bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive phenotypes in probable mild Alzheimer’s disease
Authors: Dias Bruna Fugêncio , Dias Filipe Fulgencio , Costa Mônica Vieira , Ávila Rafaela , Miranda Millena Figueiredo , Miranda Mariana Figueiredo , Engelmann Gabriela Tomé Oliveira , Braga Nayara Rodrigues , Viana Bernardo de Mattos , Romano‐Silva Marco Aurelo , de Paula Jonas Jardim , Bicalho Maria Aparecida Camargo 
Published: June 2023

AbstractBackgroundNew technologies have helped the biological diagnosis of Alzheimer’s disease to make it more accurate over the years. However, establishing prognosis for each case is still a significant challenge, as there are different cognitive profiles in the same diagnosis. Also, there is no well‐defined standard for a cognitive profile that predicts future functionality impairment. In this sense, a better understanding of cognitive phenotypes can help establishing prognosis of Alzheimer’s dementia. Our aim with this study was to identify the main cognitive profiles of patients with amnestic variant of probable Alzheimer’s dementia at a mild presentation (CDR 1) with the amnestic variant. We verified the performance of these cognitive profiles applying the neuropsychological assessment.MethodThe study comprised 141 participants with probable Alzheimer dementia, recruited from a Reference Center for the Elderly in Brazil. We conducted a complete neuropsychological assessment evaluating the following domains: memory, executive functions, language, simple attention/processing speed, and visuospatial abilities. Initially, the data were transformed in z‐scores, considering age and education, according to references for the cultural adaptations and validations for the Brazilian population. We use the K‐Nearest Neighbors (K = 3) to solve the missing data problem. After preparing the base for cluster analysis, we performed the ward’s hierarchical method and the Euclidean distance to measure similarity. Finally, we performed comparisons of the groups using the Kruskal‐Wallis tests.ResultData analysis suggested existence of five cognitive subgroups (Figure 1). Bye general comparison, performed by the Kruskal‐Wallis test, we found the groups were different in the neuropsychological assessment instruments (p<0.001). Cognitive phenotypes varied about impaired and/or preserved ability, as well as impairment severity (Figure 2). The cognitive phenotypes were different considering educational level (Figure 3). We observed accentuated global impairment cognitive phenotype in a lower level of formal education group, and less accentuated impairment profiles in a higher formal education.ConclusionIn conclusion, we identified five Cognitive phenotypes which had differences in severity of cognitive symptoms, and impaired abilities. These Cognitive phenotypes were based on different degrees of severity in visuospatial ability, simple attention/processing speed, and planning and had different education level.
ADSP Whole Genome Sequencing (WGS) Release 3 data update from Genome Center for Alzheimer’s Disease
Authors: Leung Yuk Yee , Lee Wan‐Ping , Kuzma Amanda B , Gangadharan Prabhakaran , Issen Heather , Qu Liming , Sreedhara Mounica , Cantwell Laura B , Valladares Otto , Zhao Yi , Vardarajan Badri N , Kunkle Brian W. , Martin Eden R. , Naj Adam C. , Pericak‐Vance Margaret A. , Wang Li‐San , Schellenberg Gerard D. ,   Alzheimer’s disease Sequencing Project
Published: June 2023

AbstractBackgroundThe Genome Center for Alzheimer’s Disease (GCAD) coordinates the integration and meta‐analysis of all available Alzheimer’s disease (AD) relevant whole genome sequencing (WGS) data with the goal of identifying AD risk or protective genetic variants and eventual therapeutic targets. The WGS datasets are generated via the collaboration of scientists from the Alzheimer’s Disease Sequencing Project (ADSP) and GCAD. With the vision to minimize data heterogeneity, introduced by different sequencing protocols and machines, GCAD processes all samples using identical pipelines and performs quality assurance (QA) checks.MethodsRaw sequencing data (FASTQs or BAMs) were aligned to GRCh38/hg38 by BWA, and variant calling and joint genotyping were done by GATK. Furthermore, Smoove, Manta and Streka were applied to generate structural variant (SV) calls per sample. QA checks including sex, contamination and genotype concordance as well as the ADSP QC protocol were performed to evaluate the quality of samples and variants. To facilitate the access and usage of the big joint‐genotyped VCF files, we introduced a compact version for storing variant info and sample genotypes only.ResultsWe dropped 235 (1.3%) samples of poor coverage (<20x) or that failed QA checks, and we flagged 173 (1.0%) samples that were of borderline quality. As a result, the dataset (ADSP Release 3, 2021) includes 16,905 genomes from 17 diverse cohorts with 3 major ethnicities: 10,651 Non‐Hispanic Whites, 3,212 Hispanics and 2,874 African Americans. Data are deeply sequenced (average genome coverage: >30x). All samples’ CRAMs, gVCFs from GATK, and VCFs from the three SV callers were deposited into NIAGADS Data Sharing Service (DSS) (https://dss.niagads.org/) for public distribution. In addition, joint‐genotype VCFs are available in both compact and QC versions. This joint‐genotype VCF contains >206M bi‐allelic single‐nucleotide variants, 16M bi‐allelic indels and 28M multi‐allelic variants, with 96% of variants remaining after stringent QC.ConclusionThe ADSP and GCAD generate high quality genotype calls and SV calls. Currently the project is processing ∼37,000 WGS samples sequenced primarily through the ADSP Follow‐Up Study, which will contain a more ancestrally diverse set of populations. We anticipate this 2022 release will continue to benefit the research community studying AD genetics.
Human‐Derived Induced Pluripotent Stem Cells‐Based Disease Models of the Alzheimer’s Disease (AD) Patients Expressed AD Phenotypes and Responded to 17β‐Estradiol Treatment
Authors: Supakul Sopak , Maeda Sumihiro , Okano Hideyuki 
Published: June 2023

AbstractBackgroundNeuronal models of both familial and sporadic cases of Alzheimer’s Disease (fAD/sAD) were generated from the human‐derived induced pluripotent stem cells (iPSCs) of AD patients. Using this in vitro cellular models, AD‐like phenotypes was analyzed with or without 17β‐estradiol, the sex hormone that are supposed to be involved in the AD pathogenesis.Method5 lines of iPSCs comprised of 1 healthy control, 2 fAD, 2 sAD were differentiated to neurons with a newly established neuronal differentiation method. The AD‐like phenotypes such as secreted Aβ peptides and neuronal excitability were measured by ELISA and Ca‐imaging (Fluo‐8 indicator). In addition, the neuronal complexity and excitability were examined after long (4 days) and short (15 minutes) 17β‐estradiol treatment, respectively.ResultThe neurons were successfully induced from the iPSCs with the newly established differentiation method. The neurons induced from AD lines secreted more Aβ(1‐40) and Aβ(1‐42) peptides and increased Ca oscillations compared to the control line. The treatment with 17β‐estradiol to neurons promoted the neuronal complexity and cellular excitability.ConclusionNeurons derived from the iPSCs of the AD patients expressed AD phenotypes and responded to the treatment of 17β‐estradiol. Thus, this suggested the therapeutic effects of sex steroid hormones to AD can be evaluated in human cells. This enables us to examine the variability of estradiol response among patients and plan clinical trials based on the responsiveness.
Associations between Age and Cortical Thickness in Brain Regions Supporting Speech Motor Control
Authors: Eshghi Marziye , Li Binyin , Green Jordan R. , Salat David H 
Published: June 2023

AbstractBackgroundPrior research has demonstrated consistent associations between age and cortical thickness, as well as longitudinal reductions in cortical thickness in older adults (e.g., Salat et al., 2004; Storsve et al., 2014). To date, the aging of regions supporting speech production has not been directly investigated. Such information is, however, needed to differentiate age‐related cortical atrophy in speech regions from that occurring due to underlying neurodegenerative diseases. We examined cross‐sectional associations between age and cortical thickness of brain regions supporting speech motor control. These areas include subregions of the premotor cortex, primary motor area, supplementary motor area, pars opercularis, posterior inferior frontal sulcus, and insula as defined by the Directions Into Velocities of Articulators (DIVA) model ‐ a model for neural representation and mechanisms of speech motor control (Tourville & Guenther, 2011).MethodThe data were obtained from the Alzheimer’s Disease Neuroimaging Initiative GO/2 (ADNI). Participants included 163 (77 M, 86 F) cognitively intact adults aged 56‐89 years (Mean = 73.45, SD = 6.23). All participants were right‐handed and had at least 12 years of education (Mean = 16.53, SD = 2.55). Whole‐brain T1‐weighted MRI images were acquired by a 3‐Tesla Siemens scanner. FreeSurfer software was used for cortical surface reconstruction and to extract the cortical thickness of speech regions as identified by the SpeechLabel Parcellation System (Cai et al., 2014) developed based on the DIVA model.ResultSignificant associations between age and cortical thickness was observed in subregions of left premotor cortex, primary motor area, supplementary motor area, and presupplementary motor area with more limited effects in the right hemisphere. Cortical thickness of pars opercularis, posterior inferior frontal sulcus, and insula did not show significant changes over the aging process. Cross‐sectional interactions were found with regions in the left hemisphere being thicker at younger ages and having a larger negative age slope compared to their corresponding regions in the right hemisphere.ConclusionThe findings of the study suggest that certain speech‐related regions show atrophy with aging, however, these changes are not uniform. In addition, laterality in cortical thickness of speech regions at younger ages was observed to diminish over the normal aging process.
Feasibility of using wearable technology to monitor agitation and sleep in patients with Alzheimer’s dementia: Lessons learned
Authors: Okhravi Hamid , Gupta Ajay K , Jain Shubham , Maly Kurt J , Nesbitt Christianne , Shivajirao Shreyas Gujjar , Murthy Thrupthi Narayana , Wainwright Lavinia , King Diamond 
Published: June 2023

AbstractBackgroundIndividuals with Alzheimer’s dementia (AD) often go through a period of significant behavioral and psychological symptoms including agitation. This can lead to impaired daily functioning, prolongation of hospitalization, early institutionalization, and higher mortality. The integration of biomedical data acquisition systems and information technology enables continuous real‐time monitoring of physiological data in daily life.MethodThis feasibility study is part of a clinical trial that examines the effects of THC‐free CBD oil on agitation in patients with AD (NCT04436081), involves caregiver/care‐recipient dyads and the use of technology to capture agitation during a 14‐week period. Participants are given 2 Fitbit versa 2 (each includes a 3‐axis accelerometer and an optical heart rate monitor), a smartphone, a tablet, and a digital timer. Participants’ Fitbit are paired with their smartphone, while the caregivers’ FitBit is paired with their tablet. Participants include males/females over 50 years old, with the diagnosis of AD, a MMSE score ≤28 & ≥4, and agitation measured with an NPI agitation/aggression subscore >3. Each dyad completes 24 forms/questionnaires throughout the study electronically via provided apps. Caregivers are instructed to send a real time electronic alert when agitation episodes happen.ResultSo far, we have enrolled 26 dyads. For this report we have collected data on 22 participants with 140 million data points for limb movement and heart rate, and 969 nights of sleep data records. Overall compliance with wearable use was 77% of the time, with 82% in 11 participants, 65% in 8 participants and 32% in 3 participants. Compliance with electronic form/questionnaire completion was 87%. Electronic alert for agitation episodes were recorded by the caregivers only 50% of time.ConclusionThis study explores the feasibility and acceptability of using technology (wearables, electronic form data completion and submission, sleep, and real time agitation episode collection) for a 16‐week period in AD patients with agitation and their caregivers. We found high acceptability of wearing the Fitbit by AD patients with agitation. The primary issues interfering with data collection and device compliance were device battery life and memory, remembering to wear the device after charging, and technical fault in capturing the data.
Model on Impingement and consequences of Alzheimer’s disease in community‐ introductory study.
Authors: Chandran Niviya Seenivasa 
Published: June 2023

AbstractBackgroundAlzheimer disease demands salutation and envisioning the cause for the disease. Despite the evolving scientific discoveries, the inhabitation among the global population reminds hiking alarmingly. The track of ways the spread of disease should leave a hint for the further research on the origin of the disease.MethodThis is a speculation much closure to current environment, to analyze effect and the pace of spread over a community. Penna model of biological aging [1] and model of colonization (lattice model) [2] are primitive base. For the model both inherited and non‐ inherited Alzheimer disease is taken into account and is obtruded into the lattice simulated on external factors such as age, genome, genetic mutation, mating partner, offspring and visualizing the change in population, symptoms and progress of the disease.ResultOutcome helps in providing an introductory knowledge on the impact Alzheimer creates in the society. It shows the growth on the level of symptoms in the population, the influence of the inheritance on the population and their progress during the course of time. The symptom to analyze the level of disease at respective age of the individual is monitored. The executions for variations in the input arguments are studied to determine the effect of disease from different perspectives.ConclusionThe Preliminary results show reasonable changes on the level of symptoms for the inherited Alzheimer’s disease. The results shell out some introductory ideas about growth of the level of symptoms of AD in the population during the course of the disease increasing number of offspring and number of mating will give a greater view of the consequences in the model and is predictable for the current scenario.1. Stauffer, D. (2007). The Penna model of biological aging. Bioinformatics and Biology Insights, 1, 117793220700100005.2. Mroz, I., &Pękalski, A. (1999). Model of populations colonizing a new habitat. The European Physical Journal B‐Condensed Matter and Complex Systems, 10(1), 181‐186.
Towards data‐driven video analysis for quantification of nocturnal sleep disturbance in dementia
Authors: Mohammadi Sara Mahvash , Monica Ciro Della , Revell Victoria Louise , Atzori Giuseppe , Dijk Derk‐Jan , Wells Kevin 
Published: June 2023

AbstractBackgroundSleep disturbance is common among people living with dementia as well as their caregivers. Non‐contact video technology can be used to characterise such disturbances as well as quantifying sleep quality by measuring the number of sleep body positions (poses). Such an approach may be beneficial for home‐based longitudinal clinical monitoring of sleep pattern changes and disturbances at all stages of dementia. Here we present our pilot results of a personalised data‐driven method applied to video data for quantification of sleep disturbance comparing older and younger participants.MethodData were collected in two separate studies which included an overnight 10‐12 hour laboratory sleep recording from thirteen older (65‐80 years, 9 male:4 female) and eleven younger (18‐34 years, 7 male:4 female) participants in a dedicated sleep facility. A data‐driven analysis using Principal Component Analysis and k‐means clustering was applied to infrared video data extracted from a clinical polysomnography (PSG) system. The data‐driven analysis automatically determined statistically significant groupings or clusters of unique body poses for each individual. Pose number, number of pose transitions, pose duration, and pose transition duration were computed for each participant.ResultThe number of data‐driven poses in older and younger participants was remarkably similar with 15.2±3.9 and 15.8±1.8 (mean±SD) poses per participant, respectively. However, the older group had a higher number of pose transitions (33.0±8.82) compared to the younger group (23.9±6.83) (p = 0.03). A significant 20% difference (p = 0.03) in the average duration of each body position was observed, with 62.3±7.1 minutes and 78.9±15.9 minutes for the older and younger groups, respectively (see Figure 1 and Figure 2). Pose transition duration was 19.2±7.25 seconds and 14.6±4.32 seconds for the older and younger groups, respectively where they were not significantly different.ConclusionAlthough the number of body positions did not vary significantly between the two cohorts, the older group changed body position more frequently and it took them longer to do so. Data‐driven automated analysis of video‐based sleep monitoring holds significant promise for quantifying age‐related and inter‐individual differences in sleep behavior.
Sex differences in stroke‐induced cognitive impairment and the impact of Mir20a‐3p treatment in middle‐aged Sprague Dawley rats
Authors: Sampath Dayalan , Markowsky Kylee Grace , Branyan Taylor E , Sohrabji Farida 
Published: June 2023

AbstractBackgroundStroke is a leading risk factor for dementia. Our previous studies show that the small non‐coding RNA, mir20a‐3p, is neuroprotective for stroke and reduces sensory‐motor impairment in the acute phase (Branyan et al., 2021). In this study, we used a battery of tests to assess the integrated functioning of affective and cognitive circuits after stroke in males and females, as well as the impact of mir20a‐3pMethodMiddle‐aged (acyclic) females and males were subject to ischemic stroke using endothelin‐1 in the left middle cerebral artery (MCA) region. Mir20a‐3p mimics or scrambled oligo was administered i.v. 4h and 24h after stroke with a supplementary dose at 60d. Long‐term cognitive changes were assessed by contextual fear conditioning (CFC) and the novel object recognition test (NORT).ResultBoth males and females showed significant sensory‐motor impairment due to stroke in the acute phase, which was attenuated by Mir20a‐3p treatment. In the chronic phase, cognitive function was assessed by cued and contextual fear conditioning, evaluated by percent freezing during acquisition, retrieval, and extinction of fear memory. When measured 30, 60 and 100d after stroke, retrieval of fear memory was significantly reduced over time in sham and stroke males and females. However, linear regression analysis revealed that among females, the rate of decline of fear memory was significantly accelerated in the stroke group that received scrambled oligo treatment, while the rate of decline in the Mir20a‐3p group was similar to the sham group, indicating a protective effect of this drug. Surprisingly, stroke+ scrambled treated male rats did not show an accelerated decline. We further examined declarative memory (as assessed by the Novel Object Recognition Task) and noted that there was a decline over time in both males and females.ConclusionThis study shows that cognitive impairment is selectively affected by stroke and that despite the fact that acute sensory‐motor impairment is seen to a similar extent in males and females, stroke significantly affected the retrieval of fear memory in females but not males. Moreover, treatment with Mir20a‐3p abrogated this effect of stroke.
Early synaptic gene expression downregulation in the frontal cortex distinguishes Alzheimer’s disease from normal aging in a genetically diverse mouse population
Authors: Dunn Amy R , Ouellette Andrew R , Hadad Niran , Zhang Jigang , Philip Vivek M. , O'Connell Kristen , Kaczorowski Catherine C. 
Published: June 2023

AbstractBackgroundThe frontal cortex is critical to many cognitive processes and is vulnerable to pathology and neurodegeneration in Alzheimer’s disease. Cortical dysfunction and impaired connectivity in the frontal cortex have also been observed in “normal” age‐related cognitive decline, suggesting common mechanisms contributing to both age‐related and AD‐related cognitive decline. The divergence that may lead to AD versus normal aging, however, is unclear.MethodHere, we have used genetically diverse mouse populations modeling either AD or normal aging, the AD‐BXDs and their nontransgenic littermates (Neuner et al, Neuron, 2019). We measured cognitive function from early (6mo) to middle (14mo) adulthood to capture presymptomatic and advanced AD stages and early aging processes. We performed bulk RNAseq from the frontal cortex, followed by age‐ and AD‐related differential gene expression analysis and Weighted Gene Coexpression Network Analysis (WGCNA) to identify genes and gene networks whose expression is associated with normal and pathological aging.ResultIn both differential gene expression analysis and WGCNA, we found common mechanisms underlying normal aging and AD (e.g., upregulation of inflammation‐related gene pathways). We also found that downregulation of genes and gene networks associated with synaptic function specifically occurred in AD and not in normal aging, suggesting that early synaptic dysfunction and/or synaptic loss is a unique feature of AD that distinguishes it from normal aging processes. Based on differential gene expression, network analyses, presence of high‐impact variants across the BXD panel, and association with cognitive function, we identified one gene candidate, B230209E15Rik, a lncRNA, as a potential regulator of synaptic gene networks in the frontal cortex that promotes resilience to cognitive decline in AD.ConclusionOverall, our data indicate that cognitive aging and AD may share common neuroimmune activation and dysregulation of neuronal maintenance, but that AD, and particularly late AD, is uniquely characterized by synaptic dysfunction. We nominate an intriguing candidate, B230209E15Rik, as a potentially key driver of synaptic gene regulation in the frontal cortex. In order to elucidate the mechanism by which this gene may promote cognitive resilience in AD, we are currently validating this finding in vivo.