bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in the integrity of cortical and subcortical circuits in AD and MCI: Connectivity study in rs‐fMRI.
Authors: Rodriguez Keveen , Aponte Claudia , Quintero Carlos Andrés Andrés Tobón , Ochoa John F , Puche Aura C , Hidalgo Maria Jose 
Published: December 2023

AbstractBackgroundrs‐FC has been altered in AD continuum with hyper‐hypoconnectivity patterns attributed not only to regional changes, but to disruption of functional integration or aberrant connectivity between cortical and subcortical brain regions . This study seeks to find connectivity patterns in MCI and AD with a different network extraction approach taking each network as a whole and not separated into ROIs.Methodsrs‐fMRI data from ADNI3 and OASIS3 of 64/85 AD/Control subjects, 57/59 MCI/Control subjects from both repositories were preprocessed with the CONN toolbox. Resting state networks (RSN) were extracted by cGICA using GIFT toolbox (semi‐blind INFOMAX) with 300 ROI Set template with 14 RSN. A non parametric 2‐sample t‐test was applied using the SnPM tool, all analyses in SnPM were performed using 10000 random permutations and the anatomical association of each reported cluster is extracted from the AAL atlas using the xjView tool . Regions that had statistically significant clusters with p FWE<0.001 and with k> = 100 voxels were analyzed.ResultsThere were alterations in regions of every network for each groups comparison (p < 0.001). Several ROI were repeatedly altered in analyzed RSN, temporal pole, MTG, STG, cerebellar crus, OFC, PCC, MCC, precuneus, AG, SMG, SPL, IPL, SFG, MFG, IFG, thalamus, FG and posterior cerebellar lobe. Decreased/increased activation area, changes in activation intensity and reorganization of activation areas, specially reduced activation areas in AD and greater activation areas in MCI. The RSN with more changes in connectivity patterns were DMN, DAN/VAN, MTL, SAL and FPN.ConclusionChanges in connectivity in MCI and AD show reorganization of RSN related to enlargement, reduction or displacement of activation areas, the greatest amount of change was observed in MCI with increases in activation areas and in AD a general decrease in activation areas was observed, these alterations are consistent with the inverted u‐pattern that has been described in other studies . The common ROI we found altered had been related with accumulation and aggregation of p‐Tau and βA and this could be an explanation of connectivity changes duet to the neurodegeneration and synaptic dysfunction caused by this proteins
Spatial Transcriptomics of Human Postmortem Brain Tissue Uncovers Molecular Pathways Associated with Amyloid‐Beta Plaques
Authors: Avey Denis , Ng Bernard , Iatrou Artemis , Vialle Ricardo A , Lopes Katia de Paiva , Tasaki Shinya , Xu Jishu , De Tissera Sashini L , Flood Daniel , Bennett David A. A , Wang Yanling 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) pathologies include extracellular amyloid‐beta (A‐beta) plaques, intracellular neurofibrillary tangles, neuronal cell loss, and chronic glial inflammation. Recent studies profiling gene expression in human postmortem brain tissue have uncovered cell‐type‐specific changes in AD. However, these studies did not provide simultaneous, direct measurements of AD pathologies in the native microenvironment.MethodTo this end, we applied the 10X Genomics Visium platform to post‐mortem dorsolateral prefrontal cortex (DLPFC) from 20 ROSMAP participants with or without AD dementia. In total, we obtained spatial transcriptomic (ST) data for ∼260,000 tissue microdomains (“spots” comprised of ∼1‐10 cells).ResultWe clustered spots and annotated clusters according to expression of genes with known enrichment in anatomical layers (i.e. cortical layers 1‐6, meninges, and white matter). We deconvoluted the cell type(s) comprising each spot using cell2location, and found significant changes in the abundance of specific cell types in AD. Using a two‐stage pseudobulk regression approach, we identified hundreds of genes whose spatial expression is significantly associated with nearby A‐beta plaques and/or astrocyte reactivity (GFAP). A‐beta‐associated genes are enriched for diverse biological processes, including translation, metabolism, inflammation, gliosis, and immune cell infiltration. We also detected genes that distinguish A‐beta plaques surrounded by reactive glial nets. We validated the spatial expression pattern of a subset of plaque‐associated genes by RNAScope.ConclusionIn summary, our study reveals genes and pathways that shape molecular states in the spatial context of AD pathology. Our data represent a comprehensive application of ST technology in AD brains, providing a valuable resource for the research community.
Care partner burden and emergency service use: what is the link?
Authors: Lindauer Allison , Gothard Sarah , Bernard Hannah , Steele Joel S. 
Published: December 2023

AbstractBackgroundPersons with dementia (PWD) are significantly more likely to use emergency services (defined here as emergency department or urgent care visits) than age‐matched controls (1). The bi‐directional relationship between care partner (CP) burden and their PWD’s emergency service use is not well‐understood (2). A possible limiting factor is the infrequent assessment of emergency service use by the PWD and corresponding CP burden. Here, we used high frequency longitudinal data from the telehealth‐based Tele‐STELLA (Support via TEchnology: Living and Learning with Advancing ADRD) study (NIA R01AG067546) to examine the relationship between CP burden and PWD emergency service use.MethodCPs (n = 80; age = 65.7±11.6 years) completed weekly online “Orbit” surveys (3). The survey measures burden (ZBI‐4 [9±3.48 points]), cost‐of‐care, medication use, and emergency service use (4). Using R software (5), descriptive statistics and generalized mixed effect models were developed to examine the effects of CP burden on PWD emergency service use.ResultA median of 27 (min = 1;max = 61) weeks of CP responses were captured. Simple generalized mixed effects models showed a significant positive relationship between ZBI‐4 scores and emergency service use the week of event occurrence (β = 0.0853; p = 0.04). As ZBI‐4 scores increased, the greater the likelihood of an event. Additionally, a mixed effects model that examined the 5 weeks prior to emergency service use showed the absolute magnitude of change of ZBI‐4 scores had a negative relationship to the events (β = ‐0.393;p = 0.00;OR = 0.675). Taking the results of the two models together, as the range of burden narrowed towards higher ZBI‐4 scores, the chance of emergency service use increased.ConclusionHigh frequency electronic self‐reported data in this telehealth‐based study allowed for identification of emergent events closer to real time than the standard practice. As the range of CP burden scores decreased, trending toward higher burden, there was an increased likelihood of emergency service use occurring for the PWD. This information can be used to anticipate the likelihood of future events and create targeted interventions both for the CP and PWD prior to the need of emergency service use. Limitations in this analysis and gaps in research on this topic warrant further investigation.
Education, digital tools, and diagnostic support to increase PCP‐based cognitive testing in patients 65 years and older
Authors: Gitelman Darren R. , Mishos Jennifer , Canda Cristybelle‐Marie , Pagel Patti , Dimitris Lisa , Malone Michael 
Published: December 2023

AbstractIn the United States, primary care clinicians (PCPs) typically diagnose and treat most patients who have or who may be developing neurocognitive disorders (NCDs). However, as many as two‐thirds of patients remain underdiagnosed, misdiagnosed or experience a delay in the diagnosis. Many barriers to care have been cited for these failures in diagnosis, including PCP limitations in time and expertise, as well as inadequate technical, financial, and staffing resources. Diagnostic delays may particularly impact minority populations, exacerbating the disparate burden these communities bear from dementing disorders. In contrast, an early diagnosis is an impetus to advanced care planning, to strategizing for patient safety, and to initiating interventions that may preserve cognitive function and enhance quality of life.The main objective for this proposal is to increase the rate of cognitive screening in patients 65 years and older. PCP practices that serve diverse communities are early implementation sites. This proposal focuses on addressing barriers to testing by providing PCPs with educational resources to enhance the efficiency and quality of care for patients with neurocognitive disorders. The goal is to educate PCPs on the importance of early cognitive screening and to provide tools to help manage their patients with cognitive disorders and dementia more efficiently. Primary care providers are offered multiple educational and practice supports for managing patients who have an abnormal cognitive screen. The BrainCheck digital cognitive testing tool allows clinical support staff to rapidly test patients for cognitive impairment. Educational tools include succinct didactic lectures; a SharePoint site that serves as a resource hub for and weekly Project ECHO® based Memory Care Case Conferences (CME provided). EHR tools include simple order sets and templates. The practice support tool is an implementation of eConsults to quickly link PCPs to dementia experts in order to answer questions about patient care.The outcomes of this project measured in terms of PCP feedback, cognitive testing gains, educational participation, and tool usage will allow us to design more effective strategies for increasing cognitive testing and improving the management of patients with dementia at the health system level.
NEUROPROTECTIVE EFFECT OF PERILLYL ALCOHOL IN EXPERIMENTAL SPORADIC AD
Authors: Malik Shahid Mushtaq , Chauhan Dolly , Deshmukh Rahul Renukadas 
Published: December 2023

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuro inflammation. This study highlights the role of oxidative stress and inflammation in progression of AD where as Perillyl alcohol (POH) shows antioxidative & anti‐inflammatory properties.MethodSprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with Perillyl alcohol treated with three different doses of (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day. Weight measured on 1st and 28th day. Behavioral analysis done using Open Field Test and Morris Water Maze.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionStudy outcomes demonstrate neuroprotective potential of Perillyl alcohol against ICV‐STZ administration of streptozotocin induced behavioural and biochemical abnormalities. Biventricular STZ infusion produced significant impairment in learning, memory, cholinergic hypofunction and elevation in hippocampal oxidative stress in rats. Rats showed poor learning, memory and unable to discriminate between familiar & novel objects in MWM and ORT. POH administration significantly attenuated STZ induced biochemical consequences. Observed beneficial effects of POH include restored cholinergic functions and antioxidant mechanism
Dementia diagnosis using Addenbrooke’s Cognitive Examination in low literates and illiterates in three Indian languages
Authors: Paplikar Avanthi , Varghese Feba , Battacharyya Bidisha , Shukla Vasundhara , Tripathi Manjari , Biswas Atanu , Alladi Suvarna 
Published: December 2023

AbstractBackgroundWith a rising burden of dementia globally, there is a need to harmonize dementia diagnosis and research across diverse populations. Majority of dementia patients reside in low‐middle income countries (LMICs) such as India. Major challenges in the diagnosis of dementia in LMICs include the lack of a proper diagnostic tool for low literates and illiterates besides the lack of awareness of society about the disease. Addenbrooke’s Cognitive Examination‐III (ACE‐III) is a screening instrument with good validity and reliability to diagnose patients with mild cognitive impairment (MCI) and dementia. Although ACE‐III has been adapted to many languages both in India and worldwide, it has not been adapted for the low literate and illiterate population. The objective of the study is to i) develop a culturally relevant illiterate ACE‐III for the Indian context and standardize the instrument across three commonly used Indian languages: Hindi, Bengali, and Kannada; and ii) to establish the sensitivity and specificity of the illiterate Indian versions of ACE‐III to detect dementia and MCI.MethodThe illiterate version of ACE‐III was adapted from the literate version of ACE‐III based on the suggestions from multidisciplinary expert panel comprising cognitive neurologists, stroke specialists, speech–language pathologists and psychologists from different centres (see Figure 1). In total, 84 controls, 50 dementia, and 46 MCI patients were recruited across three cities in India for the validation study. Psychometric properties of adapted versions were examined, and their sensitivity and specificity were established.ResultThe sensitivity and specificity of illiterate ACE‐III in identifying dementia ranged from 93.3% to 99.9%, sensitivity for MCI ranged from 93.3% to 99%, and specificity from 72.7% to 99.9%. Optimum cut‐off scores were established (see Table 1).ConclusionThe adapted versions of illiterate ACE‐III have been standardized and validated for use across three Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context. The study provides a cognitive screening tool that can be used to uniformly diagnose cognitive impairment in people speaking different languages from both rural and urban populations located across India.
Neuroprotective Potential of Limonene in LPS induced Parkinson’s Disease in Rats
Authors: Sharma Pratyancha , Deshmukh Rahul Renukadas 
Published: December 2023

AbstractBackgroundParkinson’s disease is a hypokinetic disorder characterized by selective loss of dopaminergic in the substantia nigra pars compacta (SNPc) region of the mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, mitochondrial dysfunction, etc.MethodInfusion of LPS induced motor deficit and increased oxidative–nitritive stress in rats. Chronic treatment with limonene (25, 50 and 100 mg/kg/p.o.) for 21 days. LPS induced motor deficit and increase in striatal oxidative burden.ResultChronic treatment with limonene (25, 50 and 100 mg/kg/p.o.) for 21 days, significantly attenuated motor deficit and increased in striatal oxidative burden. Biochemically limonene significantly reduced the oxidative–nitrative stress, as evidenced by the decrease in malondialdehyde (MDA) and nitrite levels, and restored the reduced catalase, glutathione (GSH), and Superoxide dismutase (SOD) levels.ConclusionThe observed beneficial effects of limonene in motor defects may be due to its ability to reduce oxidative burden.
The Alzheimer Disease Sequencing Project: Enabling Discovery Through Diversity
Authors: Haines Jonathan L. 
Published: December 2023

AbstractBackgroundIn 2011, the U.S. congress passed the National Alzheimer’s Project Act to address the rapidly growing problem of Alzheimer disease and related disorders (ADRD). In response, the National Institute on Aging (NIA) initiated the Alzheimer’s Disease Sequencing Project (ADSP), a large‐scale effort to leverage genetics and genomics technology and expertise to unravel the underlying fundamental understanding of ADRD and accelerate the development of effective treatments for ADRD.MethodThe ADSP initially assembled existing datasets and now has invested heavily in developing new datasets (through the Follow‐Up Study (FUS) and Family‐Based Study (FBS) efforts) representing global diversity, now spanning nearly every continent. Necessary and critical infrastructure is in place, including the Genome Center for Alzheimer Disease (GCAD; DNA sequence processing), the NIA Genetics of Alzheimer Disease Data Storage Site (NIAGADS; data repository and access), and the National Centralized Repository for Alzheimer disease (NCRAD: sample repository). Data generation is performed through centralized laboratories for both whole genome sequencing (WGS) and plasma biomarkers. The resulting data are analyzed through multiple complementary consortia including those for data harmonization, genetic analysis, functional genomics, and computational analysis. This collaborative global initiative is coordinated through an oversight committee (the Executive Committee‐Cross Consortium Collaboration and Coordination; EC‐4C) with representation from all these important groups.ResultsData is released to the research community on a regular basis with the most recent release containing ∼37,000 WGS.ConclusionFuture releases will contain more detailed and harmonized clinical information, plasma biomarkers, WGS, and multi‐omics data, with the goal of having >100,000 samples with strong representation of global diversity.
Multi‐Ancestry Genetics for Alzheimer’s Disease: Alzheimer’s Disease Genetics Consortium
Authors: Jun Gyungah R 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) affects individuals of all races and ethnicities, yet large‐scale genetic research to compare genetic makeups for risk or protection of AD between multi‐ancestry datasets is limited. The Alzheimer’s Disease Genetics Consortium (ADGC) assembled the largest multi‐ancestry dataset including 56,241 subjects from non‐Hispanic Whites (NHW), African Americans (AA), Hispanics (HI), and East Asians (EAS) to understand ancestral similarities and differences in genetic risk and protective variants for AD.MethodWe established a Steering Committee with 5 members, 4 main Workgroups including Primary Meta‐Analysis, Follow‐Up Analysis, Secondary Analysis, and Method Evaluation, and 3 affiliated Workgroups consisting of Phenotype Harmonization, Imputation Development, and genome‐wide association study (GWAS)/whole genome sequencing (WGS) Integration. A new computing infrastructure was developed for shared analytic space on Amazon Web Services (AWS), where all members from different institutes accessed to genetic and phenotypic data and conducted analysis under the master analysis plan with centrally developed pipelines and scripts. We conducted ancestry‐specific GWAS using single nucleotide polymorphisms (SNPs) for AD, cross‐ancestry meta‐analysis of 4 ancestry GWASs, fine‐mapping for allelic heterogeneity in known and novel loci for AD, and pathway analysis.ResultWe confirmed 12 known including APOE ɛ4 and ɛ2 variants and identified 2 novel loci for AD in cross‐ancestry meta‐analysis with P<5.4×10−8. African and Asian ancestry subjects displayed greater heterogeneity in effect sizes and significant levels with the previously known AD loci for AD. Ancestry‐specific fine‐mapping indicated presence of potential distinct causal variants across different ancestry groups from multiple known AD loci. Two APOE alleles had greatest effect sizes among East Asians compared to others (EAS>NHW>AA>HI), while we failed to observe significant association signals with AD in SHARPIN and TREM2 regions from African Americans. Of two novel loci, the association signal in the LRRC4C‐API5 region was contributed from all four ancestry groups; in contrast, the signal in the LHX5‐AS1‐RBM19 region was predominantly from Hispanics.ConclusionGenetic risk profiling in multi‐ancestry datasets provided unique opportunity to understand ancestry‐specific and cross‐ancestry genetic risk factors for AD. Further evaluation of these established and novel loci for AD by integrating GWAS and WGS data from ADSP is underway
Factors Associated With Dementia‐Related Behaviors Among Caregivers Experiencing Poor Sleep
Authors: Patel Mansi , Papazyan Anna , Min Andrea , Winn Isabel , Josephson Karen , Teng Edmond , Alessi Cathy A , Martin Jennifer L , Song Yeonsu 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms of dementia are common and have the potential to negatively impact the physical and mental health of family caregivers, hindering their ability to provide care. Such impact may be worse among caregivers experiencing poor sleep. This study aimed to explore factors associated with the frequency of and caregivers’ distress to dementia‐related problematic behaviors.MethodThis was a cross‐sectional study, using data from a clinical trial of dyadic sleep intervention for persons living with dementia (PLWD) and their family caregivers. Dementia‐related behaviors were measured using a 24‐item, Revised Memory and Behavioral Problems Checklist (RMBPC): total scores of frequencies and caregivers’ distress; scores for three subscales (memory‐related, depression, and disruptive behaviors). Caregiver‐related variables included demographic background, Zarit Burden Interview (ZBI), Positive Aspects of Caregiving (PAC), Pittsburgh Sleep Quality Index (PSQI), and Center for Epidemiological Studies of Depression (CESD). Patient‐related variables included activities of daily living (ADLs), instrumental ADLs (IADLs), and Mini‐Mental State Examination (MMSE) scores. A total of 47 dyads were included in the analysis (caregivers: n = 29 spouses, n = 17 non‐spouses; 40% Whites). Pearson correlation analyses were conducted.ResultHigher ZBI and CESD scores were significantly associated with higher RMBPC frequency total (r = 0.41, r = 0.48, respectively; p<0.01) and caregiver distress total scores (r = 0.58, r = 0.43, respectively; p<0.01). Lower PAC (r = ‐0.31, p = 0.04) and higher MMSE scores (r = 0.37, p = 0.03) were also associated with higher caregiver distress total scores. ZBI and CESD scores were associated with RMBPC‐depression subscale scores (frequency/caregiver distress). There were positive associations between CESD and MMSE with RMBPC‐disruptive behaviors (frequency), and ZBI and PAC scores with RMBPC‐disruptive behaviors (caregiver distress). No patient or caregiver‐related factors were associated with RMBPC‐memory subscale scores. There was no significant association between PSQI scores and RMBPC total/subscale scores. Patient factors were not significantly associated with RMBPC frequency total or caregiver distress total scores.ConclusionDementia‐related problems, particularly depressive symptoms and disruptive behaviors of PLWD are associated with both positive and negative aspects of caregiving. Future studies will need to further examine how each RMBPC subscale of behavior contributes to caregiver burden or perceived caregiving experiences among family caregivers.