bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do patients in early‐stage cognitive impairment have an increased risk of developing sarcopenia? A cross‐sectional study
Authors: Lopes Pedro de Castro , Leopoldino Amanda Aparecida Oliveira , Machado João Carlos Barbosa , Barbosa Maira Tonidandel , Garcia Luana Rodrigues , Aguiar Bianca Pessoa , de Souza Júlia Caroline Barbosa , Ferreira João Pedro Neres Antunes 
Published: January 2025

AbstractBackgroundSarcopenia is a prevalent condition defined by a loss of muscle mass associated with reduction in muscle power and physical performance. It is associated with several adverse outcomes such as risk of falls and fractures, hospitalization and higher mortality. It can be triggered by several clinical conditions and dementia is one of them. Many studies point the relationship between cognition and sarcopenia, especially in advanced cases of dementia. However, more studies are necessary to understand whether patients with mild cognitive impairment have also increased risk for developing sarcopenia.MethodThis is a cross‐sectional study in which 87 community‐dwelling elderly people were included and evaluated in relation to the presence of cognitive impairment and sarcopenia. Patients with severe cognitive impairment, assessed by a score less than 6 in the CS‐10 (Point Cognitive Screening) were excluded. Individuals with a score between 6 and 7 on the CS‐10 were considered to have mild or moderate cognitive impairment and participants with a score greater than 7 on this test were considered to have no cognitive impairment. In order to evaluate the presence of sarcopenia it was applied the SARC‐F CC questionnaire. Those with a score greater than or equal to 11 were considered sarcopenic and a score between 0 and 10 without sarcopenia. With the aim of estimate the association between the characteristics, Pearson’s chi‐square test was calculated. If the p‐value was lower than the significance level of 0.05, it is possible to conclude the correlation between the development of sarcopenia and a worse score in CS‐10.ResultIn the sample studied, 29.1% were classified with an increased risk for sarcopenia. The mean CS‐10 score was 8.2 with a standard deviation of 1.7 points. Patients with higher SARC‐F CC scores had a lower mean score on the CS‐10, but these results did not show a statistically significant difference (p‐value 0.232).ConclusionDespite of a tendency for patients with mild cognitive impairment to have a higher risk for developing sarcopenia, it is not possible to affirm this relationship from this study, since no statistically significant association was identified.
Neighborhood Deprivation, Subjective and Objective Cognitive Impairment
Authors: Sun Britney , Yeh Fangyu , Zheng Pauline , Curtis Laura M , Yoshino‐Benavente Julia , Luu Han Q , Cecil Patrick , Agyare Prophecy , Zuleta Rodolfo , Wolf Michael S , Kim Minjee 
Published: January 2025

AbstractBackgroundSocial determinants of health have been associated with disparities in health outcomes, including cognitive impairment and Alzheimer’s disease. While individual‐level disparities have been characterized, more research is needed into structural social determinants of health (SSDoH) and their association with cognitive outcomes, especially for those in midlife. This study aimed to investigate the association between SSDoH and subjective and objective measures of cognitive impairment.MethodsEnglish‐speaking adults ages 35‐64 were recruited from an academic general internal medicine practice and federally qualified health network in the Chicagoland area. SSDoH was evaluated using the Area Deprivation Index (ADI), a validated factor‐based index of neighborhood socioeconomic context using participant census block, then divided into terciles with the highest tercile indicating highest neighborhood deprivation. Subjective cognitive concern was measured by a single question assessing concern about cognitive or memory issues as part of the Everyday Cognition Cog scales. Objective cognition was measured using the Montreal Cognitive Assessment (MoCA) with MoCA < 23 (out of 30) indicating cognitive impairment. We used univariate and multivariable logistic regression models to characterize the relationship between SSDoH and cognitive impairment, including a priori covariates of age, sex, education, and number of chronic conditions.ResultsA total of 596 participants (age 52±8; 64% female; 42% non‐Hispanic Black, 34% non‐Hispanic White, 16% Hispanic; 62% college graduate) were included in the analysis. Younger age, female sex, non‐Hispanic Black race, and lower education and income were associated with higher ADI (Table 1). One‐third of participants (34%) reported subjective cognitive concern, whereas objective cognitive impairment was found in 22.6%. Compared to the lowest ADI tercile (i.e. least deprived), the highest ADI tercile (i.e. most deprived) was significantly associated with objective cognitive impairment (aOR, 3.0; 95% CI, 1.5‐5.9; p = 0.001) but not subjective cognitive concerns (aOR, 1.2; 95% CI, 0.7‐2.0; p = 0.46), after adjusting for a priori covariates (Table 2).ConclusionsNeighborhood deprivation is associated with Future research should investigate the possible mechanisms of this association to identify optimal interventions at the neighborhood level.
Association of Cognitive Function with Mortality and Cardiovascular Risk
Authors: Melgarejo Jesus D , Charisis Sokratis , Patil Dhrumil , Vatcheva Kristina P. , Mejia‐Arango Silvia , Mena Luis Javier , Alliey‐Rodriguez Ney , Satizabal Claudia L , Chavez Carlos A , Gaona Ciro , Silva Egle , Calmon Gustavo , Lee Joseph H. , Terwilliger Joseph D. , Gutierrez Jose , Seshadri Sudha , Maestre Gladys E. 
Published: January 2025

AbstractBackgroundCognitive impairment is associated with mortality. However, evidence using population‐based studies is scarce, is limited to one cognitive assessment, and lacks the inclusion of non‐fatal adverse health outcomes. Therefore, we aimed this study to (i) investigate the association of cognitive function with mortality and cardiovascular risk and (ii) determine whether cognitive tests improve the risk‐stratification of endpoints beyond conventional risk factors.MethodsWe analyzed 946 participants aged ≥55y from a population‐based study who underwent cognitive function and were followed for fatal and nonfatal endpoints between 2001‐2016. Conventional risk factors included age, sex, education, body mass index, smoking, alcohol, antihypertensive treatment, office systolic and diastolic blood pressure, serum total cholesterol, diabetes mellitus, and previous history of cardiovascular diseases. Cognitive function examination included the mini‐mental state examination (MMSE) and selective reminder tests ([SRT], total retrieval, long‐term retrieval, and delayed recall). Our primary endpoint was total mortality and major adverse cardiovascular endpoints (MACE). Statistics included Cox proportional models and the generalized R
2 statistic to test model fit.ResultsThe mean age was 66.3±7.5 years old and 640 (67.6%) were women. During a median follow‐up of 8.5 years, 267 participants died and 187 experienced MACE. The incidence of mortality and MACE per quartiles of MMSE and SRT ranged from 13.1 (95% confidence interval [CI], 8.7‐18.9) to 23.8 (95% CI, 18.3‐30.4) among participants with the highest quartile and from 28.8 (95% CI, 14.9‐47.7) to 43.8 (26.3‐66.2) among participants with the lowest quartile. A lower MMSE score was associated with a higher risk of mortality (hazard ratios [HR] per each ‐4.3 lower MMSE, 1.23; 95% CI, 1.02‐1.48) and MACE (HR, 1.27; 95% CI, 1.09‐1.47). A lower SRT‐delayed recall score was associated with 1.19 (95% CI, 1.04‐1.37) and 1.24 (95% CI, 1.04‐1.46) higher folds of mortality and MACE endpoints. On top of conventional risk factors, the inclusions of MMSE and SRT improved the model performance (R
2 ranged from 0.51% to 1.65%; P≤0.028).ConclusionsIn this population‐based study, cognitive impairment is associated with mortality and CV risk. Given the aging global population, the assessment of cognitive function might help reduce the risk of major preventable health outcomes.
Longitudinal cortical atrophy in cases of AT concordance and discordance
Authors: Ioannou Konstantinos , Mohanty Rosaleena , Poulakis Konstantinos , Leuzy Antoine , Muehlboeck J‐Sebastian , Rodriguez‐Vieitez Elena , Westman Eric , Chiotis Konstantinos 
Published: January 2025

AbstractBackgroundAlthough β‐amyloid and tau PET positivity (A+T+) has been related to neurodegeneration and cognitive decline in Alzheimer’s disease (AD), the driving force of neurodegeneration in discordant AT cases remains controversial. We investigated the impact of AT status on longitudinal rates of cortical atrophy and cognitive decline.MethodA subset of 349 individuals (cognitively unimpaired [CU; n=230], cognitively impaired [CI; n=119]) with β‐amyloid and tau PET (a priori baseline), longitudinal MRI (interval; Mean=4.5±3.3 years, scans/individual; Median=3, IQR=[2, 8]), and a cognitive follow‐up ≥2 years, was selected from the ADNI dataset. We classified the individuals based on their AT PET status (A+; global β‐amyloid ≥20 CL, T+; composite temporal region ≥1.34 SUVR) and clustered them based on their annual rates of cognitive decline on the ADAS‐Cog13 (fast vs. slow decliners [FDs vs. SDs]). Baseline AD‐signature cortical thickness was compared across AT groups. We employed a linear mixed‐effects model to assess the interaction between AT status and longitudinal cortical thickness across all cortical regions.ResultsDemographic characteristics were similar across AT groups (A‐T‐; n=192, A‐T+; n=5, A+T‐; n=106, A+T+; n=46). Most A+T+ individuals (70%) were CI, whereas most A+T‐ (71%), A‐T+ (80%), and A‐T‐ (71%) individuals were CU. Similarly, most A+T+ individuals (85%) were characterized as FDs, whereas most A+T‐ (74%), A‐T+ (60%), and A‐T‐ (88%) individuals were characterized as SDs. A+T+ individuals showed significantly lower AD‐signature cortical thickness (MeanA+T+=2.78±0.19 mm) compared to A+T‐ (MeanA+T‐=2.89±0.15 mm; P=0.0023) and A‐T‐ (MeanA‐T‐=2.89±0.15 mm; P<0.001) individuals, and the highest Aβ burden (Mean=85.3±30.6 CL; P<0.0001) at baseline. AT status significantly influenced longitudinal cortical thickness. A+T+ individuals showed significantly steeper cortical thinning rates compared to A‐T‐ individuals, primarily in temporoparietal areas. Despite similar group‐level cortical thinning rates with A‐T‐ individuals, A+T‐ individuals showed heterogeneous patterns of cortical atrophy at the individual level. These findings remained consistent even when conducting separate analyses for CU and CI individuals.ConclusionUnlike AT discordance, concordant AT positivity exhibited homogeneous cortical atrophy patterns consistent with AD. Considering the concurrent high prevalence of mixed pathologies in neuropathological AD, we further aim to explore the underlying neurodegenerative force in discordant AT cases.
Accelerated aging elevates the risk for mortality in persons with dementia: the Age, Gene/Environment Susceptibility‐ Reykjavik Study cohort
Authors: Asefa Nigus G. , Li Zhiguang , Hu Yi‐Han , Romero Jorge M. , Meirelles Osorio , Gudnason Vilmundur , Launer Lenore J. 
Published: January 2025

AbstractBackgroundEpigenetic age acceleration (EAA) is a valuable tool for predicting all‐cause mortality and assessing disease risk. Differences in EAA reflects biologic aging (BA) and suggests underlying differences in morbidities. We examined whether EAA moderated the association of dementia to mortality risk.MethodAnalyses are based on data from the Age, Gene/Environment Susceptibility‐ Reykjavik Study (AGES‐RS) study (n = 2602, 57.5% females, mean age = 75.8 years, 30% demented). Data were collected from 2002 to 2006, with mortality data available until 2015. EAA was computed with the DunedinPACE algorithm and grouped as follows: EAA scores > 1 SD of the mean were labeled as ‘fast’, EAA < 1 SD as ‘slow’, and EAA scores within ±1 SD as ‘average’. Dementia was ascertained in a study exam or through follow‐up of health records. Cox proportional hazard analysis was used to evaluate the hazard ratio (HR, 95%CI) of mortality and the interaction between EAA and dementia. Models were adjusted for sex, chronological age, education, smoking, diabetes and stroke.ResultFast agers had higher mortality HRs than average agers (Figure 1A). Fast agers with dementia had a significantly increased risk of death (interaction p‐value = 4.08×10−2) compared to non‐demented average agers (Figure 1C); this interaction was reduced after adjusting for total brain volume (Figure 1B). Conversely, slow aging was associated with reduced mortality risk (HR = 0.71, 95% CI: 0.52‐0.98, p‐value = 3.62×10−2); however slow agers with dementia had risk estimates similar to non‐demented average agers (interaction p‐value = 1.14×10−1) but lower than demented fast agers. Controlling for total brain volume reduced the differences between slow and average agers with and without dementia.ConclusionIndividuals aging at a faster rate than their chronological age were at a higher risk for death. The rate of BA had an effect on the association between dementia and mortality. The association was partially explained by brain atrophy, suggesting other factors related to dementia contributing to mortality risk in people with dementia.
Discordance between CSF and PET biomarkers of amyloid pathology are associated with distinct pathophysiologic process in early stages of Alzheimer’s disease
Authors: An Binchong , Li Danni , Men Lu 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) pathophysiology is complex. Decrease in CSF soluble Aβ42/40 and accumulation of amyloid plaques (by amyloid PET) are two distinct biomarkers of amyloid pathology. However, the pathophysiologic process associated with each biomarker is not clear. To this end, we examined CSF protein difference across biological stages defined by biomarkers, with emphasize on early stages of AD where CSF and amyloid PET evaluations are discordant.Method392 nondemented participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were biologically defined based on CSF Aβ42, amyloid PET, and CSF p‐tau into four groups (controls [Aβ42‐/ PET‐], Stage 1a [Aβ42+/ PET‐], Stage 1b [Aβ42‐/ PET+], Stage 2 [Aβ42+/ PET+]). Of note, Abnormal CSF Aβ42(+) was defined as < 976.6 pg/mL and normal (‐) as ≥ 976.6 pg/mL; abnormal brain amyloid by PET (+) was defined as 18F‐florbetapir > 1.11 SUVR and normal (‐) as ≤ 1.11 SUVR. All 4 groups had normal CSF p‐tau (defined as ≤ 26.47 ng/mL). SomaScan was used to measure over 7000 proteins in CSF proteome.ResultThere was no significant protein difference between controls (Aβ42‐/PET‐) and Stage 1b (Aβ42‐/ PET+), or between Stage 1a (Aβ42+/ PET‐) and Stage 2 (Aβ42+/ PET+), after Benjamini‐Hochberg adjustment. We found 1462 proteins differentially expressed between controls (Aβ42‐/PET‐) and Stage 1a (Aβ42+/PET‐) related to abnormality in CSF soluble Aβ42. This number was much higher than 62 proteins differed between Stage 1b (Aβ42‐/ PET+) and Stage 1a (Aβ42+/PET‐) related to abnormality in amyloid PET. GO enrichment analysis of biological pathways and cellular components suggested neuropeptide signaling pathway and extracellular process are the most significant pathway and cellular components related to amyloid PET; whereas numerous pathways in neuron, synapse, axon were enriched and represented by protein differences related to CSF soluble Aβ42.ConclusionOur results reveal distinct pathophysiologic process associated with decrease in CSF soluble Aβ42 and increase in amyloid plaques measure by amyloid PET. Decrease in CSF Aβ42 appears to be more neurotoxic and are associated with more pathophysiological changes than increase in amyloid plaques at the early stages of AD.
Place and Space: How does the hospital environment influence the inclusion of care partners of hospitalized people living with dementia?
Authors: Still Catherine , Hoel Sydney , Strayer Andrea , Thuemling Teresa , Werner Nicole , Fields Beth 
Published: January 2025

AbstractBackgroundCare partners of hospitalized people living with dementia (PLWD) are particularly vulnerable in the hospital setting and may feel invisible during hospitalization of the PLWD they care for. Hospital initiatives for dementia friendly spaces emphasize providing a safe and supportive environment. However, literature is scarce regarding how the hospital’s physical environment influences care partners' inclusion. Therefore, we aimed to explore how the physical environment influences care partners’ inclusion in hospital‐based dementia care.MethodUsing a descriptive qualitative design and a multi‐methods approach to data collection, our team conducted direct observations in a large academic hospital’s trauma/medical surgical unit, orthopedic unit, family practice unit, and neuroscience/stroke unit. We also interviewed care partners and clinicians to gain insight into the impact the hospital environment has on the inclusion of care partners. Observational data were analyzed using a well‐known systems engineering framework, and interview data were analyzed thematically.ResultDirect observation (27 hours), care partner (15) and clinicians interviews (23) yielded insights into underutilized physical environment elements in the hospital and opportunities to enhance care partner inclusion through environmental modification. Underutilized physical environment elements included family‐designated spaces and communication tools like caregiving education bulletin boards and patient whiteboards. Care partner inclusion could be enhanced by having enough space for the care partner to be in the patient’s room comfortably, increasing opportunity to personalize spaces, and making parking more accessible.ConclusionOur findings demonstrate a need to augment the physical environment of the hospital setting. To facilitate the inclusion of care partners to PLWD, health systems must consider ways to improve their physical environment to increase care partners’ comfort and accessibility. Enhancing the physical environment of the hospital setting has potential to increase the satisfaction, health, and well‐being of both PLWD and their care partners.
Neurofilament Light and Cognition in community dwelling non‐Hispanic Blacks
Authors: Abdullah Lubnaa R 
Published: January 2025

AbstractBackgroundNo large‐scale characterizations of neurofilament light chain (NfL) and cognitive outcomes have been conducted in community dwelling non‐Hispanic Blacks.MethodBaseline data were analyzed among n = 283 non‐Hispanic Blacks (NHB) from the multi‐ethnic Health and Aging Brain Study‐ Health Disparities (HABS‐HD). Plasma NfL was measured on the Simoa platform. Linear regression models were conducted, covarying for age, gender, and education.ResultThe majority of study participants (72%) were Cognitively Unimpaired (CU), with 21 % having mild cognitive impairment (MCI), and 6.7 % with Alzheimer’s Disease (AD). In adjusted models among the entire sample, significant associations existed between NfL and Trails A (P < .0001), Trails B (p < .0001), phonemic (FAS) and semantic (Animals) fluency (p = 0.03), and Symbol Digit Substitution (p < .001). When separated by diagnostic classification, significant associations were removed for functions involving executive functions for all diagnostic groups. Higher levels of NfL were positively associated with cognitive diagnosis, older age, and less education.ConclusionPlasma NfL levels are significantly associated with measures of executive functioning, which elucidate NfL as a non‐specific marker of neurodegeneration associated with efficiency of brain functions involving attention, processing, and generativity. NfL may be a sensitive measure for the detection of alterations in cognitive processing before the onset of phenotypic functional changes of neurodegeneration.
Soluble epoxide hydrolase (sEH) is a novel anti‐inflammatory target and a first‐in‐class, picomolar sEH inhibitor (EC5026) improves cognition in a mouse model of Alzheimer’s disease
Authors: Li Yichen , Hou Yuan , McReynolds Cindy , Pieper Andrew A. , Leverenz James B , Cummings Jeffrey L. , Hammock Bruce D. , Cheng Feixiong 
Published: January 2025

AbstractBackgroundAlthough investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease‐modifying treatments for Alzheimer’s disease (AD).MethodWe performed comprehensive human genetic and multi‐omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first‐in‐class, picomolar sEH inhibitor) in a transgenic mouse model of AD‐5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons. 5xFAD mice were treated with 3 mg/kg EC5026 in drinking water for 3 months starting at 3 months of age. We evaluated the effect of EC5026 treatment on cognition using the novel object recognition test, Morris water maze and a fear conditioning test.ResultWe identified elevated sEH protein level (protein expression quantitative trait loci [pQTL] from the AD knowledge portal) is significantly associated with increased AD risk across all five large‐scale AD genome‐wide association studies (GWAS). A genome‐wide significant, protein‐coding SNP rs2741342 on EPHX2 is replicated in three pQTL datasets from the ROSMAP biobank. Further genetic and eQTL/pQTL co‐localization and fine‐mapping analyses confirmed that EPHX2 was a causal target in AD. We found that EC5026 reduced tau hyper‐phosphorylation (pTau205) in AD patient iPSC‐derived neurons. The 3 months oral administration of EC5026 significantly improved the cognition of 5xFAD transgenic mice on novel object recognition, Morris water maze and a contextual fear conditioning test. Bulk and single‐cell RNA‐sequencing analysis of EC5026‐treated brain sections revealed potential anti‐inflammatory mechanistic pathways and brain target engagement to be tested in future clinical trials.ConclusionIn summary, we demonstrate that EPHX2 (sEH) is a promising novel anti‐inflammatory target for AD and the EC5026 (a first‐in‐class, picomolar sEH inhibitor) significantly improves cognition in the 5xFAD mouse model. Future functional observations and clinical trials are warranted to validate the causal relationship of EC5026 in potential treatment of AD.