a decreased risk of conversion to dementia in the clinical population. Specifically, in SCD, diminished awareness, rather than hyperawareness, is more indicative of progression to MCI. Informant reports and minor cognitive deficits in SCD provide valuable insights, emphasizing their importance in clinical settings and pharmacological trials.
Digitizing the Trails Making Test for Automatic Detection of Cognitive Impairment: Validity and Reliability
Authors: Toro‐Serey Claudio , Higgins Connor , Banks Russell , Jannati Ali , Tobyne Sean , Showalter John , Pascual‐Leone Alvaro 
Published: January 2025

AbstractBackgroundThe Trail Making Test (TMT) is one of the tests most commonly included in neuropsychological batteries to assess executive functions. A digitized version of TMT would provide objective measurements of time to complete (TTC) and total number of errors (TE) with minimal training, and eventually enable process metrics including detailed evaluation of drawing behavior. Here we evaluated the test‐retest reliability and validity of a new digital TMT Part B (dTMT‐B).MethodWe examined cognitively unimpaired participants from two clinical trials: DCT216 (N = 182, age mean±SD = 64.8±7.5; 60% female; years of education mean±SD = 14.4±2.5; 20% Hispanic; 3‐5 weeks between tests) and Bio‐Hermes‐001 (N = 342, age mean±SD = 70.5±6.4; 63% female; years of education mean[IQR] = 16[14‐23]; 6% Hispanic). For both TTC and TE, reliability was assessed via intraclass correlation coefficients (ICC 3, k) in DCT216. Internal consistency was evaluated using Cronbach’s alpha. We assessed validity by combining visit 1 of DCT216 and Bio‐Hermes‐001 and performing a multiple linear regression predicting TTC using predictors for study, age, sex, education, ethnicity, and interactions between study and each demographic. Specifically, we calculated the coefficients for age (key demographic in paper‐based TMT) and for demographic performance across both studies.ResultICCs showed great reliability for TTC (0.87, 95% CI = 0.83 ‐ 0.90, p < 0.0001) and good reliability for TE (0.65, 95% CI = 0.53 ‐ 0.74, p < 0.0001). Cronbach’s alpha showed good internal consistency across these metrics as well (0.68). For validity, we found the expected significant main effect of age (T = 7.48, p < 0.001) and no significant interactions (p > 0.05), suggesting similar trends with paper‐based TMT‐B and consistent TTC values across studies.ConclusiondTMT‐B is a valid and reliable digital implementation of the commonly used, paper‐based TMT Part B.
Expanded bile acid annotations linked to diet and AD biomarkers
Authors: Mohanty Ipsita , Caraballo‐Rodriguez Andres Mauricio , Zemlin Jasmine , Labus Jennifer S , Dorrestein Pieter , Kaddurah‐Daouk Rima F. ,   Alzheimer’s Gut Microbiome Project Consortium (AGMP)
Published: January 2025

AbstractBackgroundBile acids (BA) are steroids regulating nutrient absorption, energy metabolism, and mitochondrial function, and serve as important signaling molecules with a role in the gut‐brain axis. The composition of BAs in humans changes with diet type and health status, which is well documented with a few known bile acids. In this study, we leveraged a new BA‐specific spectral library curated in the Dorrestein lab at UCSD to expand the pool of detected BAs in Alzheimer‐related LC‐MS/MS datasets and provide links to dietary profiles and AD markers.MethodFecal untargeted metabolomics (LC‐MS/MS) data from the ADRC cohort was analyzed using GNPS‐based molecular networking. Spectral matching and annotation were performed using the BA‐specific spectral library which consists of 21,549 BA spectra, with many previously undiscovered candidates. We obtained spectral matches to 113 BAs with 108 matches to new candidate BAs from our library. Further, using the score for delayed recall of Benson figure (UDSBENTD), peak areas of the BAs were plotted with the amyloid status. For diet readout, spectral match to a food database (“global foodomics”) was performed, and correlation with BAs was obtained by joint‐RPCA analysis.ResultThe joint‐RPCA analysis yielded many di‐, tri‐, and tetrahydroxylated BAs among the top 20 features guiding the separation in the ADRC samples (Figure 1a). From diet, meat, fish, and fruits were among the top features, with meat and fish vectors pointing in the opposite direction as grapes, onions, and lettuce. Peak area‐based levels of a candidate tetrahydroxylated BA, which was among the top 20 features, changed with the amyloid status measured with the UDSBENTD (Figure 1b). The spectral count of vegetables and dairy also increased in amyloid‐positive samples. However, the spectral counts related to meat and poultry products did not change significantly with amyloid status, implying a potential vegetable‐based diet impacting the change in some BA levels.ConclusionPreviously unknown BAs are correlated to diet and AD markers in the ADRC cohort. This study highlights the importance of expanding our metabolite annotations, in this case with BAs, and performing integrative analysis with diet to aid our understanding of AD progression.
Longitudinal Neuropsychiatric Symptom Trajectories in Frontotemporal Dementia: From Presymptomatic to Symptomatic Conversion
Authors: Lee Hyunwoo , Scott Imogene M , Chatterjee Atri , MacKenzie Ian R , Lapid Maria I. , Huey Edward D. , Tartaglia Maria Carmela , Kantarci Kejal , Rankin Katherine P. , Rosen Howard J. , Boeve Brad F. , Boxer Adam L. , Hsiung Ging‐Yuek Robin ,   the ALLFTD Consortium
Published: January 2025

AbstractBackgroundFrontotemporal dementia (FTD) presents with heterogeneous neuropsychiatric symptoms (NPS). These symptoms often begin prior to the onset of FTD, and progress throughout the prodromal stages of FTD. Particularly, familial FTD due to autosomal dominant genetic mutations might display mutation‐specific NPS profiles. We hypothesized distinct NPS trajectories for chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule‐associated protein tau (MAPT) mutation carriers during their transition from presymptomatic to symptomatic stages of FTD.MethodIn this study, we analyzed N = 1662 participants from the ARTFL‐LEFFTDS Longitudinal FTLD (ALLFTD) Study, with 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We used the CDR plus NACC FTLD global scores to define the conversion status, and stratified participants into four stages of progression: 1) Presymptomatic (CDR = 0 throughout the follow‐up), 2) Early conversion (began with CDR = 0, then increased to 0.5), 3) Advanced conversion (began with CDR = 0.5, then increased to 1.0 or above), and 4) Symptomatic (CDR>1.0 throughout). Over up to seven visits, the Neuropsychiatric Inventory Questionnaire (NPI‐Q) assessed changes in NPS. We analyzed total NPI‐Q score trajectories using a generalized linear mixed‐effects model, adjusting for age and baseline NPI‐Q scores.ResultOur findings showed similar NPS trajectories among carriers and noncarriers during presymptomatic stages. However, in the early conversion stage, C9orf72 and GRN carriers exhibited significantly higher NPI‐Q score increases compared to MAPT carriers, primarily in the psychosis and hyperactivity domains. In the advanced and symptomatic stages, the rate of increase in NPS was not significantly different across groups.ConclusionThis study suggests that people with familial FTD, particularly those predicted to have underlying TDP‐43 pathology, may experience more severe neuropsychiatric symptoms like psychosis or hyperactivity as they progress from presymptomatic to prodromal phases. This trajectory appears distinct from those with tau pathology or sporadic FTD. Further studies are warranted to understand these unique progression patterns and their implications for FTD management.
Inclusion and attrition in the community‐based cohort of functional decline of elderly with cognitive complaint of the Geroscience Center for Brain Health and Metabolism
Authors: Parrao Teresa , Saguez Rodrigo , Thumala Daniela , Lillo Patricia , Demanet Michele , Amieva Helene , Martínez‐Pernía David , Zitko Pedro , Cerda Mauricio , Muniz‐Terrera Graciela , Slachevsky Andrea 
Published: January 2025

AbstractBackgroundCognitive complaints (CC) refer to a reported experience of cognitive decline and are recognized as a potential precursor to future functional decline and progression to dementia. Identifying individuals with CC may be a valuable opportunity for preventive measures, early detection, and intervention strategies to address dementia risk. However, the characteristics of CC and its associated risk of progression to dementia are highly heterogeneous, influenced significantly by CC identification methods, recruitment approaches, and attrition in longitudinal cohort studies. This study aims to inform the inclusion and attrition processes of the GERO cohort.MethodThe GERO cohort is a prospective cohort study of community‐dwelling elderly individuals with CC without dementia, aged 70 or older, living in Santiago, Chile. In this study, two samples were analyzed (dropout and non‐dropout groups) using logistic regression to assess the variables associated with attrition. Binary logistic regression analyses were conducted with dropout as the outcome variable. Prior to the multivariable models, univariate analyses were performed.ResultOut of 17,759 households approached, we successfully recruited 291 participants. Of the individuals initially recruited, 102 participants withdrew before the first follow‐up assessment. The results showed that the non‐dropout group (64.9%) was characterized by being younger (OR: 1.09; 95% CI: 1.04‐1.14), had better cognitive status according to the MoCA test (OR: 0.92; 95% CI: 0.87‐0.98), had better functionality according to the T‐ADLQ (OR: 1.08; 95% CI: 1.04‐1.12), better performance in instrumental ‐IADL‐ (OR: 1.06; 95% CI: 1.03‐1.09) and advanced ‐aADL‐ (OR: 1.03; 95% CI: 1.01‐1.04) dimensions, and better performance on the ECOG test (OR: 2.56; 95% CI: 1.13‐4.53) compared to the dropout group (35.1%). In the multivariate logistic regression model, dropout was associated with the performance of instrumental activities of daily living IADL (OR: 1.05; 95% CI: 1.01‐1.09), whereas the other variables did not exhibit statistical significance (Table 1).ConclusionThe rate of participants included, considering the number of households approached, inform on the difficulties to recruit participants with CC in the community. Functionality in daily life emerged as the key factor associated with the risk of dropout. Furthers research is needed to understand the role of functionality in CC.
Persistent Heart Rate Variability Deficits Among Dementia Patients With History of Excessive Alcohol Use
Authors: Elegores Marianne T , Patel Shivani , Elmi Sarah 
Published: January 2025

AbstractBackgroundPrevious literature has highlighted that excessive alcohol use (EAU) is directly linked with permanent neurological damage. Studies have also highlighted gradual improvements in heart rate variability (HRV) after cessation of alcohol use. Moreover, chronic alcohol consumption has also been correlated with reduced HRV and an increase in skin conductance (SC) among healthy adults, leading to a combined decline in cognitive performance. This study examines the persistence of HRV and SC changes among older adults with dementia and a history of alcohol use disorder (AUD).MethodParticipants were recruited from the Geriatric Transitional Unit at Ontario Shores Mental Health Sciences, Whitby, Ontario. Eligibility included a formal diagnosis of dementia and history of lifelong EAU was recorded based on informants. Behavioral and symptoms of dementia was assessed with the Neuropsychiatric Inventory Clinician rating scale. Empatica E4 wristbands was used to record physiological data. Physiological signals such as electrodermal activity (EDA) and heart rate (HR) were recorded. HRV was analyzed using KUBIOS software. T‐tests were used to determine differences in frequency and severity of BPSD, HRV and SC.Result28 participants were recruited, 17 male, average age: 73.4, 10 had EAU history (average age 67.8, 2 female). EAU group had a significantly lower root mean square of successive differences (RMSSD) (p = 0.002) and parasympathetic nervous system (PNS) activity (p = 0.021), but significantly higher sympathetic nervous system activity (SNS) (p = 0.007) than participants without EAU. Additionally, the standard deviation of normal beats (SDNN) and RMSSD scores of EAU group were below the normal range. Moreover, EDA was higher in participants without EAU (M = [1.54], SD = [3.46]) compared subjects with EAU (M = [0.43], SD = [0.94]), but the difference was not significant (p = 0.36). There was no statistically significant difference between NPI scores of the 2 groups.ConclusionOur findings indicate that alcohol abuse results in long‐term alterations of peripheral nervous system, causing an increase in sympathetic activity and a consequent decrease in parasympathetic activity. We observed that EAU subjects have a diminished ability to vagally mediate heart rate.
Variable Sleep Quality Is Related to Tau Burden and Worse Memory in Older Women at Risk for Alzheimer’s Disease
Authors: Stiver Jordan , Wang Xin , Lui Kitty K. , Dratva Melanie A , Heyworth Nadine , Pa Judy , Malhotra Atul , Sundermann Erin E. , Banks Sarah 
Published: January 2025

AbstractBackgroundWomen are more likely to experience sleep problems than men, especially during and after menopausal transition. Sleep disturbances are related to memory decline and the development of Alzheimer’s disease (AD), which is also more common among women. While research on habitual sleep patterns in aging has largely focused on mean sleep outcomes across nights, few studies have examined the potentially harmful effects of night‐to‐night variability in sleep quality on AD biomarkers and memory function. The purpose of this study was to determine how intraindividual variability in nocturnal sleep quality relates to tau burden and memory function in older women at elevated genetic risk for AD.MethodsOlder women (N = 33; Mage = 73.1, SD = 4.0; APOE‐ε4 carriers, n = 17) with mild cognitive impairment and an AD polygenic hazard score ≥50%ile wore an actigraphic device on the wrist for an average of 7.6 nights (range = 5‐13) to objectively measure sleep behavior. Participants also completed neuropsychological tests and 18F‐MK6240 tau‐PET to quantify tau burden. Variability in wake time after sleep onset (WASOv) was calculated as the intraindividual standard deviation of WASO across sleep intervals. Memory was assessed using delayed recall scores from the Logical Memory (LM) subtest of the Wechsler Memory Scale‐Revised, the Rey Auditory Verbal Learning Test (RAVLT), and the Brief Visuospatial Memory Test‐Revised (BVMT‐R). A composite tau‐PET temporal meta‐region of interest was calculated based on standardized uptake value ratios using inferior cerebellar gray matter as the reference region.ResultsAfter controlling for age, APOE‐ε4 carrier status, and mean WASO, regression models showed that WASOv predicted greater meta‐temporal tau‐PET signal (β = .52, p<.05) and worse delayed recall on LM and BVMT‐R (β = ‐.58 and β = ‐.63, respectively; ps<.01). Results further showed interaction effects, such that WASOv was associated with greater tau as well as worse RAVLT and BVMT‐R performances, especially among APOE‐ε4 carriers (|β| range = .67–.89, all ps<.05).ConclusionsVariability in sleep quality is associated with greater tau burden and worse memory function in older women at risk for AD, particularly among APOE‐ε4 carriers. Results highlight the possibility that variable sleep quality is a modifiable risk factor in the early pathogenesis of AD and its cognitive sequelae.