bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiological correlates of objective memory impairments in community‐dwelling older adults at risk of dementia
Authors: Gonzalez‐Montealegre Rodrigo A , Gonzalez‐Hernandez Alfredis , Bonilla‐Santos Jasmin , Parra‐Rodriguez Mario A 
Published: December 2023

AbstractBackgroundThe electrophysiological correlates of Short‐Term Memory Binding (STMB) have been previously investigated in older adults at risk of dementia (i.e., Mild Cognitive Impairment ‐MCI). Pietto et al. (2016) reported reduced early electrophysiological activity (100‐250 ms) over fronto‐central (FC) and parieto‐occipital (PO) regions in MCI patients recruited from clinic. We investigated if such an electrophysiological pattern is also observed in a larger sample of community‐dwelling older adults with MCI who had not sought medical advice.MethodsA sample of 215 community‐dwelling older adults were recruited into the study. They were assessed with a battery of cognitive tests including CERAD (Aguirre‐Acevedo et al., 2016), the Addenbrooke’s Cognitive Examination (ACE‐R), the STMB Task, clinical, and functional scales. The STMB task assesses the ability to detect changes between two consecutive visual arrays of coloured shapes. Changes consisted of shapes swapping colours (the binding condition). Time‐locked EEG signals were collected while participants performed the STMB task. Monte Carlo tests and non‐parametric bootstrapping running 1000 permutations revealed electrodes and time windows of relevance.ResultsA group of 108 participants met classical criteria for MCI (Petersen, 2004; Winblad et al., 2004). They showed impaired STMB abilities. ERP analyses revealed significant Group x Time Windows interactions (p<0.01). Early ERP showed reduced neural recruitment (MCI<HC) on the left PO and right centro‐parietal (CP) (300‐500ms) regions during shape‐colour encoding, and on PO bilaterally and left FC during retrieval (150‐450ms). Late ERP showed increased neural recruitment (MCI>HC) on right fronto‐central (FC) regions (900‐1200ms) during shape‐colour encoding, and on left FC and PO regions (872‐1200ms) during retrieval.ConclusionAltered spatio‐temporal dynamics underpinning STMB deficits in MCI patients followed a pattern similar to that described by Pietto et al. (2016). Of note, we observed hyper‐recruitment for late ERP linked to encoding and retrieval over anterior and posterior regions of the STMB network. Such hyper‐recruitment may reflect compensatory changes in the early stages of MCI. These results confirm the usefulness of EEG‐based cognitive biomarkers to screen community‐dwelling older adults at risk of dementia.Aguirre‐Acevedo et al. (2016). Int. Psychogeriatr, 28(3), 503‐510.Pietto et al. (2016). Journal of Alzheimer’s Disease, 53(4), 1325‐1340.
Differential effects of neuronal Cdkn2a over‐expression in mouse brain
Authors: Finneran Dylan , Desjarlais Taylor , Morgan Dave , Gordon Marcia N. 
Published: December 2023

AbstractBackgroundAging is the primary risk factor for Alzheimer’s disease (AD). With aging, senescent cells accumulate in the body and the brain. Cells that become senescent cease contributing to homeostasis but do not typically undergo apoptosis. Prior studies have identified a broad association between increased cellular senescence and AD‐like pathology and have identified senescent cells in AD patient brain and mouse models of AD‐like pathology. However, contributions of senescent cells to disease progression remains uncertain.MethodThe two gene products of the senescence regulator Cdkn2a (p16‐Ink4a and p19‐Arf) were overexpressed using intracranial delivery of adeno‐associated viral vectors (AAV). Mice were injected with 2 µL of 1×1013, 5×1012, or 1×1012 vg/mL of AAV‐Arf and tissue was collected two months post‐injection. Control mice were injected with AAV empty capsid. Brain weights, NeuN IHC, and p19‐Arf mRNA were assessed. A second cohort of mice was injected with AAV‐Ink, AAV‐Arf, AAV‐Ink & AAV‐Arf (co‐injection), or AAV‐GFP and followed for four months post‐injection. We assessed body mass, brain mass, NeuN IHC, and expression of senescence‐induced genes by PCR‐array and qRT‐PCR. A third experiment over‐expressing p19‐Arf in PS19 mice is ongoing.ResultWe observed that animals over‐expressing p19‐Arf failed to gain body mass up to four months post‐injection. Post‐mortem, we found that over‐expression of p19‐Arf is toxic to neurons, reducing gross brain mass and NeuN area staining. Furthermore, a greater number of differentially regulated genes were observed in mice over‐expressing p19‐Arf than in mice over‐expressing p16‐Ink4a. We confirmed increased expression of the senescence‐regulator p21 in mice over‐expressing p19‐Arf, but not p16‐Ink4a, by qPCR. In a separate experiment, we replicated the finding of neurotoxicity induced by over‐expression of p19‐Arf at only two months post‐injection and determined the optimal viral titer to administer that induces significant over‐expression with minimal neurotoxicity for use in future studies.ConclusionAs observed in cultured cells, over‐expression of Cdkn2a seems to increase markers of senescence. Effects on tau pathology will be examined in the PS19 mouse model of tauopathy. Cell type‐specific expression in neurons, astroglia, and microglia will be used to elucidate cell type specific contributions to senescence‐induced disease progression.
Neuropsychiatric symptoms are Predictors of Disturbed Sleep in Mexican American Caregivers
Authors: Cantu Phillip A , Milani Sadaf Arefi , Mroz Emily , Pan Yulu , Miner Brienne , Sheehan Connor , Jody Sharninghausen 
Published: December 2023

AbstractBackgroundCaregivers of people living with dementia are more likely to experience disturbed sleep compared to non‐caregivers. Mexican‐Americans may be especially at risk due to low rates of nursing home use even in advanced dementia, when behavioral symptoms are most apparent. Few studies have evaluated predictors of disturbed sleep in this high‐risk group.MethodUsing data from the 2015 wave of the Hispanic Established Population for Epidemiologic Study of the Elderly, a representative sample of older Mexican‐Americans and their caregivers in the southwestern United States (n = 460), we examined the association of care recipient neuropsychiatric symptoms with disturbed sleep in caregivers. Care recipients’ behavioral symptoms of cognitive decline were assessed using the caregiver‐reported Neuropsychiatric Inventory. We examined caregivers’ depressive symptoms as an additional stressor. Potential “buffers” against sleep disturbances included communal support (neighbor, church, social services) and respite care. Caregivers were classified as having “highly disturbed sleep” if they reported disturbed sleep three or more days a week, and were compared to caregivers with “non‐highly disturbed sleep” (reported disturbed sleep less than three days a week). We used multivariable logistic regression to examine the association between behavioral symptoms and highly disturbed sleep, controlling for demographic factors and care buffers.ResultCaregivers in the sample were predominantly spouses or adult children of their care recipients. They had a mean age of 59.7 and7 8% were women. Care recipients were a mean age of 90 and 65% were women. Caregivers with disturbed sleep (12% of the sample) reported significantly more care recipient NPI symptoms, distress from symptoms, and more depressive symptoms. In the regression model accounting for all predictors, the number of NPI symptoms and depressive symptoms were associated with higher odds of disturbed sleep, while communal support was associated with lower odds of disturbed sleep. Use of respite care did not show associations.ConclusionBehavioral symptoms of cognitive impairment are associated with sleep disturbance in Mexican American caregivers. Though respite has been described as a crucial resource for caregiver sleep health, communal supports were more significantly associated with sleep l. These results should inform the development of culturally‐competent resources for Mexican‐Americans.
Evaluation of the Causal Effects of COVID‐19 on Alzheimer’s Disease: LD Score Regression Analysis and Mendelian Randomization Study
Authors: Chen Jingchun , Cummings Melika J. , Zhang Mark L. , Lu Yimei , Cammann Davis B , Do Jenifer , Zheng Jennifer J. 
Published: December 2023

AbstractBackgroundCOVID‐19 is an acute respiratory infection that is frequently followed by short‐ or long‐term neurological abnormalities, and may increase the risk of developing Alzheimer’s disease (AD). However, the genetic and biological mechanisms underlying this risk are poorly understood. Utilizing publicly available large genome‐wide association studies (GWAS), we explored the possible causal effects of three different COVID‐19 phenotypes on AD.MethodCOVID‐19 GWAS data from European cohorts were obtained from the Host Genetics Initiative website in its most recent release (HGI7‐EUR) with three phenotypes: 1) critically ill COVID‐19 (case/ctrl: 13,769/1,072,442); 2) hospitalized COVID‐19 (case/ctrl: 32,519/2,062,805); 3) regular COVID‐19 infection (case/ctrl: 2,475,240/12,597,856). European AD GWAS data were retrieved from Jansen et al.’s study (case/ctrl: 71,880/ 383,378). The linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) methods were used to analyze the genetic correlation and possible causal effects among the three COVID‐19 phenotypes and AD.ResultLDSC indicated that AD had significant positive correlations with the critically ill COVID‐19 (FDR = 0.021, z = 2.45, rg = 0.224) and hospitalized COVID‐19 (FDR = 0.020, z = 2.71, rg = 0.241) phenotypes, but not regular COVID‐19 infection (FDR = 0.133). On the other hand, MR with the fixed‐effects inverse variance weighted method indicated that regular COVID‐19 had some causal effect on AD (P = 0.019, beta = 0.032). Marginal causal effects on AD were also found from critical COVID‐19 (P = 0.072, beta = 0.008) and hospitalized COVID‐19 (P = 0.082, beta = 0.013). In addition, MR with weighed mode method showed significant effects on AD from three COVID‐19 phenotypes (P = 0.040‐0.003), while MR‐Egger method did not show any significance between the two diseases.ConclusionUsing LDSC and MR approaches, our preliminary data identified a genetic correlation between hospitalized and critically ill COVID‐19 phenotypes and AD, and possible causal effects on AD through genetic variants shared with standard COVID‐19 infection. With the continuing COVID‐19 epidemic and the high comorbidity and mortality of AD from COVID‐19 infection, our observations emphasize the urgency of understanding the overlapping genetic risk for the two diseases. Further studies might shed light on the long‐term neurological influence of COVID‐19 and further provide strategies for disease intervention against COVID‐19 and AD.
In vivo characterization of tau accumulation in patients with frontotemporal dementia: A PET study with 18F‐florzolotau
Authors: Kubota Manabu , Endo Hironobu , Takahata Keisuke , Tagai Kenji , Suzuki Hisaomi , Onaya Mitsumoto , Sano Yasunori , Yamamoto Yasuharu , Kurose Shin , Matsuoka Kiwamu , Seki Chie , Shinotoh Hitoshi , Kawamura Kazunori , Zhang Ming‐Rong , Takado Yuhei , Shimada Hitoshi , Higuchi Makoto 
Published: December 2023

AbstractBackgroundFrontotemporal dementia (FTD) is a group of neurodegenerative disorders with diverse clinical and neuropathological features. However, in vivo neuropathological assessments of FTD at an individual level have not hitherto been successful. Here, we aimed to classify patients with FTD based on topologies of tau protein aggregates captured by positron emission tomography (PET) with 18F‐florzolotau, which allows high‐contrast imaging of diverse tau fibrils in Alzheimer’s disease (AD) and non‐AD tauopathies.MethodTwenty‐six patients with FTD, consisting of 15 patients with behavioral variant FTD (bvFTD) and 11 patients with other FTD phenotypes, and 20 age‐ and gender‐matched healthy controls were studied. They underwent PET imaging of amyloid and tau depositions with 11C‐PiB and 18F‐florzolotau, respectively.ResultBy combining visual and semiquantitative analyses of PET images, the bvFTD patients were classified into the following subgroups: 1) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three‐repeat tauopathies (n = 3); 2) predominant tau accumulations in subcortical structures accompanied by various degrees of neocortical accumulations resembling four‐repeat tauopathies (n = 4); 3) amyloid and tau accumulations consistent with AD (n = 4); and 4) no overt amyloid and tau pathologies (n = 4). Despite these distinctions, clinical symptoms and localization of brain atrophy were not significantly different among the identified bvFTD subgroups. Patients with other FTD phenotypes were also classified into similar subgroups.ConclusionTo conclude, PET with 18F‐florzolotau potentially enables the characterization of each individual with FTD on a biological basis, thereby possibly contributing to diagnostic and therapeutic approaches to this illness.
Center of Alzheimer’s Disease in Beijing, China
Authors: Jia Jianping , Quan Meina 
Published: December 2023

AbstractInnovation Center of Neurological Disorders (ICND) at Xuanwu Hospital, Capital Medical University in Beijing was found in 2015 by Prof. Jianping Jia. The center follows the integrated research paradigm, called “cognitive unit”, which includes memory clinics, laboratories, and research wards. This unit facilitates the comprehensive diagnosis and treatment of cognitive disorders, and helps improve the quality of dementia research. There are 82 researchers, lab technicians and clinicians in the center, plus ∼20 graduate students and over 40 visiting/trainee doctors. We carry out research focusing on mechanisms, drug development and peripheral biomarkers of Alzheimer’s disease (AD) and related dementias. Our center leads several large national multicenter cohort studies, including the Chinese familial Alzheimer’s Network (CFAN), the China Cognition and Aging Study (China COAST), the Study on Biomarkers for Early Diagnosis of Alzheimer’s Disease (Bio‐AD), and the Dementia Cohort Project of “China Brain Initiative 2030”. Prof. Jia, the director of the center, is the PI of nearly 30 national and international multicenter clinical trials on drug development, and the 2021 recipient of the Zaven Khachaturian Award.The Center promotes multidisciplinary research on AD and related dementias. We collect extensive clinical data and biological samples, standardize the inclusion/exclusion criteria, establish large‐sample dataset and biobanks, provide advanced training for AD specialists, generate national guidelines on dementia management, train exchanging students and visiting scholars, and organize national and international dementia and Alzheimer’s conferences. Research findings from the center have impact on national health strategies, and help policymakers to establish public health strategies, and develop individualized and precision interventions. As an example, Prof. Jia established the large national Alzheimer patients cohorts to examine the genetic, biofluid, imaging and domain‐specific cognitive markers, and underling mechanisms. The Center encourages data sharing, exchanging ideas, and discussing possible solutions based on the mutual scientific questions and clinical problems, as well as the existing differences from each country.International Alzheimer’s Research Centers can collaborate on global initiatives for establishing international AD cohorts, screening tools and techniques to evaluate the diagnostic utility of biomarkers, and to initiate global multicenter clinical trials.
The contribution of school quality to stroke and cardiovascular disease risk in the U.S. Stroke Belt
Authors: Lybbert Emily , Muller Chandra , Grodsky Eric , Warren John Robert 
Published: December 2023

AbstractBackgroundStroke and cardiovascular disease (CVD) are important risk factors for later life dementia. In the United States the geographical distribution of high stroke risk, known as the U.S. Stroke Belt, is an important contributor to race and SES‐based gradients in not only CVD but dementia as well 1. In this study we examine the impact that schools have on stroke risk and CVD. We hypothesize that school characteristics will mitigate the effects of attending high school in a Stroke Belt state.MethodWe use the High School and Beyond study, a longitudinal dataset of individuals who were in high school in 1980. The most recent wave of data collection occurred in 2020/2021. We perform competing risk regressions to predict the hazard of dying from stroke and CVD controlling for going to high school in a Stroke Belt state, background characteristics, school quality, and individual education characteristics. We also predict the odds that surviving respondents had coronary heart disease or a stroke by 2021. Missing information on an individual level was multiply imputed and survey weights were used in all analyses.ResultHigh schools in the Stroke Belt had significantly lower average SES and students had lower achievement scores on average. Going to high school in a Stroke Belt state was associated with a higher hazard of early mortality due to cardio‐and cerebrovascular causes. Stroke Belt origin was also associated with higher odds of stroke diagnosis in midlife. These associations were partially accounted for by variation in background characteristics, especially parental education. Measures of school academic press were associated with cardio‐and cerebrovascular disease mortality and heart disease diagnosis, net of covariates.ConclusionThe findings of this study indicate that going to high school in the Stroke Belt is associated with higher risks of CVD and stroke. School quality seems to additionally affect individual risk, not explain the Stroke Belt risk.1. Glymour MM, Kosheleva A, Wadley VG, Weiss C, Manly JJ. Geographic Distribution of Dementia Mortality: Elevated Mortality Rates for Black and White Americans by Place of Birth. Alzheimer Disease & Associated Disorders. 2011;25:196‐202.
3D Bioprinted differentiated murine neurospheres as a neurogenesis model
Authors: Salles Geisa Rodrigues , Dall'Agnol Ferreira Natalia , Ferreira Clara Pompeu , Pacheco‐Soares Cristina , Porcionatto Marimelia Aparecida 
Published: December 2023

AbstractBackgroundAdult neurogenesis, the generation of neurons by neural stem cells (NSCs), occurs mainly in neurogenic niches, located in the dentate gyrus of the hippocampus and in the subventricular zone (SVZ) of the lateral ventricles. However, in Alzheimer’s disease (AD), proliferative activity of NSCs and the generation of new neurons is deregulated. Although there are animal models of AD, developing an in vitro three‐dimensional (3D) model of the disease may certainly enhance the approach of a multidinamic microenvironment able to evaluate specific areas of pathogenesis. The aim of this study was to produce 3D constructs targeting their application as an in vitro model of neurogenesis.MethodNeurosphere (clusters of NSCs and neural progenitor cells) cultures were developed from isolated cells from the SVZ of 6 weeks old C57bl/6 mice. Cells were cultivated in poly‐HEMA coated flasks for 7 days, then, formed neurospheres (∼100µm) were dissociated and bioprinted in an alginate:gelatin solution (6%:4%, respectively). The bioink was 3D printed, crosslinked with 2% CaCl2, and the constructs were maintained for 2 days in culture medium to allow neurosphere expansion. From days 3‐7, the constructs were cultivated in growth or differentiation medium, to stimulate neuronal differentiation. Morphological organization of cells within the neurospheres was evaluated.ResultThe produced 3D constructs are cytocompatible and allow neurosphere formation and growth under growth condition (Fig. 1A). As the growth medium was substituted by the neuronal differentiation medium, processes outgrowth was observed spreading outside the spheres (Fig. 1B).ConclusionA biocompatible construct loaded with neurospheres was produced by 3D bioprinting. The outgrowth of cellular processes outside the spheres suggest that neuronal differentiation occurs, showing that the biomaterial consists in an excellent model to investigate neurogenesis and neurogenic niches dynamics, two impaired elements in AD pathogenesis. Further steps of this study include the improvement of the 3D constructs, creating a microenvironment suitable to better simulate the potential of cellular differentiation under AD pathological conditions.
Acknowledgments: This study was supported by São Paulo Research Foundation (FAPESP, grants 2022/08664‐4 and 2018/45605‐8), and by the Brazilian National Council for Scientific and Technological Development (CNPq, grant 406258/2022‐8).
Metabolites correlate with plasma biomarkers and clinical diagnosis of Alzheimer’s Disease
Authors: Kalia Vrinda , Reyes‐Dumeyer Dolly , Dubey Saurabh , Nandakumar Renu , Lee Annie J , Lantigua Rafael A. , Medrano Martin , Mejia Diones Rivera , Recio Patricia , Honig Lawrence S. , Mayeux Richard , Miller Gary W , Vardarajan Badri N 
Published: December 2023

AbstractBackgroundEnergy, amino acid, and lipid metabolism are dysregulated in Alzheimer’s Disease. We investigated circulating plasma metabolites to capture systemic biochemical changes associated with Alzheimer’s disease (AD) using the clinical diagnosis and followed by the addition of plasma‐based biomarkers.MethodExogenous and endogenous metabolites in plasma were measured in 300 individuals with a clinical diagnosis of AD and 430 healthy individuals without dementia of Caribbean Hispanic ancestry using untargeted liquid‐chromatography, performed on HILIC (+ ionization) and C18 (‐ ionization) columns, coupled to a Thermo Orbitrap HF‐X mass spectrometer. Genome‐wide SNP data and plasma biomarkers including pTau181, Aβ40, Aβ42, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were obtained on all participants. Metabolite association with the clinical diagnosis of AD and for the AD biomarker, pTau‐181, levels were assessed after adjustment for age and sex.ResultMore than 6000 metabolic features were measured with high accuracy in the sample. 270 metabolic features were associated with pTau‐181 levels and 66 metabolic features were associated with clinical AD status, after correction for multiple testing. Valyl‐Serine (p = 1.1e‐7) and creatinine (p = 9.6e‐7) were strongly associated pTau‐181 levels. When using a diagnostic cutoff of pTau181 levels for AD as the outcome (biological AD), we also observed significant associations with a lysophospholipid (p = 9.5e‐5). Malic acid (p = 4.2e‐4) and tryptophan (p = 3.9e‐4) were significantly associated with clinical AD status. Metabolites associated with pTau‐181 levels were enriched in glycan biosynthesis, energy, amino acid, urea cycle/amino group and carbohydrate metabolism pathways. Patients with both clinical and biological AD showed altered tyrosine and tryptophan metabolism.ConclusionMetabolites, specifically amino acids and lipids, were associated with AD status and pTau181 levels. Metabolite profiling can identify perturbed pathways in clinical and pre‐clinical AD and integration with genome‐wide SNP data will identify mechanisms underlying genetic association with disease.