bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID19 and cognitive impairment ‐ A follow‐up study with cognitive and neuroimaging evaluation of the Clinical Hospital of São Paulo
Authors: Spera Raphael Ribeiro , Luca e Tuma Raphael , Rodrigues Júlia Chartouni , Peixoto Satiko Andrezza Takano , Neto Adalberto Studart , Coutinho Arthur , Miotto Eliane C , Brucki Sonia Maria Dozzi 
Published: December 2023

AbstractBackgroundPost‐COVID19 syndrome is characterized by signs and symptoms that occur within 3 months of the onset of COVID19 and last for at least 2 months. Cognitive impairment has frequently been associated with COVID19 with descriptions of attentional, executive, memory, and language disorders. Moreover, some morphological and metabolic changes have been described in MRI and FDG PET‐CT, respectively. There is no formal treatment for this condition.MethodWe selected patients less than 65 years of age with COVID19 at least 3 or more months of symptoms and no more than 6 months, no relevant structural brain lesions, no record of neurodegenerative disease. A cross‐over design study was performed with neuropsychological rehabilitation. They were evaluated 3 times by a neurologist (0, 3, and 6 months) with specific cognitive battery tests and questionnaires and then by a neuropsychologist for evaluation and training. Finally, most patients underwent neuroimaging with cranial MRI and FDG PET CT or MRI.Result44 patients performed the first baseline evaluation, 34 matched inclusion criteria and were referred to neuropsychological rehabilitation. 20 underwent functional and structural neuroimaging. This sample had a mean age of 44 (SD8.9) years, 61% of females, 16.1 (SD5.1) years of education, 17.6% of hypertension, 2.9% diabetes, 11.8% dyslipidemia and 23.5% obesity. Cognitive evaluation depicted that 90.6% had memory complaints; MMSE of 27.7 (SD1.8); delayed recall of 8.68 (SD1.6) out 10 in the brief cognitive screening battery; semantic verbal fluency of 18.24 (SD5.1); lexical fluency of 31.7 (SD11.7); forward digit span 6.62 (SD0.7); backward digit span 4.82 (SD 1.3); clock drawing test of 9.12 (SD1.6) and Boston naming test‐15 of 14.06 (SD1.5). 46.9% reported more than 5 points on the depression scale and 41.2% somnolence on the Epworth scale. 60% had abnormal findings (hypometabolism) in brain FDG PET, 16% with frontotemporal involvement, 33% basal ganglia, 8% frontoparietal, 41% cerebellum, 8% parietal only, 8% frontalmedial, and 25% temporal. Some (33%) had mixed patterns.Conclusionpost‐COVID19 syndrome and cognitive impairment are relatively common and we need prospective studies in low and middle‐income countries to understand the cognitive profile, structural and metabolic patterns in neuroimage, and the role of neuropsychological rehabilitation.
Call for Collecting and Reporting Disaggregated Data for Centering Racial Inclusion and Equity in the U.S. and Globally: Examining Multimorbidity and Risk for Cognitive Impairment in the Asian American Populations
Authors: Zanwar Preeti Pushpalata , Taylor Robyn , Heyn Patricia C 
Published: December 2023

AbstractBackgroundAsian American subgroups are underrepresented in Alzheimers Disease and Related Dementias (ADRD) research in the U.S. and globally.MethodOur approach was threefold: First, we identified data collection and reporting gaps for ADRD among Asian Americans in the U.S from multiple nationally representative surveys, e.g. Health and Retirement Survey, Medical Expenditure Panel Survey, and the Census. Second, we examined multi‐morbidity (e.g. diabetes, hypertension, cardiovascular disease and stroke) burden among a specific group of Asian Americans, South Asian Indians. Third, we provide knowledge gaps and recommendations for inclusion of Asian Americans to center racial equity in ADRD science.ResultDespite being a highly heterogeneous group and diverse in terms of culture, diet, language, Asian Americans are lumped together in national surveys. The three national surveys we examined in the U.S. have not collected disaggregated data on Asian Americans, a group that is growing in the U.S. Moreover, there is a lack of disease registers for different groups of Asian Americans which makes it difficult to assess and quantify the prevalence and burden of ADRD in this group. Due to a lack of systematic data collection efforts, the extent of dementia burden and classification of dementia cannot be accurately examined in the sub‐groups of Asian Americans. The data gaps in the collection and reporting of data on sub‐groups of Asian Americans prevent from designing culturally and linguistically sensitive interventions which are highly needed for sub‐groups of Asian Americans. South Asian Indians, a sub‐group of Asian Americans, considered to be of higher socioeconomic background in the U.S. were seldom omitted from the minority classification despite having a higher burden of multiple chronic conditions such as diabetes, hypertension, cardiovascular disease, and stroke, i.e. multi‐morbidity combinations which can greatly contribute to increased ADRD risk in this sub‐group.ConclusionThere is a critical need for the collection and reporting of disaggregated ADRD data on Asian Americans for centering racial equity in ADRD science in the U.S. Such efforts will aid in the understanding of mechanistic pathways for vascular cognitive impairment via inclusion of unique Asian populations that have been underrepresented in ADRD research both in the U.S. and globally.
Identifying human‐relevant genetic interactors of APOE using genetically diverse mouse strains
Authors: Onos Kristen D , Elk Kevin J , Uyar Asli , Keezer Kelly J , Marola Olivia J , Kasper Rachel , Pandey Ravi S , Carter Gregory W , Sasner Michael , Howell Gareth R 
Published: December 2023

AbstractBackgroundAPOEe4 is the greatest risk factor for late‐onset Alzheimer’s disease (AD), accounting for ∼30% of genetic risk and significantly decreasing age of onset. APOE is implicated to play central roles across multiple pathways such as neuroinflammation, lipid metabolism and vascular health. Current mechanistic work has introduced humanized APOE alleles in mouse models of AD on a single laboratory mouse strain, C57BL/6J (B6). Recent work from our lab has taken advantage of genetically diverse wild‐derived strains which were captured from different geographical regions and then inbred, thus, their genomes are closer to recapitulating combinations that would exist in the natural world. Here, we seek to identify and validate human‐relevant genetic interactors of APOE within these contexts and in the presence of amyloid.MethodNovel wild‐derived mice were developed by backcrossing the respective strain (PWK/PhJ, WSB/EiJ) to B6.APOEe4 (N5). These were crossed with congenic APP/PS1 carriers, and offspring intercrossed to generate cohorts of 4‐ and 8‐month males and females homozygous for APOEe4, with and without APP/PS1. A cohort of B6.APOEe4 carrying APP/PS1 were also generated for comparison. Neuropathology was assessed along with blood chemistry, and transcriptional profiling was performed on brain hemispheres.ResultBrain transcriptional profiling revealed that APOEe4 had the greatest impact on differential gene expression (dE) in the PWK genetic context at both timepoints, with the strongest effect in females. Comparison with AMP‐AD human‐derived consensus clusters also indicated the broadest overlap when variants were present in the PWK context. Furthermore, APOEe4 genotype was sufficient to cause neuronal damage at 8 months, despite other studies indicating neuronal resilience to amyloid and aging in PWK. In both WSB and B6 carrying APP/PS1, APOEe4 increased the incidence and severity of cerebral amyloid angiopathy (CAA). Further neuropathological assessments are ongoing, and will be correlated with dE.ConclusionThis work highlights the importance of assessing risk alleles for AD in a variety of genetic contexts. We have also created genetically diverse panels of mice that carry humanized amyloid beta and humanized tau in that hope that these strains will provide an improved preclinical platform for therapeutic discovery and testing.
Bilingualism is associated with a later age of symptom onset in bilinguals with Alzheimer’s disease positive biomarkers
Authors: Grasso Stephanie M , Marques‐Kiderle Sonia Karin , Calabria Marco , Sala Isabel , Rodríguez‐Baz Íñigo , Zhu Nuole , Arranz Javier , Rubio‐Guerra Sara , Illán‐Gala Ignacio , Carmona‐Iragui Maria , Alcolea Daniel , Fortea Juan , Lleo Alberto , Santos‐Santos Miguel A 
Published: December 2023

AbstractBackgroundCognitive reserve factors may provide protection against the manifestation of symptoms associated with neurodegenerative diseases (Stern, 2012). Although results are mixed, it has been observed that bilingualism may contribute to cognitive reserve by delaying the age of onset of symptoms of Alzheimer’s disease (AD) (e.g., Alladi et al., 2013, 2017; Bialystok et al., 2007, 2010; de Leon et al., 2020).MethodsIn the current study, we examined the effects of bilingualism on age of symptom onset in a large cohort of Catalan‐Spanish bilingual speakers (n = 446) with positive Alzheimer’s disease cerebrospinal fluid biomarkers. We conducted a retrospective study in which participants were characterized as bilingual or monolingual based on self‐report at the time of neuropsychological testing. Analyses of covariance (ANCOVA) were conducted to investigate the association between bilingualism and age of symptom onset while controlling for a proxy of disease severity (Mini‐Mental State Exam (Folstein et al., 1975) and education.ResultsThe results of our ANCOVA revealed that Catalan‐Spanish bilinguals with AD positive CSF biomarkers present with a significant, approximate two‐year delay in symptom onset relative to monolingual speakers (see Figure 1; bilingual M = 71.41, monolingual M = 69.75).ConclusionAlthough previous reports in the literature indicate that bilingualism may delay the onset of symptoms on the order of 4‐5 years, we observed an approximate 2‐year difference in the onset of symptoms. This finding is consistent with previous literature conducted in Catalan‐Spanish bilinguals (Calabria et al., 2020) and likely reflects that even ‘monolingual’ speakers in this particular sociocultural context are exposed to more than one language and may exhibit a form of passive bilingualism.
A Randomized, Double‐blind, Sham‐controlled, Adaptive‐Design Pivotal Trial of Sensory Stimulation in Subjects with Alzheimer’s Disease
Authors: Boasso Alyssa , Houser Celine , Hajos Mihaly , Newberger Jennifer , Seshagiri Chandran , Leach Julia , Konisky Alexandra , Galley Alyssa , Hempel Evan , Dickson Samuel P. , Hendrix Suzanne B. , Malchano Zach , Megerian Jonathan Thomas 
Published: December 2023

AbstractBackgroundIn three prospective clinical trials (Overture: NCT03556280, Etude: NCT03661034, Flicker: NCT03543878) non‐invasive, visual and auditory gamma (40 Hz) sensory stimulation diminished Alzheimer’s disease (AD) symptoms, including a reduction in decline in cognitive and functional symptoms. These trials initiated the design of the Cognito Therapeutics sponsored Hope pivotal trial which examines the safety and efficacy of Cognito Therapeutics’ Sensory Stimulation System.MethodThe US‐based multicenter Hope trial will randomize (1:1) approximately 500 subjects aged 50 and older diagnosed with mild to moderate AD (MMSE 15‐26) and will stratify them to active and sham in a blinded manner across MMSE score ranges: 15‐20 and 21‐26. Subjects in both study arms will self‐administer therapy via the Sensory Stimulation System for 60 minutes daily for 12 months. An interim analysis will employ the promising zone methodology, allowing the sample size to be adjusted if the effect is trending toward success, but additional subjects are needed to maintain greater than 80% power.ResultThe primary outcome measure will be the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS‐ADL) test. Changes in function and cognition will be evaluated using a combined statistical test for ADCS‐ADL and the Mini Mental State Exam (MMSE). The key secondary outcome is change in cognition using the MMSE. Other clinical efficacy assessments include instrumental activities of daily living (IADL), Zarit Burden Index (ZBI), the Clinical Dementia Rating Scale (CDR) and The Neuropsychiatric Inventory anxiety subscale (NPI – Anxiety). Key biomarker assessments include whole brain, white matter, and hippocampal volume and occipital cortical thickness. Sleep fragmentation will be assessed in a subgroup of subjects using actigraphy. Exploratory measures will include additional brain structural change, plasma biomarkers, EEG assessed coherence, and at‐home tablet‐based tasks. Safety will be evaluated via routine clinical laboratory assessments, review of adverse events, concurrent medication use, physical and neurological exams, vital signs, MRI, and a suicidality scale.ConclusionThe Hope pivotal trial is designed to demonstrate the efficacy and safety of daily in‐home gamma sensory stimulation in AD patients to support a regulatory filing with the FDA.
Assessment of brain oxygen extraction in aging and Alzheimer’s disease with MRI images
Authors: Hosseini Seyyed Ali , Servaes Stijn , Therriault Joseph , Tissot Cécile , Rahmouni Nesrine , Macedo Arthur C. , Lussier Firoza Z , Stevenson Jenna , Wang Yi‐Ting , Arias Jaime Fernandez , Aumont Etienne , Socualaya Kely Quispialaya , Nazneen Tahnia , Stevenson Alyssa , Gauthier Serge , Pascoal Tharick A. , Rosa‐Neto Pedro 
Published: December 2023

AbstractBackgroundThere is a growing body of evidence suggesting changes in blood flow and metabolism as a trigger of the cascade of events leading to Alzheimer’s disease (AD). Oxygen extraction fraction (OEF) MRI images provide valuable information about the brain’s metabolism and blood flow in stroke, brain injury, and recently neurodegenerative diseases. However, OEF is a research tool, and its clinical utility is still being evaluated. Here, we aimed to assess brain oxygenation in aging and AD using OEF images. We test the hypothesis that OEF reduction is associated with the clinical stages of AD.MethodA cohort of 310 subjects with cognitively unimpaired (CU) (n = 182), mild cognitive impairment (MCI) (n = 80), and AD (n = 48), were recruited. All participants received 3D gradient‐recalled echo sequence MRI. All OEF images were constructed by QSM+qBOLD model with CCTV (Temporal clustering, tissue composition, and total variation) (Figure1). Eighty‐two various brain regions of interest (ROI) and 6 Braak ROI were investigated in the current study.ResultOur results demonstrated that the OEF mean value in almost all of the brain ROI encompassed the lowest amount of OEF in AD compared with MCI and CU. In most parts of the brain, the OEF mean value was AD<MCI<CU including bilateral caudate. However, in other parts of the brain, the OEF mean value increased from CU to MCI and then dipped to lower than CU in AD including the bilateral hippocampus, which clearly shows that brain metabolism and blood flow are decreasing in AD (Table1).ConclusionOEF is an affordable and relevant non‐invasive MR approach to assess brain metabolism during disease progression or therapeutic interventions. OEF decreased in symptomatic cases. Further studies should explore the mechanisms underlying increased OEF in MCI. Our results support the potential of OEF to improve our understanding of metabolic changes associated with AD pathophysiology.
Cognitive Domains and Functional Assessment Questionnaire (CDFAQ): accuracy and correlation with IQCODE
Authors: Maia Isabelle de Aguiar , Tavares Caio Peixoto , Ferreira Jéssica Diniz , Gomes Giulia Costa , Mutz Bruna Hellen Barbosa , Guerson Giovanna Lins , Diniz Júlia Moreira , Engelmann Gabriela Tomé Oliveira , de Paula Jonas Jardim , Diniz Maissa Ferreira , Romano‐Silva Marco Aurélio , Bicalho Maria Aparecida Camargos , De Mattos Viana Bernardo 
Published: December 2023

AbstractBackgroundThe Cognitive Domains and Functional Assessment Questionnaire (CDFAQ) assesses cognitive domains and functional decline based on the DSM‐5 criteria for Neurocognitive Disorders. It has two versions, one for the patient (CDFAQ‐PV) and another for the informant (CDFAQ‐IV) assessing: Complex Attention (CA), Executive Functions (EF), Learning and Memory (LM), Language (L), Perceptual‐Motor Domain (PM) and Social Cognition. Recently, the CDFAQ was translated and adapted to English.MethodTo describe the performance of the CDFAQ‐PV and CDFAQ‐IV assessing Brazilian older adults compared with the Informant Questionnaire on Cognitive Decline in the Elderly Long Version – IQCODE‐LV. This study was approved by the ethical committee of the UFMG and the CDFAQ was applied to 132 subjects in the University Hospital. The CDFAQ‐PV was applied to 66 older adults and the CDFAQ‐IV, as well as the IQCODE‐LV, to their 66 respective informants. Non‐parametric correlation with IQCODE‐LV and accuracy assessment by Receiver Operating Characteristic (ROC) with cutoff for dementia were performed.ResultThe median age of the patients was 70.5 years (IQR = 13.5) and 5 years of schooling (IQR = 7), while the informants had a median age of 55 years (IQR = 24.5) and 12 years of schooling (IQR = 8). The CDFAQ‐IV showed a strong positive correlation (Rho:0.708, p<0.001) to IQCODE‐LV. Interestingly, the LM Domain had an even higher positive correlation (Rho:0.758, p<0.001), while the CDFAQ‐PV had moderate (Rho:0.405, p = 0.001) and its LM Domain had a weak (Rho:0.348, p = 0.004) positive correlations. The CDFAQ‐IV had a good area under the curve (0.871) as well as its LM (0.861), L (0.832), EF (0.854) Domains, while SC, PM were considered only fair. The cutoff values were assessed by Youden’s J statistics: CDFAQ‐IV Total score ≥66.5 (SE:88.9%; SP:89.6%) and the LM Domain score ≥11,5 (SE:88.9; SP:77.1%) had the best performances.ConclusionThe strong correlation of the CDFAQ‐IV and its LM Domain to the IQCODE‐LV, as well as the good area under the curve, points a good accuracy for assessing neurocognitive disorders when applied to their informants. Nevertheless, this is still preliminary data, and more assessments in different scenarios, as well as, comparing with objective cognitive assessment is still needed.
Perseverations and switching during a verbal fluency task
Authors: Dubey Neha , Basu Jayanti , Ghosh Amitabha 
Published: December 2023

AbstractBackgroundPerseverations during a verbal fluency task can be immediate or delayed. There is a general agreement that delayed perseveration may occur due to impaired working memory (WM). However, experiments to establish this have been complex and time consuming. It is also not known if perseverations are caused by similar mechanisms of impairment in WM in healthy controls and in the cognitively impaired. On a semantic fluency task, switching between subcategories produces an automatic self‐generated interference. Impairment in WM capacity may lead to perseveration when switchback to a previous subcategory occurs. The number of switches preceding this switchback may also be considered to extend the WM load and result in perseveration. We hypothesize that individuals with WM impairment (aMCI and AD) are likely to perseverate only after few initial switches. In contrast, a healthy control (HC), with a relatively intact WM, may have fewer perseverations for similar number of switches and may be able to sustain more switches quantitatively.ObjectiveTo study how clusters and switches during verbal fluency tasks can help understand WM contributions to perseveration in patients with cognitive impairment as opposed to cognitively normal controls.MethodWe studied three groups, aMCI (n = 30), AD (n = 30) and HC (n = 60) based on their performance on a semantic fluency task along with tests of executive function. Our primary analysis, focussed on number of switches in between subcategories of index word and first perseverative error. Additionally, average word distance between the two was analysed. Finally, relationship between perseveration, switching and switch back was also studied.ResultsForty‐eight percent of perseverative errors occurred after the third switch for individuals with cognitive decline. In contrast, thirty‐five percent of cognitively healthy perseverated after three switches and forty‐three percent after five. Further, perseverations in HC group, were found to be more attributable to longer subcategory lists exceeding the normal word list span, even within the same cluster. Finally, at a given distance between index word and perseveration, cognitively impaired performed hierarchically worse than HC.ConclusionThese findings suggest that switching across subcategories creates self‐generated interference which further amplifies working memory impairment among the cognitively impaired.
A role of tau‐induced astrocyte dysfunction and senescence in AD
Authors: Makhlouf Haneen , Dorigatti Angela O , Hussong Stacy A , Perez Viviana , Kayed Rakez , Galvan Veronica 
Published: December 2023

AbstractBackgroundUnder certain conditions and during aging, cellular stress and damage can trigger cellular senescence, an irreversible state of cell cycle arrest accompanied by the expression of proinflammatory mediators known collectively as the “senescent‐associated secretory phenotype” (SASP). In Alzheimer’s disease (AD), neuronal tau becomes hyperphosphorylated and misfolded, forming pathogenic soluble aggregates (tau oligomers) and destabilizing the microtubule cytoskeleton. Pathogenic soluble tau is released from neurons during neuronal activation and is transmitted in a prion‐like fashion to postsynaptic cells. In addition to neurons, tau is expressed in a variety of brain cell types including astrocytes. In the present study, we tested the central hypothesis that soluble pathogenic tau can be transmitted to astrocytes and that tau transmission to astrocytes induces cytoskeleton destabilization and cellular dysfunction, contributing to the progression of AD.MethodsTo test the molecular consequences of tau transmission, we treated primary human astrocytes with purified tau oligomers. We used advanced biochemical tools, immunocytochemistry, and live‐cell microscopy to measure cell and nuclear size, cell cycle arrest, and SASP activation. We also co cultured human astrocytes undergoing tau‐induced senescence with primary mouse or non‐human primate neurons to determine the functional impact of senescent astrocytes on neurons, then utilized immunocytochemistry and 3D image analyses to measure parameters of dendrite and spine morphology.ResultsWe found that pathogenic soluble tau is readily transmitted to primary human astrocytes, and that pathogenic tau transmission triggers phosphorylation of endogenous astrocyte tau, leading to the destabilization of the microtubule cytoskeleton. Further, we found that transmission of pathogenic tau to astrocytes potently upregulated multiple markers of cellular senescence, demonstrating for the first time tau‐induced astrocyte senescence. Density of dendritic spines and dendritic area were pronouncedly decreased in neurons co‐cultured with astrocytes undergoing tau‐induced senescence.ConclusionWe showed transmission of pathogenic tau to human astrocytes and that this event triggers astrocyte senescence in mouse models of AD tauopathy. Our data suggest that senescent astrocytes may be critical mediators of neuronal dysfunction in AD tauopathy.