bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary analysis reveals links between visual attention, sleep duration, and neural recruitment in Alzheimer's disease
Authors: Rempe Maggie P , Springer Seth D , Garrison Grant M , Glesinger Ryan J , Okelberry Hannah J , Petts Aubrie J , Embury Christine M , Wilson Tony W 
Published: January 2025

AbstractBackgroundSleep disturbances have been shown to relate to the development of Alzheimer’s disease (AD) and its associated cognitive deficits, including visual attention function. Here, we investigated the potential interactive and additive effects of sleep disruption and AD on visual attention performance and its underlying neural mechanisms.MethodPreliminary analysis included 33 participants, 10 biomarker‐positive patients on the AD spectrum (mild cognitive impairment (MCI) and AD; 7 females; Mage: 70.24) and 23 cognitively‐healthy older adults (17 females; Mage: 67.47). Participants completed a visual search task during magnetoencephalography (MEG). Participants wore an Actigraph device on their non‐dominant wrist for a two‐week period. Actigraph data were cleaned using sleep diaries and analyzed using the Cole‐Kripke algorithm. Total sleep time (TST) was calculated for each night of sleep and averaged across all nights of sleep collected. The MEG data were transformed into the time‐frequency domain and significant task‐related oscillatory responses were source‐imaged.ResultBehavioral analysis of the visual search task revealed a significant conditional effect (p < .001) and a significant group by TST interaction (p < .001) on RTs, revealing overall longer RTs in conjunctive trials and longer RTs in patients on the AD spectrum with shorter TST. Regarding the MEG data, we observed robust neural responses in theta, alpha, and beta frequency bands. Analysis of source‐imaged neural responses in the alpha range revealed significant conditional differences in the right posterior temporal lobe (p < .005), such that stronger responses were found in the conjunctive condition relative to the feature condition. A significant group‐by‐condition interaction was found in the right temporoparietal junction (TPJ; p < .005), revealing that patients on the AD spectrum had weaker responses during the conjunctive condition compared to controls. Finally, a group by TST interaction on conditional differences in alpha power (p < .005) in right occipital and cerebellar regions revealed that the relationship between condition‐wise neural recruitment in these regions and TST differed as a function of AD diagnosis.ConclusionThese preliminary findings suggest key relationships between total sleep time, visual attention behavioral performance and neural recruitment, and how these relationships may differ in AD spectrum conditions.
Health care utilization and cost differences across cognitively‐defined Alzheimer’s disease subgroups
Authors: Coe Norma , Sun Chuxuan , White Lindsay , Shapiro Lily N , Taylor Janelle S , Crane Paul K. 
Published: January 2025

AbstractBackgroundExisting studies on the health care utilization and costs associated with Alzheimer’s disease (AD) have treated individuals with AD as a homogeneous group, though recent evidence suggests individuals with AD may be classified into biologically distinct subgroups with differing genetic and clinical profiles. The objective of our study is to examine differences in healthcare utilization and costs across cognitively defined AD subgroups.MethodWe utilize data from the Adult Changes in Thought (ACT) study (1994 – 2020), a population‐based longitudinal study of aging and the incidence of and risk factors for dementia. We focus our study on individuals who developed incident AD and classify these individuals into one of six cognitively‐defined AD subgroups using previously described methods. We identify a sex‐ and birth year‐matched set of controls using a many‐to‐one matching method. Controls are assigned an index date equal to the AD onset date for their matched AD case. We examine utilization and costs in the year preceding AD onset and in the three years following. Our utilization outcomes include number of days in a month spent in a hospital inpatient, intensive care unit, or skilled nursing facility setting, and number of emergency department visits. We also examine monthly total health care costs and component costs, including outpatient, hospital inpatient, skilled nursing facility, and pharmacy costs. We utilize repeated measures generalized estimating equations to estimate health care utilization associated with each AD subgroup. To estimate the incremental costs associated with each subgroup, we use the Basu and Manning cost estimator.ResultWe find significant utilization and costs differences across the cognitively‐defined AD subgroups, driven primarily by differences in the use of hospital inpatient and skilled nursing facility services. We also find the highest utilization and costs among the group of individuals with substantial relative impairments across multiple cognitive domains.ConclusionStudies on the health care utilization and costs associated with AD miss important heterogeneity by examining individuals with AD in the aggregate. Our study suggests that individuals in the cognitively‐defined AD subgroups have distinct health care utilization and cost patterns leading up to and following AD onset.
Self‐awareness of cognitive impairment in a community‐based cohort
Authors: Barrett A. M. , Ang Ting Fang Alvin , Liu Yulin , Devine Sherral A. , Mez Jesse , Au Rhoda , Lin Honghuang 
Published: January 2025

AbstractBackgroundThe deficit of unawareness of cognitive impairment (cognitive anosognosia) is known to be associated with adverse health outcomes, caregiver burden, and worse cognitive outcomes. A better understanding of cognitive self‐awareness and the ability to self‐judge cognitive performance among the general population would enable a rational design of cognitive screening and improve how subjective cognitive decline and self‐reported errors at tasks like medication administration are interpreted.MethodParticipants were enrolled in the Framingham Heart Study, which is a community‐based cohort with three generations of participants. Through ancillary studies, FHS participants underwent neuropsychological assessments every 4 to 5 years. For those with possible cognitive impairment, study examiners identified, and a panel later adjudicated, a clinical diagnosis (intact, mild cognitive impairment [MCI], or dementia, and their subtypes). Before the neuropsychological testing, participants were asked, “Do you have any concerns about your memory or thinking”. If “yes,” they were further asked: “Do you think this is normal for your age?”ResultOur study included 5,110 participants of FHS with self‐reported assessment of cognition (mean age: 67±15 years; 55.1% women, 66.2% with some college degree or above). As shown in Table 1, among 359 (7.0% of the participants) diagnosed with MCI or dementia, 47.4% (170) had a self‐report consistent with unawareness of cognitive impairment (72 or 45.0% of MCI, 98 or 49.2% of dementia). These individuals had NO self‐reported concerns at all about memory and thinking. Even more concerning, a larger group of people (p = 0.025) with MCI or dementia who DID self‐report concerns about memory/thinking (88 with MCI, or 55.0%, 101 with dementia, 50.7%), stated that they thought the problem was normal for their age (124 participants, 65.6%).ConclusionMost of the Framingham Heart Study participants clinically diagnosed with pathologic cognitive impairment self‐reported that they either had no memory or thinking problems, or, more often, self‐reported memory and thinking problems that they felt were normal for their age. This is consistent with cognitive anosognosia, which can represent a range of unawareness. Since subjective cognitive decline is used to identify MCI, further research could develop complementary MCI diagnosis markers.
The Effects of Aerobic‐Strength Training on Cognitive Functions and Residual Platinum Levels in Cancer Survivors
Authors: Ukropcová Barbara , Amiri Ali , Slobodova Lucia , Malenovská Karin Marček , Pechancova Radka , Rerkova Katarina , Schön Martin , Oliva Viktor , Litvakova Viera , Sedliak Milan , Krssak Martin , Pluhacek Tomas , Mego Michal , Chovanec Michal , Ukropec Jozef 
Published: January 2025

AbstractBackgroundThe risk of cognitive decline in cancer survivors may be increased by platinum‐based chemotherapy. Evidence indicates that physical exercise has a potential to reduce chemotherapy‐related toxicity. The aim of this study was to assess effects of a 6‐month aerobic‐strength training on cognitive functions, metabolic flexibility, anthropometric parameters and physical fitness in testicular germ cell tumor (TGCT) survivors, treated with platinum‐based chemotherapy.MethodsTGCT survivors underwent 6‐month intervention (supervised aerobic‐strength training/ controls n = 20/8, age 42.1±7.6 yrs. BMI:27.7±3.8kg/m², VO2max:29.2±6.7 mlO2/kg/min, 1‐20 years post‐treatment). Cognitive functions (FACT‐Cog; computerized tests Memtrax & CogState; Auditory Verbal Learning Test/AVLT), abdominal adiposity (MRI), cardiorespiratory fitness (VO2max, spiroergometry), muscle strength (leg‐press; chair dynamometry), energy expenditure and metabolic substrate preference (indirect calorimetry), serum glycemia, insulinemia, lipid profile, plasma adiponectin (ELISA), platinum, and zinc (Inductively‐Coupled Plasma Mass Spectrometry) were assessed before and after the 6‐month intervention.ResultsTraining improved delayed and short‐term memory recall (AVLT), compared to non‐active controls. Training‐induced changes in delayed memory recall positively correlated with improvements in VO2max, supporting a link between cognition and cardiorespiratory fitness. Training reduced visceral adiposity (p<0.01), increased HDL‐cholesterol (p<0.01), cardiometabolic fitness (VO2max) and muscle strength (both p = 0.01). Plasma adiponectin, glycemia and insulinemia were unaffected by exercise training (p>0.1), while intervention normalized residual plasma platinum and increased zinc levels (both p<0.01), with no change in controls. Platinum levels (P<0.001) and number of chemotherapy cycles (p = 0.06) were the best predictors of memory function in cancer survivors.ConclusionsAerobic‐strength exercise training reduced visceral adiposity and circulating residual levels of platinum, improved physical fitness and cognitive functions in TGCT cancer survivors. Our observations support a role for exercise as an effective complementary treatment for cancer survivors, with a potential to reduce residual chemotherapy burden and cardiometabolic risk, which could be linked to improved cognitive functions.Funding: APVV 19‐0411, VEGA2/0164/20, VEGA 2/0076/22
Adverse childhood events and the timing of Alzheimer's Disease in Down syndrome
Authors: Hickey Emily J 
Published: January 2025

AbstractBackgroundPeople with Down syndrome (DS) are genetically at‐risk for Alzheimer’s disease (AD). The age of symptomatic AD in DS varies (late‐40s‐70s). Lifestyle factors are theorized to explain some of this variability. Experiencing adverse childhood events (ACEs) is associated with later‐life cognitive decline and risk for AD in general population samples. Mechanisms underlying this association may involve biological pathways such as systemic inflammation and/or increased mental health conditions such as anxiety and depression, which are themselves risk factors for AD. Little is known about the effect of ACEs on AD pathology (PET Aβ and tau) or symptomology directly, or indirectly through inflammation or mental health in DS.MethodsWe investigated ACEs prevalence in 112 adults with DS (mean age=39.0, range 25‐61; mild ID: 60.7%) and associations with plasma markers of inflammation, informant‐reported mental health, and PET Aβ and tau, controlling for age. Inflammation was measured by a composite of plasma IL‐6 (interleukins), serum IL‐6, serum CRP (C‐reactive protein), and serum sICAM (soluble intercellular adhesion molecule) levels. Mental health problems were measured via the Anxiety, Depression, and Mood Scale (ADAMS), Glasgow Depression Scale‐Caregiver Supplement (CGDS), and Reiss Screen for Maladaptive Behaviors (RSMB). Dementia symptoms were assessed via the Down Syndrome Mental Status Exam (DSMSE).ResultsEighty percent (n=90) of participants reported at least one ACE and 24% (n=27) reported ≥4. ACEs were positively associated with anxiety (t=2.35, p=.021), depression (t=2.64, p=.010), maladaptive behaviors (t=3.35, p=.001), and plasma inflammatory markers (t=2.40, p=.021), controlling for age. ACEs were not significantly associated with the DSMSE. ACEs were associated with tau (t=‐2.58, p=.013) and at a trend level, with Aβ (t=‐1.95, p=.057), controlling for age, although not in the expected directions.ConclusionsPeople with DS are vulnerable to ACEs and experience expected associations between higher ACEs and more mental health problems and systemic inflammation, but ACEs were not related to dementia symptoms. Unexpectedly, ACEs were related to lower PET Aβ and tau relative to age. It is possible that ACEs may be linked to other AD protective factors, such as time spent in the community. Future research should look into pathways that explain this finding.
Identifying early predictors of cognitive impairment and dementia in a large nationally‐representative US sample
Authors: Hudomiet Peter , Hurd Michael D , Rohwedder Susann 
Published: January 2025

AbstractBackgroundDementia impacts a large and growing number of older adults in the US, and the total impact of disease is costly to individuals and society. Though many risk factors have been identified, accurately predicting future dementia remains difficult. This study aims to identify early predictors of cognitive impairment and dementia using a large US sample.MethodWe evaluated the predictive power of 181 dementia risk factors using a recently developed and validated probabilistic measure of dementia and cognitive impairment, available on 97,629 person‐year observations in the nationally representative longitudinal Health and Retirement Study in the US (Table 1). The project predicted two types of outcomes: the two‐year or four‐year incidence of dementia or cognitive impairment; and the prevalence of dementia or cognitive impairment at age 80 based on the characteristics of individuals at age 60.ResultIn line with prior literature, physical health, a prior stroke, cognitive abilities, ADL and IADL functional limitations, and genes strongly predicted future incidence and prevalence of cognitive impairment and dementia. Our statistical models identified additional predictors that have received less attention. For example, dementia prevalence at age 80 was 9.9 percentage points higher (20.5% vs. 10.6%) among those with a BMI above 35 (vs. BMI 0‐25) at age 60, and this differential reduced to 4.2 ppts but remained statistically significant when all other predictors were controlled. Other factors associated with a higher chance of having cognitive impairment or dementia in the future were: being born in the South, not having a private health insurance plan at age 60, working fewer years, diabetes at age 60, never exercising, scoring lower on various physical performance measures (e.g. pulmonary function, grip strength, walking speed, balance tests), being less conscientious, and lower engagement in hobbies and novel information activities (Figures 1 and 2).ConclusionThe sharpened list of dementia risk factors can be used to raise awareness and target resources for prevention and early detection in the presence of health system capacity constraints. These results are suggestive that some behavioral changes and interventions might slow cognitive decline.
Unlocking Pragmatic Changes in Typically Aging Elderly: An In‐Depth Analysis
Authors: Akkunje Preetie Shetty , Archa Sasi kumar , Hegde Prasanna Suresh , Thaut Michael H 
Published: January 2025

AbstractBackgroundThe dual‐cyclical relationship between language and cognition, encapsulated in linguistic relativity, underscores the reciprocal influence of thoughts on communication and vice‐versa. This study explores the intricate changes in pragmatics, a fundamental aspect of human communication, during the aging process, considering changes in sensory abilities, cognition, and language.MethodSixty participants, aged ≥50 years with a minimum of five years of formal education, were included, excluding those with neurological or psychological illnesses. Participants were categorized based on Montreal Cognitive Assessment (<25 & ≥25 MOCA scores), and their demographic details, language use, and educational and occupational history were recorded. Pragmatic evaluations included 1) functional communication profile analysis (sensory, receptive language, expressive language, pragmatic language and non‐oral communication), 2) pragmatic language evaluation (verbal aspects, paralinguistic aspects, nonverbal aspects), 3) spontaneous speech evaluation using Western Aphasia Battery, 4) discourse production assessment (macrostructures–main concept analysis, correct information units, global coherence and microstructures–T unit), and 5) hearing evaluation (pure tone audiometry, speech audiometry). Statistical analysis employed SPSS version 29.0.10, utilizing descriptive statistics and Likelihood ratio or Chi‐square tests.ResultsParticipants had a mean age of 66.5±9.9 years, with 58.3% females and 41.7% males. Educational distribution included 31.7% with ≤10th standard, 13.3% with 12th standard, 46.7% with a Bachelor’s degree, 6.7% with a Master’s degree, and 1.7% with a Ph.D. Regarding language proficiency, 41.7% were proficient in one language, 53.3% in two languages, and 5% in three languages. Significant relationships between pragmatic characteristics were identified among participant groups, supporting existing literature linking cognitive‐linguistic decline to aging. Higher MOCA scores correlated with superior speech discrimination and communication, while lower scores were associated with hearing loss. Likelihood Ratio Tests indicated significant associations between higher MOCA scores (≥25) and clear, specific, stimulus‐related pragmatic communication, while scores below 25 were linked to pragmatic difficulties.ConclusionThe study highlights the robust connection between pragmatics, cognitive function, and hearing abilities in the elderly. It offers insights into communication disorders, advocating for integrated rehabilitation programs for individuals with cognitive decline and hearing loss. Additionally, it reveals the intricate relationship between education, cognitive abilities, and pragmatic skills, guiding clinical practice and intervention strategies.
Impact of Sleep on Extracellular Volume in Human Brains: A Study with Simultaneous Sodium (23Na) MRI and EEG
Authors: Chen Xingye , Lin Ying‐Chia , Kumbella Nahbila‐Malikha , Henin Simon , Rockowitz Zena , Liu Anli , Masurkar Arjun V. , Babb James , Ge Yulin , Lui Yvonne W. , Qian Yongxian 
Published: January 2025

AbstractBackgroundAlzheimer's disease is associated with neurotoxic amyloid‐beta (Aβ) plaques. Studies in mice demonstrated that cerebrospinal fluid (CSF) clearance, if impaired, reduces Aβ clearance by 70% and that sleep enhances CSF clearance via expanding extracellular space by 60%. However, the impact of sleep on extracellular volume in human remains unclear due to lack of non‐invasive technology. In this study, we use unique sodium (23Na) magnetic resonance imaging (MRI) to measure extracellular volume fraction (ECVF) in healthy subjects while monitoring their sleep stage with MRI‐compatible electroencephalography (EEG).MethodWith IRB approval, we studied 16 cognitively‐healthy subjects (age 52.9 ± 17.6 years, ranging 27–77 years, 7 males and 9 females). The study lasted 1.5 hours, including four repeated 16‐min sodium MRIs on a clinical scanner at 3T (Prisma, Siemens), and continuous EEG recording (Brain Vision, 32‐channel, Garner, NC). The subjects were instructed to relax and fall asleep. Sleep was scored to five stages (wake, N1, N2, N3, and REM), based on American Academy of Sleep Medicine (AASM) Manual (v2.6, 2020). Sodium MRI was performed with a dual‐tuned (1H‐23Na) birdcage coil (QED, Cleveland, OH) and a custom‐developed pulse sequence, twisted projection imaging (TPI), with parameters: FOV=220mm, matrix size=64, 3D isotropic, TE/TR = 0.5/100ms, flip angle=90°, averages=6, and TA=16min. ECVF, a
e, was calculated on the sodium images voxel‐by‐voxel, i.e., s = ΔV (aeCe + aiCi) = ΔV (145 ae + 15 ai), with ae + ai = 1.ResultIn panel P1 is the set‐up of the study, including the MRI, EEG, sodium images, and hardware set‐up. In P2 are typical EEG waveforms and spectra of sleep stages. In P3 is a representative of ECVF maps from a subject (43 years old, female). In P4 are outcomes of the study. Surprisingly, we observed a decrease in ECVF with sleep stage in the gray matter (P=0.036) and in the white matter (P=0.085, nearly significant).ConclusionThis study surprisingly observed a decrease in ECVF with sleep stage in the gray matter of healthy subjects, and in white matter as possible. This finding is contrary to the outcome from the animal studies and needs to confirm with more human subjects.
Development of a Multi‐task Graph Neural Network for Alzheimer’s Disease Drug Repurposing
Authors: Hsieh Kang‐Lin , Plascencia‐Villa German , Lin Ko‐Hong , Perry George , Jiang Xiaoqian , Kim Yejin 
Published: January 2025

AbstractBackgroundDeveloping drugs for treating Alzheimer’s disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.MethodTo address the challenge in AD drug development, we developed a multi‐task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi‐level evidence on drug efficacy, to identify repurposable drugs and their combination candidatesResultUsing the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post‐treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population‐based treatment effect, and Phase 2/3 clinical trials. We experimentally validated the top‐ranked candidates in neuronal cells, identifying drug combinations with efficacy in reducing oxidative stress and safety in maintaining neuronal viability and morphology. Our neuronal response experiments confirmed several biologically efficacious drug combinations.ConclusionThis methodology showed that harmonizing heterogeneous and complementary data/knowledge, including human interactome, transcriptome patterns, experimental efficacy, and real‐world patient data shed light on the drug development of complex diseases.