bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Cognitive Impairment in Quechua and Aymara Patients: A Critical Examination of the Rowland Universal Dementia Assessment Scale’s Discriminative Capacity
Authors: Malaga Marco , Bustamante‐Paytan Diego , Ruiz‐Yaringaño Arturo Jhonny , Custodio Belen , Soto‐Añari Marcio F. , Ore‐Gomez Maria Fernanda , Quiroz Juan Carlos Duran , Cusicanqui María Isabel , Montesinos Rosa , Custodio Nilton , Tosto Giuseppe 
Published: January 2025

AbstractBackgroundThe global aging population raises concerns about increased neurodegenerative diseases, particularly in low‐ and middle‐income countries like Latin America and the Caribbean. However, the situation among the indigenous inhabitants remains unknown due to various barriers, including cultural diversity, lack of studies, low awareness, language barriers, and limited healthcare access. Brief cognitive tests like the Rowland Universal Dementia Assessment Scale (RUDAS) show promise in overcoming these challenges.MethodA secondary analysis was conducted on a substantial patient cohort derived from the GAPP study (NIA grant #alz093273AG069118), categorizing participants based on whether their native language was Spanish or Quechua/Aymara. Descriptive analysis of variables was performed, with the Wilcoxon test applied to compare total RUDAS scores among distinct patient groups, including controls, individuals with Mild Cognitive Impairment (MCI), and those with dementia. Comparisons were specifically made between Spanish speakers and native language speakers. Additionally, the ROC (Receiver Operating Characteristic) curve was employed to evaluate the discriminative capacity of RUDAS in distinguishing between controls and dementia, as well as between controls/MCI and dementia cases within native and Spanish‐speaking populations.ResultA total of 405 controls, 126 individuals with Mild Cognitive Impairment (MCI), and 133 participants with dementia were included in the analysis. Among them, 91 patients were native language speakers, with a median age of 74 (range 54 ‐ 92). The majority were female (69.2%), and 65.9% were Aymara speakers. Native participants reported an average education level of 3.1 years (SD 4.4). The RUDAS mean score was lower in the native speaker group compared to Spanish‐speaking participants (21 vs. 23). Additionally, the analysis revealed significantly lower scores in controls within the native speaker group (Fig. 1). Diagnostic performance for native speakers was poor when comparing control/MCI (Fig. 2) vs. dementia and control vs. dementia (Fig. 3).ConclusionThe use of the RUDAS in native language speakers and its ability to distinguish between Mild Cognitive Impairment (MCI) and dementia raise some concerns. To improve assessments for various communities in Latin America and the Caribbean, there is a need for culturally adapted brief cognitive tests.
Reducing the effects of aging on cognition with therapeutic intervention of an oral multi‐nutrient combination (REACTION): A pilot study – Report of primary feasibility outcomes and quality of unblinding
Authors: Camargo Christian J , McInerney Katalina F , Merritt Stacy S , Modjeski Marisa , Rundek Tatjana 
Published: January 2025

AbstractBackgroundAge‐related cognitive decline (ARCD) refers to the cognitive changes that occur in individuals because of aging. Research suggests that the underlying mechanism behind ARCD is a loss of synaptic plasticity and altered dendritic spine morphology. Similarly, the cognitive changes in Alzheimer’s Disease (AD) are also thought to arise from impaired synaptic plasticity and dendritic spine loss. A specific combination of precursors and cofactors for phospholipid biosynthesis has shown beneficial effects on memory, cognition, and brain atrophy in prodromal AD. To test the feasibility of this multi‐nutrient combination intervention in ARCD, the REACTION pilot study was developed.MethodREACTION is a 6‐month single‐center randomized, double‐blind, placebo‐controlled parallel group virtual pilot clinical trial. The study factors in local COVID‐19 restrictions and trial visits are done virtually using secure online video communication. Eligible subjects are English or Spanish speaking people aged 55−89 years from all ethnic groups with ARCD and screened and randomized to the oral multi‐nutrient combination (Souvenaid) or placebo on a 1:1 basis. The main outcome is feasibility (recruitment rate, recruitment time, adherence rate and retention rate). Exploratory outcomes include memory (e.g., Ray Verbal Learning Task), performance on other cognitive tasks (e.g., Oral Trail Making Test), and quality of life (e.g., Amsterdam IADL Questionnaire) outcome measures.ResultIn JPAD (Camargo et al., JPAD. 2023;10:821‐7), we published our final pre‐specified criteria for feasibility. We report that we met pre‐specified criteria for “feasible” for recruitment rate, recruitment time, and study retention. We are unable to draw conclusive data on adherence to intervention due to staff shortages for data acquisition. After unblinding, for the placebo‐controlled portion of the study, we report that our randomization was successful, e.g., with matched age (69.8 years ± 9.12 [STD] and 68.5 years ± 8.67 [STD], p = N.S.), years of education (17.3 ± 2.38 [STD] and 16.69 ± 2.36 [STD], p = N.S.) for placebo and active groups, respectively. This will enable exploratory analysis of efficacy outcomes of cognitive and behavioral data.ConclusionThis study shows that conducting a fully virtual study with a nutritional intervention to test its effect on ARCD progression is feasible in persons with ARCD.
Synergism between Lewy body and Alzheimer’s disease pathology differs by sex
Authors: Alexander Madeline Wood , Barnes Lisa L. , Schneider Julie A. , Casaletto Kaitlin B. , Rabin Jennifer S 
Published: January 2025

AbstractBackgroundParkinson’s disease and dementia with Lewy bodies are more common in men, while Alzheimer’s disease (AD) is more common in women. Lewy body disease (LBD) and AD pathologies are highly comorbid and may be mechanistically linked. It remains unclear whether LBD and AD co‐pathology manifest differently across sexes. Here, we investigated sex differences in associations of LBD with β‐amyloid and tau. We also tested whether age at menopause modifies the relationship between LBD and AD pathology in women.MethodWe used data from autopsied participants in the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study cohorts. Immunohistochemistry was used to quantify LBD stage, β‐amyloid, and tau. To capture cortical LBD pathology, LBD stage was dichotomized as neocortical‐type/limbic‐type vs. nigral‐predominant/none. Linear regressions tested interactive effects of 1) sex and LBD on AD pathology in the entire sample and 2) age at menopause and LBD on AD pathology among female participants who reported natural menopause, adjusting for age at death and APOE4.ResultsWe included N = 1,798 participants (mean (SD) age at death = 89.5 (6.74) years, N (%) female = 1,225 (68.1)). Between sexes, men exhibited more LBD pathology after adjusting for β‐amyloid and tau (β = 0.31, p = .02), while women showed a greater burden of both β‐amyloid (β = ‐0.10, p = .002) and tau (β = ‐0.08, p = .01) after adjusting for LBD. There was an interaction between sex and LBD on tau but not β‐amyloid, such that women with LBD had more tau than men with LBD after adjusting for β‐amyloid (male sex*β‐amyloid: β = 0.03, p = .7; male sex*tau: β = ‐0.16, p = .03; Figure 1). In women with natural menopause, age at menopause modified the association of LBD with tau, such that women with earlier menopause had greater tau burden in the presence of LBD (β = ‐0.03, p = .003; Figure 2). Post hoc analyses showed that the interactions between 1) sex and LBD on tau and 2) age at menopause and LBD on tau were driven mainly by neocortical‐type LBD and not limbic‐type LBD.ConclusionLBD pathology might have a more pronounced impact on tau vulnerability in women than men. Female hormonal processes may further modify the relationship between LBD pathology and tau.
Cognitive trajectory patterns in oldest‐old individuals for identifying SuperAgers: The Life After 90 Study
Authors: Biswas Roshni , Jiang Luohua , Kawas Claudia H. , Gilsanz Paola , Whitmer Rachel A. , Corrada María M. M. 
Published: January 2025

AbstractBackgroundOldest‐old individuals exhibit heterogeneous cognitive function ranging from superior cognitive performance to dementia. Most SuperAger definitions rely on cross‐sectional memory scores. Here, we extend the definition by identifying distinct subgroups based on longitudinal trajectories for memory. We also evaluated longitudinal trajectories for executive function.MethodThe 774 study participants were from the LifeAfter90 study (LA90), a multi‐ethnic cohort of individuals aged 90 or older. Verbal episodic memory (VEM) and executive function (EF) were assessed approximately every 6 months using the Spanish and English Neuropsychological Assessment Scale from at least two visits (mean = 4; range: 2‐7). Using group‐based trajectory modelling, we identified unique trajectories separately for VEM and EF, accounting for baseline age, sex, education, and race/ethnicity.Result62% of participants were women, the overall mean baseline age was 92.4 (±2.3), and 26% had ≤high school education (Table 1). We identified four distinct trajectories for VEM (Figure 1). Group 4‐High stable performers: with the highest baseline performance, largest practice effects, and no decline; Group 3‐Stable performers: with a lower baseline than group 4, moderate practice effects, and slight decline; Group 2‐Slow decliners: with lower baseline than groups 4 and 3, slight practice effects, and a slow declining trajectory; and Group 1‐Accelerated decliners: with the lowest baseline performance, no practice effects, and rapid decline. Thus, we identified one subgroup with no decline in longitudinal performance and with practice effects that could be classified as SuperAgers. For EF, we also identified four groups (Figure 2). Baseline EF scores varied for Groups 4, 2, and 1 (Group 4 being the highest) and followed relatively stable trajectories. Group 3, which had the second highest baseline score, had a slowly declining trajectory. For EF, stable trajectories were not limited to the top baseline performing groups. The two domains had distinct patterns with limited overlap in group memberships.ConclusionUsing longitudinal patterns, we identified SuperAgers based on superior memory performance and no decline. In future research, we will further explore the use of longitudinal performance trajectories and the use of multiple cognitive domains in the definition of SuperAgers. We will also identify defining characteristics of each subgroup.
Exploring the differential impact of sociodemographic and extrinsic factors on mobility‐based digital phenotypes versus standard cognitive tests among older adults
Authors: Hackett Katherine , Xu Shiyun , McKniff Moira , Barnett Ian , Giovannetti Tania 
Published: January 2025

AbstractBackgroundPassively‐obtained smartphone digital phenotypes may yield objective estimates of everyday cognition in older adults compared to traditional cognitive/self‐report measures typically confounded by sociodemographics. However, it is currently unknown what covariates are relevant when interpreting smartphone sensor data. We aimed to clarify which intrinsic and extrinsic factors are associated with digital phenotyping versus traditional cognitive measures in a cohort of older adults.Methods34 participants (Mage = 71.6±5.5; Meducation = 16.4±2.7; 57% non‐Hispanic White; 88% native English language) with normal cognition or Mild Cognitive Impairment used an open‐source smartphone application (mindLAMP) to passively capture GPS trajectories for one month. Baseline neuropsychological tests were collected as external validators along with self‐reported sociodemographics (intrinsic) and technology habits/phone type (extrinsic). GPS data were processed into monthly feature estimates of activity, routine, and location diversity. Correlations and univariate ANOVAs were used to examine relationships between GPS features, z‐transformed neuropsychological tests, and intrinsic/extrinsic factors.ResultsConsistent with prior findings, greater monthly GPS activity (radius of gyration), less routine (physical circadian routine), and more location diversity (significant locations visited) associated with higher scores on measures of attention, executive functioning, and language (.36≤|r’s|≤.50, p’s<.05). Several sociodemographic factors associated with cognitive scores but not with GPS features; these included age, education, living alone (.34≤|r’s|≤.47, p’s<.05) and race (3.8≤F(2,30)≤ 5.5, .20<η2<.27, p’s<.05). Higher lifetime income and native English language associated with better cognitive scores and with more GPS activity/less routine (.35≤|
r’s|≤.57, p’s<.05). Sex and current occupational status were not associated with cognitive tests or GPS features. iPhone vs. Android ownership associated with cognitive tests but not GPS metrics (.35≤r’s≤.37, p’s<.05), whereas more habitual smartphone use associated with less location diversity but not with other GPS metrics or cognitive tests (r = ‐.40, p<.05).ConclusionsPassively‐obtained mobility phenotypes were significantly and moderately correlated with gold standard neuropsychological tests commonly used for clinical assessment and clinical trial endpoints. Several factors pertinent to social determinants of health were related to neuropsychological tests but not GPS features, suggesting naturalistic assessment via digital phenotyping may be less biased by these factors. On the other hand, other important factors including lifetime income and native English language impacted both methods of assessment.
Comparing the utility of mean versus intraindividual variability metrics in the relationship between mobility‐based digital phenotypes and cognition
Authors: Hackett Katherine , Xu Shiyun , McKniff Moira , Barnett Ian , Giovannetti Tania 
Published: January 2025

AbstractBackgroundIntraindividual variability (IIV) on neuropsychological task performance has demonstrated enhanced sensitivity to neuropathological decline compared to mean performance. It is currently unknown whether increased IIV in everyday behaviors may also lend added sensitivity to detect early subtle changes seen in pre‐clinical ADRD.MethodsIn a pilot smartphone digital phenotyping study, 34 participants (Mage = 71.6±5.5; Meducation = 16.4±2.7; 68% female 57% non‐Hispanic White) with healthy cognition or Mild Cognitive Impairment downloaded an open‐source smartphone application (mindLAMP) to passively capture GPS trajectories for 4 weeks. Monthly mean and day‐to‐day standard deviation (IIV) metrics for three GPS features were generated to test a priori hypotheses based on a conceptual framework. Correlations examined the relationship between mean versus IIV mobility metrics and 11 baseline neuropsychological T‐scores adjusted for age, sex, education, and estimated premorbid IQ. Hierarchical linear regressions examined whether mobility IIV was independently associated with cognition after adjusting for mean mobility, and vice versa, for relationships in which both mean and IIV were significantly correlated with the same cognitive outcome.ResultsGreater mean GPS activity (radius of gyration), less mean GPS routine (physical circadian routine), and greater IIV in these two GPS features were both significantly associated with a neuropsychological measure of language (Boston Naming Test; .39≤|r’s|≤.55, p’s<.05). IIV in GPS routine did not explain a significant amount of additional variance in Boston Naming scores after controlling for mean GPS routine, whereas mean routine explained an additional 11% of variance after controlling for IIV (Overall model: R2 = .34, F(2,31) = 8.07, p = .002). Unique associations were identified between IIV in GPS routine and animal fluency scores (r = .44, p<.05) and IIV in GPS location diversity and Boston Naming (r = .35, p<.05), whereas mean metrics of these features were not associated with corresponding outcomes.ConclusionsMobility‐based digital phenotyping features appear to be selectively associated with demographically‐corrected neuropsychological measures of language. Considering IIV in everyday mobility behaviors – in addition to overall mean mobility features ‐ may lend added value. Next steps will evaluate and compare a greater array of digital phenotyping features (mean and IIV) in predicting cognition and other relevant outcomes.
Interaction between polymorphisms in MBP and EIF2B5 genes is significantly associated with Alzheimer’s disease
Authors: Yashin Anatoliy I , Wu Deqing , Arbeev Konstantin , Duan Hongzhe , Holmes Rachel , Bagley Olivia , Ukraintseva Svetlana 
Published: January 2025

AbstractBackgroundResults of recent analyses indicate that axon demyelination may play an important role in AD pathology. The MBP gene encodes a myelin basic protein involved in axon myelination in the nervous system including the central nervous system. Polymorphisms in this gene, as well as variations in expression, have been associated with multiple sclerosis (MS). Evidence of the involvement of this gene in Alzheimer’s disease (AD) is emerging. The EIF2B5 gene codes for a subunit of eukaryotic translation initiation factor 2B (eIF2B), a master regulator of translation. Recent studies connected EIF2B5 and its polymorphisms with various health disorders including MS and AD, as well as hypomyelination. The latter was also associated with reduced MBP. Considering this, and that both MBP and EIF2B5 have been associated with AD, we hypothesized that the interplay between these two genes might also be associated with AD.MethodsTo test this hypothesis, we analyzed data on genotyped individuals (males and females combined) from the Health and Retirement Study using a logistic regression model with the interaction term. Education, smoking status, sex, and the first five principal components were included as observed covariates. The binary AD trait was defined as “0” if AD onset was observed at any age, and as “1” if a person survived to age 85 and did not get AD during their life. Linkage disequilibrium (LD) test and SNP‐clumping procedures were used to reduce the number of tests in SNPxSNP interaction analysis and make Bonferroni correction less conservative.ResultsWe found a statistically significant positive association of the interaction between intronic rs12959006 in MBP gene and missense variant rs843358 in the EIF2B5 gene with AD. The rs12959006 was associated with MS and rs843358 in survival from cancer in the literature. Several other SNPs that are in high LD with the SNPs found in this study have also been separately associated with health traits in the literature.ConclusionThe results of this study support the hypothesis that the interaction between MBP and EIF2B5 variants is significantly associated with AD. Our finding implies that regulation of translation and axon demyelination jointly contribute to AD.
Investigating the microvascular dysfunction in the Frontotemporal Dementia using a progranulin‐deficient mice model
Authors: Chakraborty Supriya , Franciosa Sofia , Bracko Oliver 
Published: January 2025

AbstractBackgroundDespite being the second most common form of dementia, vascular contributions of Frontotemporal Dementia are understudied. Recent data from patients and preliminary experiments have indicated that in progranulin‐deficient mice, an increased number of cortical capillaries are stalled, and cerebral blood flow is reduced. Here, we examined the underlying mechanism contributing to microvascular dysfunction in FTD.MethodBlood‐brain barrier (BBB) integrity was examined using immunohistochemistry and protein analyses. We compared PGRN‐deficient mice to controls and tested for the tight junction proteins Claudin‐5, Occludin, and markers of BBB leakage, such as Albumin. High Resolution in vivo two‐photon Imaging was utilized to detect the capillary stalls and capillary blood flow in the cortical capillaries, and the images were analyzed using MATLAB and ImageJ software.ResultWe discovered that the number of blood vessels significantly decreased in the 10‐11 month‐old PGRN‐deficient mice compared to controls. Furthermore, the tight junction protein levels of Claudin‐5 and Occludin are significantly reduced in PGRN‐deficient mice compared to age and sex‐matched controls. Finally, in‐vivo multiphoton experiments revealed a reduction in cerebral blood flow associated with a increased number of capillary stalling.ConclusionThis study shows that the BBB is damaged in PGRN‐deficient mice, accompanied by microvascular dysfunction and hypoperfusion. The data suggest that PGRN‐deficient mice could be an ideal model to investigate vascular contributions to FTD.
Early menopause and cognitive impairment: Insights from the ELSI‐Brazil Study
Authors: Franco Alvaro de Oliveira , Leotti Vanessa Bielenfeldt , Zimmer Eduardo R. , Castilhos Raphael Machado 
Published: January 2025

AbstractBackgroundDementia and cognitive impairment, primarily linked to aging, are increasingly recognized as multifactorial conditions. Emerging research has pointed to early menopause as another potential risk factor. However, its relationship with cognitive impairment needs further investigation, especially in low‐ and middle‐income countries. Therefore, this study aims to analyze the effect of early menopause on cognitive impairment in the Brazilian population.MethodsWe analyzed data from the Brazilian Longitudinal Study of Aging (ELSI‐Brazil), a nationally representative study of individuals older than 50 years. In this analysis, we included only women (n = 4,494) and defined early menopause as when its age of onset occurred before 45 years. A Global Cognitive Score (GCS) was computed by standardizing Z scores yielded by the assessment of four cognitive subdomains (orientation, fluency, episodic memory, and semantic memory). Depression was assessed using the Epidemiological Scale‐Depression 8 (CES‐D8), with scores of 3 or higher indicating depression. High cardiovascular risk (HCR) was defined by a history of stroke or heart attack. We conducted a general linear model with GCS as the dependent variable, and early menopause, age, HCR, and depression as covariates. Statistical analyses were performed in the R environment, and significance was set at p < 0.05.ResultsOf the 4,494 women included in the study, 1,218 (27.1%) had early menopause. Age between groups is not different, but the group with early menopause had fewer years of education than women with normal menopause (p < 0.001) (Table 1). Early menopause is significantly and independently associated with lower scores in GCS (β: ‐0.112, p <0.001), implying a lower performance in the cognitive assessment. Seemingly, depression (p < 0.001), age (p < 0.001), and high cardiovascular risk (p = 0.009) negatively impact GCS.ConclusionsOur study shows early menopause as an independent factor associated with cognitive impairment in a representative sample of the Brazilian population. Further research is warranted to elucidate the underlying mechanisms linking early menopause to cognitive impairment and to develop effective interventions that can optimize cognitive health in this vulnerable population.