bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Brain Kidney Axis Vascular Cross Talk
Authors: Gupta Aditi 
Published: December 2023

AbstractChronic kidney disease (CKD) is associated with cognitive impairment and dementia; 87% of patients on chronic dialysis have some degree of cognitive impairment. The prevalence of CKD increases with age and approximately 40% of persons aged >60 years have CKD. With increasing life expectancy, prevalence of both CKD and dementia are expected to increase.CKD and Alzheimer’s disease (AD) share common risk factors. Patients with CKD are older, and have multiple comorbidities such as hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity, making CKD a model for accelerated aging, inflammation, and vascular dysregulation. Inflammation and vascular dysregulation can disrupt blood brain barrier, decreased kidney function can influence amyloid clearance, an important AD biomarker. Patients with CKD have alterations in cerebral blood flow, brain white matter integrity, brain neurochemicals, and blood brain barrier permeability‐ findings that are similar to those seen in AD.We investigated brain alterations seen in CKD before and after successful kidney transplant and found reversibility of brain alterations, and improvement in cognitive function after kidney transplantation. Further, we examined whether the cognitive impairment in CKD is due to comorbidities such as hypertension or due to decreased kidney function. In addition, for the first time, we have shown evidence for disruption of blood brain barrier in patients with CKD. With the high prevalence of CKD in the older population, and the strong association between decreased glomerular filtration rate and cognitive impairment, understanding the mechanisms underlying cognitive impairment and developing strategies to mitigate the risks in the CKD population is important.The potential reversibility in brain alterations seen in CKD after a kidney transplant indicate an opportunity to develop strategies for management of cognitive impairment.
Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants
Authors: Trainer Anne , Xu Wanwan , Chase Alison , O'Dell Ryan S. , Tun Samantha M , Li Joyce S , Ju Suyeon , van Dyck Christopher H , Mecca Adam P , Fredricks Carolyn 
Published: December 2023

AbstractBackgroundWhile the spread of tau throughout the brain is well‐characterized in amnestic Alzheimer’s disease (AD), tau staging remains less clear for those suffering from clinically heterogeneous variants including logopenic variant primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA). We created a method to identify local maxima of tau SUVR (“epicenters”) in participants with early‐stage clinically heterogeneous AD with the goal of classifying participant subtypes based on the functional connectivity of these epicenters.MethodWe obtained 18F‐MK‐6240 tau PET scans from 10 participants with diagnoses of early‐stage clinically heterogeneous AD (5 lvPPA, 5 PCA, Clinical Dementia Rating 0.5‐1.0). We identified three local maxima of tau SUVR with a minimum specified distance of 20mm between them for each participant (Fig. 1). We then derived each epicenter’s functional connectivity in 1000 healthy controls using Neurosynth and sorted participants into subtypes based on the overlap of these functional connectivity maps.ResultParticipants with lvPPA showed highest tau burden in the posterior temporoparietal and temporoocciptal regions, left side predominant, and participants with PCA displayed highest tau burden in the bilateral parietooccipital cortex, frontal eye fields, and fusiform gyrus. We identified nine distinct subtypes of functional connectivity and most participants’ epicenters participated in more than one subtype. All subtypes highlight functional connectivity networks that have been associated with language and, or visuospatial processing. The most common subtype (seen in 7 of the 10 participants and 11 of the 30 epicenters) features connectivity within the bilateral occipital lobule, fusiform gyrus, and superior parietal lobule (Fig. 2).ConclusionWe used a novel method to identify tau “epicenters” in the brains of participants with early‐stage clinically heterogeneous AD. Using these epicenters, we derived functional connectivity maps, which we then grouped into nine subtypes across participants. We will shortly begin collecting longitudinal tau PET in these clinically heterogeneous individuals with AD, allowing us to assess the extent to which tau spreads along the functional connectivity maps predicted by each participant’s epicenters and whether individually tailored epicenters outperform subtype classification. This work could serve as the basis for patient‐specific biomarkers of expected disease spread in clinically heterogeneous AD.
Investigating the effects of aerobic exercise primed anodal transcranial direct current stimulation on γ‐aminobutyric acid concentrations in mild vascular cognitive impairment
Authors: Wong Melissa , Near Jamie , Tumati Shankar , Gaur Amish , Siddiqui Mehreen , Gallagher Damien , Oh Paul I. , Marzolini Susan , Black Sandra E. , Swardfager Walter , Graham Simon J. , Ramirez Joel , Andreazza Ana C. , Rapoport Mark J. , Marotta Giovanni , Herrmann Nathan , Goubran Maged , Rajji Tarek K. , Lanctôt Krista L. 
Published: December 2023

AbstractBackgroundMild vascular cognitive impairment (mVCI) is characterized by minor deficits in cognition and memory due to underlying vascular pathology. Anodal transcranial direct current stimulation (atDCS), a non‐invasive neuromodulation technique, has been demonstrated to improve cognition. The effects of atDCS have been suggested to be mediated by γ‐aminobutyric acid (GABA)–a major inhibitory neurotransmitter associated with cerebral perfusion and oxygenation, and cognition and memory. However, previous studies have reported mixed results regarding changes in GABA concentrations following atDCS. Physical activity has been reported to increase cortical GABA levels, and in particular, aerobic exercise (AE) is associated with improved cognition in older adults. Preliminary data from an ongoing trial (EXPRESS‐V) was used to evaluate whether GABA concentration in the motor cortex was altered following AE and/or atDCS and whether this was associated with changes in global cognition in mVCI.MethodIn this double‐blind, randomized clinical trial, participants received one of four interventions for two weeks: AE and atDCS, AE and sham atDCS, exercise education and atDCS, or exercise education and sham atDCS. mVCI was determined based on a modified Gorelick criteria. At baseline and endpoint, GABA concentration in the motor cortex was measured using magnetic resonance spectroscopy and quantified with the Mescher‐Garwood point resolved spectroscopy pulse sequence, and global cognition was assessed using the Montreal Cognitive Assessment. Wilcoxon signed rank test was used to determine changes in GABA concentrations (ΔGABA). Spearman correlation was used to determine the association between ΔGABA and changes in global cognition (ΔMoCA).ResultTen participants have enrolled so far, with nine participants having completed the study (22.2% female, age = 66.4(9.8), years of education = 8.8(3.4), 55.6% White, baseline MoCA score = 22.8(3.1)). To date, ΔGABA was insignificant between baseline and endpoint (Z = 23.0, p = 0.953). However, a positive trend between ΔGABA and ΔMoCA was observed (ρ = 0.650, p = 0.058).ConclusionPreliminary results from nine participants showed a positive trend between ΔGABA and ΔMoCA. Since the trial is ongoing, with the target of recruiting 80 participants by 2024, analyses on unblinded data upon study completion will determine whether AE and atDCS leads to greater ΔGABA, and whether this is accompanied by greater ΔMoCA in mVCI.
Autophagy dysregulation in human fibroblasts from Niemann‐Pick type C patients
Authors: Pradel‐Bernal Tamara Patricia , Alcala‐Flores Rebeca‐Leticia , Gomez‐Virgilio Laura , Silva‐Lucero Maria‐del‐Carmen , Rivera‐Osorio Jared , Cardenas‐Aguayo Maria‐del‐Carmen 
Published: December 2023

AbstractBackgroundNiemann‐Pick disease type C (NPC) results from a mutation in the gene that encodes endolysosomal cholesterol‐transport proteins NPC1. NPC is characterized by the accumulation of unesterified cholesterol and other lipids within the cell causing the impaired function of lysosomes and the autophagy flux. The symptoms of the disease are variable and may include: enlarged liver or/and spleen, learning difficulties, seizures, gait problems, dementia, and loss of muscle tone, among others. Macroautophagy is the main recycling pathway of organelles and cellular components in mammalian cells to obtain primary elements in stress conditions such as the absence of nutrients and maintaining cellular homeostasis. During disease, it also helps to get rid of toxic misfolding protein aggregates. Many neurodegenerative diseases are characterized by autophagy impairment.MethodIn this study, we worked with 3 skin fibroblast cells lines from apparently healthy subjects and 3 from Niemann‐Pick’s patients to corroborate altered autophagy flux made an autophagy induction by chloroquine (10 uM) and serum starvation, first we performed the Cyto‐ID autophagy (Enzo) detection kit and then we analyzed by Western blotting the expression of proteins that are involved in the autophagy pathway to find the altered mechanisms.ResultChloroquine treatment induced a significant decrease in the viability of NPC cells as compared to controls, which correlates with an increase in cytoplasmic autophagy vacuoles (Avs) and an increase in LC3‐II. Also, there was an increased trend in LC3‐II, ATG5, ATG16‐L1 in NPC cells cultured in the presence and absence of nutrients. No significant changes were observed in the expression of p62 between NPCs and control cells.ConclusionNPCs are more sensitive to autophagy induction by Chloroquine than control cells, as demonstrated by morphology (increase in AVs) and LC3‐II, ATG5 and ATG16L1 expression, detected by Western blotting.
Predictive Ability of Physical Performance Measures in Identifying Falls in Older Adults with Dementia: A Systematic Review and Meta‐Analysis
Authors: Chan Wayne LS , Pin Tamis , Chan Jason YH , Siu George CH 
Published: December 2023

AbstractBackgroundFalls are very common in older adults with dementia and pose a serious threat to their physical and psychological health, functional independence, and life expectancy. Reduced physical performance (i.e., gait, balance, muscle strength, and mobility impairments) has been shown to be a risk factor for falls in older adults with dementia. Identifying measures of physical performance that can predict falls in this population is crucial for clinicians and researchers to select appropriate assessment tools to evaluate their fall risk and design effective fall prevention strategies.The objective of this systematic review and meta‐analysis is to determine whether physical performance measures commonly used in clinical settings can predict falls in older adults with dementia.MethodMEDLINE, Embase, PsycINFO, CINAHL, SPORTDiscus, Cochrane Library, and PEDro databases were searched from inception until 27 January 2023 (Prospero Registration: CRD42022303670). Longitudinal cohort and cross‐sectional studies that evaluated the associations between physical performance measures and falls in individuals aged ≥ 65 with dementia were included. The standardized mean difference (SMD) in each physical performance measure between fallers and non‐fallers was calculated.ResultTwenty‐five studies were included in this systematic review and meta‐analysis (Figure 1). Five‐time chair stands (SMD: 0.23; 95% CI: 0.01, 0.45), postural sway on floor with eyes open (SMD: 0.25; 95% CI: 0.07, 0.43), postural sway on foam with eyes open (SMD: 0.45; 95% CI: 0.25, 0.66), Berg Balance Scale (SMD: ‐0.52; 95% CI: ‐0.87, ‐0.17), and Timed Up and Go test (SMD: 0.34; 95% CI: 0.03, 0.64) predicted falls in older adults with dementia (Figure 2). Sensitivity analyses showed that gait speed could predict falls in those who were staying in residential care facilities or hospitals (SMD: ‐0.21; 95% CI: ‐0.38, ‐0.05). Concerns about the risk of bias in the included studies were noted, and the quality of evidence was generally very low to low.ConclusionChair stands, postural sway on floor and foam, Berg Balance Scale, and Timed Up and Go test can predict falls in older adults with dementia. Gait speed can only predict falls among those who are staying in residential care or hospital units.
Development of co‐designed resources to provide guidance for people living with dementia and their carers on medication management during hospitalisation
Authors: Clough Alexander J , Gnjidic Danijela , Manias Elizabeth , Jeon Yun‐Hee , Jokanovic Natali , Thompson Jane F , Schneider Carl R , Chen Timothy , Sawan Mouna J 
Published: December 2023

AbstractBackgroundPeople with dementia are more likely to experience medication‐related harm than people without dementia at transitions of care. However, medication management guidance is often not provided to people with dementia and carers during hospitalisation. We aimed to co‐design novel medication management resources for people with dementia and carers during hospitalisation.MethodThis is a mixed‐methods study involving five stages: i) generate resource topics by content analysing a scoping review and a previous qualitative study exploring carers’ medication management experiences at discharge; ii) develop the first version of the resources; iii) obtain input from dementia expert advisory panels; iv) undertake focus groups with people with dementia, carers, and healthcare professionals; v) complete quantitative analysis of readability, understandability and actionability, and suitability of the resources through validated tools. Focus groups were content analysed to explore participants’ perceptions of the resources’ topics, content, and layout, and how well they meet their needs. The resources were edited during each stage, a graphic designer modified the layout, and final copies produced.ResultWe derived six resource topics including: participating in shared decision‐making; identifying common medications that may affect cognition; and describing hospital processes and the person’s role. The advisory panels recommended introducing informed consent and the discharge summary and medications list in the resources. Two focus groups have been conducted with carers (n = 4) and healthcare professionals (n = 3). Participants felt the topics generated would be useful and beneficial. They suggested: modifying the title to appeal to all supporters of someone with dementia (not just formal carers); listing more medications that may affect cognition; and limiting medical terminology. They recommended providing the resources at admission for referral throughout the hospital stay. The resources were of an adequate reading level, understandable, actionable, and suitable.ConclusionResources containing information on shared decision‐making, informed consent, medications that may affect cognition, and support to improve involvement in medication decisions would be valuable to people with dementia, carers, and healthcare professionals. The next stages are to conduct user‐testing on how well key information can be located and understood and evaluate participants’ knowledge and engagement in shared decision‐making after using the resources.
Fixel based analysis of white matter alterations in Mild cognitive impairment and Alzheimer’s disease
Authors: Bhattarai Anjan , Maillard Pauline , Decarli Charles , Fan Audrey 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia, and is associated with altered white matter (WM) microstructures in the brain (Clerx et al., 2012; Jack Jr et al., 2013). Diffusion weighted imaging (DWI) is a non‐invasive method of examining white matter alterations in AD and Mild cognitive Impairment (MCI). DWI based Fixel‐based analysis (FBA) is a novel method that enables the investigation of fibre specific WM alterations at the microscopic level. In this study, we investigated fibre tract‐specific changes in the whole‐brain WM, in individuals with MCI and AD using DWI based FBA.MethodN = 102 participants (>70 years) from the University of California Davis Alzheimer’s Disease Research Center were included in this study, including 34 individuals with AD, 34 with MCI, and 34 control subjects. DWI data were obtained on a 3T Siemens TimTrio scanner (resolution = 2mm, 60 directions, at b = 1000s/mm2) and pre‐processed using MRtrix3 (Tournier et al., 2019). Single‐Shell 3‐tissue CSD (SS3T‐CSD) was performed to obtain Fibre Orientation Distributions (FODs) related to WM as well as for gray matter and cerebrospinal fluid compartments in all voxels, using MRtrix3Tissue. A study‐specific unbiased FOD template was generated and used for FBA processing. Whole‐brain FBA maps, including fibre density (FD), fibre cross‐section (FC), and combination of fibre density and cross‐section (FDC), were generated. Statistical analyses were performed using connectivity based fixel enhancement at each fixel using general linear model (Raffelt et al., 2015)(Figure1).ResultThe whole‐brain FBA showed significant reduction in FD in individuals with AD compared to MCI, in regions including splenium of corpus callosum, fornix, and the left uncinate fasciculus (Figure2). Furthermore, AD individuals showed significant reduction in FD in the left uncinate fasciculus compared to controls. We observed subtle reduction in FD and FDC metrics (although not statistically significant after FWE corrections) in regions including corpus callosum, forceps majors, and uncinate fasciculus in AD(Figure3). We did not observe significant difference in FC between groups.ConclusionFBA‐derived measures demonstrated sensitivity in detecting microstructural white matter alterations in AD. These findings highlight the utility of FBA as a promising tool for providing valuable insights into pathophysiologic changes in AD.
Association of depression dimensions with cognitive functioning in community‐dwelling oldest old adults of LifeAfter90 study
Authors: Soleimani Laili , Hirst Andrew K , Gilsanz Paola , Whitmer Rachel A. , Corrada María M. M. , Beeri Michal S 
Published: December 2023

AbstractBackgroundOldest old adults (90+) are the fastest growing population with high burden of cognitive impairment and depression. Though depression is a known risk factor for cognitive impairment, it is unclear how each of the predominant depression dimensions correspond with cognitive outcomes.MethodsWe used baseline data from LifeAfter90 study, a racially and ethnically diverse cohort of community‐dwelling adults aged 90 and above. Participants are longtime members of Kaiser Permanente Northern California Health System without a dementia diagnosis in their medical record. Verbal episodic memory, semantic memory, and executive function were assessed with the Spanish & English Neuropsychological Assessment Scale and averaged as a composite measure of global cognition. Depression was measured by the Geriatric Depression Scale (GDS) and the dimensions (Dysphoria, Withdrawal‐Apathy ‐Vigor (WAV), Anxiety, Hopelessness and Subjective Memory Complaint) calculated based on GDS‐items. Generalized linear mixed models estimated associations between global and domain‐specific cognition and depression dimensions adjusting for age, sex, education, and race.ResultsParticipants (n = 960, mean age = 92.4 ± 2.3 yrs, 61.56% female) were 24% Asian, 23% Black, 19% Latino, and 27% White. The most common reported GDS items were “decreased energy” (52.45%), preference to “stay home” (46.31%) and “dropped activity” (40.0%) and 25% reported memory complaints (Figure 1). Hopelessness was associated with worse executive functions (P< 0.001) but not with other cognitive domains nor with global cognition. Dysphoric mood, WAV, and anxiety were not associated with any of the cognitive outcomes (Table 1). Conversely, subjective memory complaints was associated with worse global cognition, executive function and verbal episodic memory, but not with semantic memory.ConclusionCharacterizing the dominant depression dimensions may be informative in predicting pattern of cognitive deficits. Perceived memory impairment in the oldest old was supported by objective deficit in episodic memory and executive functions suggesting that subjective reports should be taken as a valid early sign of impairment in this population. Further exploration of the longitudinal association of depression dimensions with cognitive domains is warranted.
Blood transcriptomics differentiate tau positive discordant and concordant individuals
Authors: Souza Lara Angi , Schlickmann Thomas , Machado Luiza Santos , Pascoal Tharick A. , Ant Marco , Bastiani De , Zimmer Eduardo R 
Published: December 2023

AbstractBackgroundLevels of soluble hyperphosphorylated tau (p‐tau) in the cerebrospinal fluid (CSF) and tau tangles measured by positron emission tomography (PET) are used to determine tau positivity in Alzheimer’s disease (AD). However, a mismatch between CSF and PET positivity occurs in some cases. In fact, it is thought that CSF tau biomarker abnormalities may precede changes in tau‐PET imaging. With this in mind, the aim of our study was to examine the blood transcriptomic phenotypes in individuals presenting tau positivity biomarker discordance.MethodBlood transcriptomics data from 64 individuals (cognitively unimpaired = 31 and cognitively impaired = 33) were obtained from the ADNI database. We divided these individuals into negative (CSF‐PET‐), discordant (CSF‐PET+ and CSF+PET‐) and positive group (CSF+PET+) to tau biomarkers. We also performed differential expression analyses (DEA) using the limma package. Additionally, we conducted a KEGG pathway enrichment analysis using altered genes obtained from DEA (p‐value < 0.05). Amyloid B42, total tau, Mini Mental State Examination, Clinical Dementia Rating Sum of Boxes, APOE4 status, education, and gender difference in the groups were described in Fig1. Data were analyzed with Pearson’s Chi‐squared test and Linear Model ANOVA. All statistical analyses were performed in R.ResultsOur analysis revealed that discordant and positive individuals had, respectively, 1191 and 314 DEGs if compared to negative individuals. Interestingly, we found 324 DEGs in common between them (Fig2A‐C). In the KEGG functional enrichment analysis (Fig3), we observed that the main terms were enriched in the tau discordant individuals were related to aminoacids metabolism and inflammation (Fig3A). In the CSF+/PET+ individuals pathways related to calcium signaling and viral response were the most altered compared to CSF‐/PET‐ (Fig3B).ConclusionOur results indicate that blood transcriptome differs among tau negative, discordant and positive individuals. This suggests that multiple biological pathways in the blood are dependent on tau changes. Further investigation of DEGs clusters possibly could demonstrate new insights about tau mechanisms involved in the disease.