bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visceral adipose tissue triggers tau pathogenesis in transgenic mice
Authors: Bettinetti‐Luque Miriam , Trujillo‐Estrada Laura , Andreo‐Lopez Juana , Cantero‐Molina Francisco , Da Cunha Celia , Sanchez‐Mejias Elisabeth , LaFerla Frank , Gutierrez Antonia , Baglietto‐Vargas David 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex disorder and multiple cellular and molecular mechanisms are involved in AD onset and progression. Recent evidences have suggested that metabolic alterations are an important pathological feature in disease progression in AD. Likewise, diabetes and obesity, two mayor metabolic illnesses, are risk factors for AD. These two overwhelming diseases are associated with a significant expansion of visceral adipose tissue. Here, we hypothesize that the visceral adipose tissue may serve as a key communicator organ between the brain and peripheral metabolic illnesses and affecting both types of disorders.MethodWe used histological stains, immunohistochemistry and biochemical means to determine changes in the visceral adipose tissue from WT and db/db mice. Moreover, similar techniques were used in 3xTg‐AD mice that received white fat pads from WT and db/db donors to determine any changes in amyloid and tau pathology.ResultOur study shows that recipient 3xTg‐AD mice from db/db fat pads mice develop profound changes in tau pathology due to increased CDK5 expression compared to 3xTg‐AD mice that received fad pads from WT mice. This increment in tau level was associated with elevated levels in IL‐1β and profound microglia activation. Moreover, we found the opposite effect on amyloid pathology, in which insoluble Aβ levels and Thioflavin positive plaques were reduced in recipient 3xTg‐AD mice from db/db fat pads compared to 3xTg‐AD mice that received fad pads from WT mice. These reduction in Aβ levels were correlated with an increment in microglia phagocytic capacity.ConclusionOverall, our study demonstrate a novel important crosstalk between Alzheimer´s disease and obesity/diabetes type II through visceral adipose cells and a differential effect on tau and Aβ pathology mediated by an activated immune response.This study was supported by Minister of Science and Innovation grant PID2019‐108911RA‐100 (D.B.V.), Alzheimer’s Association grant AARG‐22‐9282/9, Beatriz Galindo program BAGAL18/00052 (D.B.V.), University of Malaga grant PPIT.UMA.B1‐2021_32(LTE) and Institute of Health Carlos III (ISCiii) grant PI18/01557 (A.G.) co‐financed by FEDER funds from European Union.
Association between monolinguals, multilinguals and cognition
Authors: Menon Anjana J , Issac Thomas Gregor , Sundarakumar Jonas S. , Stezin Albert , Malo Palash Kumar , Arvind Prathima , Mallikarjun Divya N , Hameed Shafeeq K Shahul , Lingegodwa Abhishek Mensegere , Narayanasamy Rajitha , Menon Meenakshi , Rai Pooja , Singh Sadhana , Velavarajan Goutham , Partha Ajith , M Amitha C , R Meghana 
Published: December 2023

AbstractBackgroundRecent research suggests that multilingualism may play an important role in enhancing cognitive health. The process of language acquisition constitutes a form of natural brain training, which in turn is thought to increase the neuroplasticity. The aim of this study is to examine the association between multilingualism and cognitive performance.MethodThis study utilized cross‐sectional (baseline) data from the Srinivasapura Aging Neuro Senescence and COGnition study (SANSCOG), which is an ongoing community‐based, longitudinal aging cohort study conducted in a rural setting in Southern India. Study participants were dementia‐free, aging adults (45 years and above) from the villages of Srinivaspura. This study site is located in the state of Karnataka, close to the border of an adjoining state, Andhra Pradesh. The subjects are separated into two groups, namely monolinguals, participants knowing one language and multilinguals, participants knowing more than one language, to assess if language has any role in cognitive performance. The cognitive performance of the participants was assessed using Hindi Mental State Examination (HMSE) and Clinical Dementia Rating (CDR). A total of 3283 subjects for HMSE, and 3634 for CDR, including both normal and cognitively impaired subjects were considered for the study. Dementia free patients with HMSE scores below 24 and CDR scores of 0.5 are considered as the inclusion criteria. The data analysis was performed using chi‐square test.ResultThe study showed a statistical significance for the association between number of languages spoken and cognition. Multilinguals achieved better cognitive scores, which shows their greater flexibility in cognition. The p value and chi‐square (p value:< 0.001; chi‐square: 59.448) of monolinguals and HMSE scores shows that the analysed data is significant. The odds ratio is 2.562 and it indicates that monolinguals have higher odds of developing cognitive decline than multilinguals. The analysis indicates that exposure to multiple languages has the upper hand, as it is thought to enhance the brain function.ConclusionThis study highlights that learning multiple languages might have a profound impact on cognitive health, thereby reducing the likelihood of developing cognitive impairment.
Comparison of Executive Functioning between Ageing Urban and Rural Participants in India: A Cross‐sectional Analysis
Authors: Menon Meenakshi , Lingegodwa Abhishek Mensegere , Stezin Albert , Hameed Shafeeq K Shahul , Malo Palash Kumar , Narayanasamy Rajitha , R Meghana , Mallikarjun Divya N , Partha Ajith , M Amitha C , HS Sunitha , Velavarajan Goutham , Singh Sadhana , Diwakar Latha , Kommaddi Reddy Peera , Sundarakumar Jonas S. , Issac Thomas Gregor 
Published: December 2023

AbstractBackgroundOlder adults living in urban areas differ from their rural counterparts in many ways, including the cognitive performance. Executive functioning is one of the few cognitive domains that is implicated to be affected in early stages of dementia. However, there are very few studies that have explored differences in cognitive functioning across rural and urban contexts in India. Our objective was to evaluate differences in executive functioning across urban and rural participants.MethodOur study sample includes ageing individuals (≥ 45 years): 1089 from the urban Tata Longitudinal Study on Ageing (TLSA) cohort and 4913 from the rural Srinivaspura Ageing, Neuro Senescence and COGnition (SANSCOG) study cohort. The TLSA and SANSCOG are parallel, harmonised, community‐based cohort studies in urban and rural India exploring the risk and protective factors associated with cognitive changes due to normal ageing, dementia and other related disorders. The difference in executive functioning measured by Categorical fluency, Letter fluency, Visuospatial span and Stroop tests were compared across both cohorts.ResultUrban participants were older, had more years of education had less Geriatric Depression Score (GDS) as shown in Table 1. They did not differ in gender and proportion of cognitive impairment. Multiple Linear Regression analysis was performed to examine the effects of each executive functioning tests between both the cohorts (urban participants were coded as reference category) while age, years of education and GDS were adjusted.Urban participants performed better than Rural participants on Categorical fluency (β = ‐2.379, p < 0.001), Letter fluency (β = ‐4.343, < 0.001), Visuospatial span (β = ‐0.279, < 0.001) and Stroop (β = 0.934, < 0.001). Similar results were obtained after gender stratification as shown in Table 2.ConclusionUrban participants performed better than their rural counterparts in all tests examining executive functioning. Poorer cognitive functioning in the rural ageing cohort could be due to a number of reasons including limited or less cognitively demanding occupations. There is a need for more such longitudinal studies in India that explore community environment on cognitive function across different cohorts.
LatAm‐FINGERS and U.S. POINTER: Design and Cohort Characteristics of Parallel Harmonized Trials of Multidomain Lifestyle Interventions Targeting Cognition
Authors: Suemoto Claudia Kimie , Allegri Ricardo Francisco , Baker Laura D , Brucki Sonia Maria Dozzi , Crivelli Lucía , Calandri Ismael Luis , Caramelli Paulo , Carrillo Maria C. , Cleveland Maryjo , Farias Sarah Tomaszewski , Gitelman Darren R. , Kivipelto Miia , Lopera Francisco , Nitrini Ricardo , Pavlik Valory , Salinas‐Contreras Rosa Maria , Salloway Stephen , Sevlever Gustavo , Snyder Heather M , Sosa‐Ortiz Ana Luisa , Tangney Christy C , Vellila Lin , Whitmer Rachel A. , Wing Rena R. , Yassuda Monica Sanches , Yu Melissa , Espeland Mark A. ,   LatAm FINGERS Consortium and U.S. POINTER Study Group
Published: December 2023

AbstractBackgroundMultidomain lifestyle interventions hold great promise world‐wide as interventions to slow cognitive aging, and delay and prevent Alzheimer’s Disease and Related Disorders (ADRD). To have the greatest reach, they must be tailored for and assessed within local cultures in clinical trials. For trials to have the greatest impact, it’s important that they are designed with common features that promote comparisons and potential harmonization.MethodWorld‐Wide FINGERS was launched in 2017 as a global network of multidomain lifestyle intervention trials to adapt, test, and optimize multidomain lifestyle intervention trials in regions worldwide. Two participating trials, the Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm‐FINGERS) and the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) have collaborated to promote harmonization to support joint initiatives. This presentation is organized to describe, in parallel, their study protocols, and cohort characteristics, and demonstrate how cross‐trial collaboration may expand the impact of individual trials.ResultThe trials have overlapping aims, eligibility criteria, interventions, and assessment protocols. LatAm‐FINGERS and U.S. POINTER will enroll 1,200 and 2,000 participants, respectively. Table 1 describes sample characteristics. The samples of the two studies share similar sociodemographic and clinical characteristics with a few exceptions. In U.S. POINTER, there is a larger proportion of participants with a family history of memory impairment and physical inactivity, and a higher frequency of White participants. Additionally, mild memory impairment (Clinical Dementia Rating = 0.5) is more common in LatAm‐FINGERS participants.ConclusionHarmonization of LatAm‐FINGERS and U.S. POINTER protocols provides unique opportunities for collaborative science for identifying effective strategies to promote cognitive resilience and reduce risks for Alzheimer’s disease, and significantly expand the potential for scientific investigation in diverse populations.
Colocalization of tau PET uptake and cerebral blood flow alterations within subjects with MCI and AD
Authors: Scott David , Bracoud Luc , Conklin Chris , Ingalhalikar Madhura , Suhy Joyce 
Published: December 2023

AbstractBackgroundThe accumulation of neurofibrillary tangles contributes to a neurodegenerative cascade toward Alzheimer’s disease, of which altered cerebral metabolism is also a feature. 18F‐Flortaucipir PET allows visualization of tau pathology in vivo, while MRI‐based arterial spin labeling techniques assess metabolism via cerebral blood flow. We sought to characterize the within‐subject relationship between tau burden and cerebral blood flow throughout the brain.Method130 ADNI3 subject visits with concurrent MRI ASL and flortaucipir PET scans were selected from the database (http://adni.loni.ucla.edu) for analysis. ADNI PET core PVC values referencing inferior cerebellar cortex were used to index SUVR across the entire FreeSurfer parcellation, and ADNI MRI core regional CBF values were identified from an overlapping set of 71 FreeSurfer regions. Linear partial correlation coefficients were calculated for tau PET SUVR and CBF in each brain region, controlling for age and amyloid PET SUVR. Lasso logistic regression returned penalized maximum‐likelihood fitted coefficients for a generalized linear model estimating meta‐temporal tau SUVR from regional CBF; regions with non‐zero coefficients in the sparsest model are reported.ResultFollowing correction for age and amyloid load, significant within‐subject partial correlations between tau PET uptake and ASL CBF were observed throughout the brain. The associations were strongest in amyloid positive subjects with MCI or AD. Correlation strength was regionally specific and strongly positive (marginal p < 0.005) in subcortical and early Braak regions, while strongly negative (marginal p < 0.005) across frontal and later Braak regions. The strongest tau burden associations were observed with hypermetabolism in hippocampus (p = 0.0005, partial r = 0.59), and hypometabolism in posterior cingulate gyrus (p = 0.0001, partial r = ‐0.63). Lasso regression revealed a subset of non‐zero coefficients in the sparsest model including subcortical, temporal, parietal and frontal brain regions.ConclusionTau PET uptake is associated with a pattern of hypermetabolism in early Braak stages, and hypometabolism in later Braak stages. This suggests a dynamic relationship where tau accumulation and cerebral blood flow alterations colocalize, but the direction of the effect is regionally specific.
NG‐001: A novel multi‐domain digital cognitive intervention for cognitive symptoms in mild cognitive impairment
Authors: Patterson Michael D. , Ng Kok Pin , Jabar Syaheed Bin , Leonardo Jacklyn , Chiew Hui Jin , Ng Adeline Su Lyn , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) is a prodromal stage of Alzheimer’s disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain intervention to improve cognitive performance. Therefore, we aim to investigate the utility of a novel, scalable multi‐domain digital intervention as a therapeutic solution to prevent or reverse cognitive decline.Method30 amnestic MCI patients were enrolled in a pilot open‐label clinical trial of a 10‐week digital therapeutic intervention using NG‐001 delivered via a tablet. 27 participants completed the trial and their data were analyzed. NG‐001 consisted of weekly 1‐hour trainings spread across several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. The outcome composite scores were calculated from the Neuropsychological Test Battery including Overall Cognition, Processing Speed, Executive Functioning, Overall Memory as well as Immediate and Delayed Memory. Composites were calculated into Z‐scores based on normative data from age and education‐adjusted reference groups. Changes in the Z‐scores were then assessed using paired Wilcoxon signed ranked tests (two‐tailed) and the effect size was calculated using Hedges’ g.ResultCompared to baseline, at post‐intervention, MCI patients showed significant improvements in Overall Cognition (‐0.440 to ‐0.213, g = 0.352), Overall Memory (‐0.587 to ‐0.132, g = 0.407), Immediate Memory (‐0.549 to ‐0.030, g = 0.512) and Delayed Memory (‐0.626 to ‐0.233, g = 0.305). There were no significant changes in Processing Speed or in Executive Functioning (ps > .05).ConclusionNG‐001 significantly improved memory (both immediate and delayed) for amnestic MCI patients, indicating its potential as a form of digital therapeutics for early intervention of memory impairment in MCI. Further research is needed to investigate the mechanisms involved in this improvement, and whether modifications can be made to extend its facilitatory effect to other cognitive domains such as executive functioning and language.
Characterizing the Retinal and Choroidal Microvasculature and Structure in Individuals with Dementia with Lewy Bodies
Authors: Joseph Suzanna , Allen Ariana , Haystead Alice , Kundu Anita , Hemesath Angela , Robbins Cason B , Ma Justin , Johnson Kim G , Stinnett Sandra , Grewal Dilraj S , Fekrat Sharon ,   iMIND Study Group, Duke University School of Medicine
Published: December 2023

AbstractBackgroundDementia with Lewy Bodies (DLB) accounts for about 7% of dementia cases. Multimodal retinal imaging may identify biomarkers in this population since there is a growing link between retinal alterations in DLB, with exploratory studies showing phosphorylated alpha‐synuclein retinal deposits, parafoveal thinning of ganglion cell inner‐plexiform layer (GC‐IPL), and electroretinography alterations (Beach et al., 2014, Murueta‐Goyena et al., 2019, Maurage et al., 2003). We used optical coherence tomography (OCT) and OCT angiography (OCTA) to characterize differences in retinal and choroidal microvasculature and structure in individuals with DLB compared to controls with normal cognition.MethodA cross‐sectional comparison of patients with DLB and age‐ and sex‐matched cognitively normal controls. Exclusion criteria included retinal or optic nerve pathology, glaucoma, and diabetes. The Zeiss Cirrus HD‐5000 with AngioPlex was used to obtain OCT and OCTA images. OCT parameters measured includes central subfield thickness (CST), retinal nerve fiber layer (RNFL) thickness, GC‐IPL thickness, and choroidal vascularity index (CVI). OCTA parameters measured include superficial capillary plexus foveal avascular zone (FAZ) area, fovea‐centered 3×3mm and 6×6mm vessel density (VD) and perfusion density (PD), and optic nerve head‐centered capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equations adjusted for correlation among eyes of the same subject.ResultThirty‐four eyes of 18 DLB patients and 85 eyes of 48 cognitively normal controls were analyzed. Cases were well‐matched to controls by age (p = 0.977) and sex (p = 0.607). DLB patients had lower Mini Mental State Exam (MMSE) scores (p < 0.001). Average GC‐IPL thickness was lower in patients with DLB compared to controls (p = 0.04). Average 4.5×4.5mm CPD was higher in patients with DLB compared to controls (p = 0.005). Average 4.5×4.5mm CFI was lower in patients with DLB compared to controls (p = 0.016).ConclusionDLB patients had attenuated GC‐IPL thickness and peripapillary CPD and CFI changes when compared to those with normal cognition. Retinal imaging metrics have the potential to serve as clinically relevant biomarkers for DLB diagnosis.
Scalable Multi‐Sensor At Home Assessment of Sleep and Activity in Adults At High Risk for Dementia
Authors: Lim Andrew , Centen Andrew Peter , Montazeri Nasim , Gibson Erin , Dang‐Vu Thien Thanh , Carrier Julie , Chan Senny , Belleville Sylvie , Nygaard Haakon B. , Montero‐Odasso Manuel , Feldman Howard H. , Chertkow Howard ,   CCNA‐CAN‐THUMBS‐UP Study Group
Published: December 2023

AbstractBackgroundSleep disruption is common in older adults, and emerging evidence suggests that differences in sleep whether measured by electroencephalography (EEG) or actigraphy, may be associated with clinical cognitive outcomes, and with specific dementia‐associated pathologies. However, whether EEG and actigraphic sleep features may predict cognitive response to lifestyle interventions for dementia, or whether they may themselves respond to these lifestyle interventions, is unknown. A major challenge is to develop sleep assessment in virtual studies where subjects do not attend a research center.MethodsIn the Canada‐wide Brain Health Support Program (BHSP), 350 adults at high risk for dementia have been recruited to receive an online lifestyle risk factors intervention. At baseline, and at 12‐month follow‐up, we are assessing 3 nights of sleep EEG and 10‐days of wrist accelerometry at home using a mailed‐out package. Wearable devices are mailed to subjects, who are instructed in their use, and data is collected remotely. The wearables are then mailed back to the study center. We used the MUSE‐S (Interaxon, Toronto, Canada), which is a multimodal wearable headband combining 4‐channel dry‐electrode EEG, with accelerometry and photoplethysmography, along with the AX3 wrist triaxial accelerometer (Axivity, Newcastle, UK).ResultsEEG headbands and wrist accelerometers were sent to 348 participants with a total of 1116 nights of EEG recording and obtained. Of the 348 participants, 15 withdrew from the EEG component of the study; of the remaining 333, 316 (95%) completed at least 1 night of recording, and 301 (90%) obtained at least 1 night of recording with signal quality meeting quality control criteria (adequate signal quality in at least 1 frontal and 1 temporal electrode for at least 80% of the recording). For the wrist acclerometry data, 342 completed at least 7 days of wear meeting QC criteria.ConclusionFully remote sleep EEG and accelerometry data collection is feasible in a geographically dispersed cohort of older adults at high risk for dementia. The BHSP will provide an opportunity to assess whether EEG and accelerometric sleep features may predict the cognitive response to lifestyle interventions for dementia, or whether they themselves may respond to these lifestyle interventions.
APOE genotype‐specific lipidomic signatures in primary human hepatocytes
Authors: Patra Kalicharan , Almeida Francisco , Giannisis Andreas , Niesnerova Anezka , Nandakumar Renu , Ellis Ewa , Oliveira Tiago Gil , Nielsen Henrietta M. 
Published: December 2023

AbstractBackgroundApolipoprotein E (APOE) is primarily responsible for cholesterol homeostasis in the periphery and in the brain through independently regulated pathways, as it does not cross the blood‐brain barrier (BBB). Carriers of the APOE ε4 allele have a 3‐ to 15‐fold higher risk of developing Alzheimer’s disease (AD). Recently, we demonstrated that hepatic APOE4 was associated with alterations in AD‐relevant brain functions, suggesting clinical significance of plasma APOE, 90% of which is derived from the liver. How APOE genotype affects the hepatic lipidome is yet unknown. In this study, we assessed APOE genotype‐specific lipidomic profiles of primary human hepatocytes and their association with hepatic APOE.MethodWe conducted a lipidomic analysis of primary human hepatocytes isolated from 77 subjects by use of Ultra Performance Liquid Chromatography‐Tandem Mass Spectrometry. Lipid class levels over age across ε2/ε3, ε3/ε3 and ε3/ε4 genotypes were assessed using Pearson correlation analysis and between‐group comparisons for lipid class and species levels, controlled for demographic variables, were performed using one‐way ANOVA with Tukey HSD correction for multiple comparisons. We assessed hepatic APOE levels by ELISA in order to compare APOE expression between APOE genotypes and investigate correlations with lipid levels.ResultWe found APOE allele‐specific lipidomic patterns over age and between groups. APOE genotype differentially modulated the relationship between age and lipid levels across multiple lipid classes. The ε4 carriers had higher acylcarnitines (AC) and acylphosphatidylglycerol (AcylPG) as a class, as well as higher medium and long‐chain ACs, AcylPG, bis(monoacylglycerol)phosphate (BMP), monoacylglycerol and diacylglycerol species compared to ε2 carriers. Hepatocyte APOE levels decreased with age in the whole cohort, but correlated with monoacylglycerols (MG) and phosphatidylcholine (PC) only in ε4 carriers. We observed no differences in APOE hepatocyte levels specific to genotype or sex of the donor.ConclusionAPOE genotype dictates a differential lipidome in primary human hepatocytes but has no effect on APOE levels. The lipids involved suggest mitochondrial dysfunction with accompanying alterations in neutral lipid storage, reflective of a general disturbance of free fatty acid metabolism in human hepatocytes with the ε4 allele.