bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Signatures of Alzheimer’s Disease (AD) in SARS‐Cov‐2 Infected Mouse Brains
Authors: Parekh Parag A , Badachhape Andrew A , Menon Renuka , Ghaghada Ketan , Ronca Shannon E , Annapragada Ananth 
Published: December 2023

AbstractBackgroundCOVID‐19 is primarily a respiratory syndrome caused by SARS‐CoV‐2 infection, however, a third of COVID‐19 patients report post‐acute neurological sequelae. A close correlation between COVID‐19 and neurodegenerative diseases poses the question of viral etiology and its effect on pre‐existing disease. In this work, we performed brain transcriptomics to compare gene changes in SARS‐CoV‐infected mice and mouse models of Alzheimer’s disease (AD) pathology to investigate the relationship between neuroinflammation, immune response, and associated molecular signature of AD.MethodK18‐hACE2 transgenic mice (6‐8 weeks old) expressing human ACE2 receptor were intranasally infected with SARS‐COV‐2 virus (Ancestral USA/WA1/2020). Mock‐infected mice were used as controls. Animals were euthanized 5‐10 days post‐infection. Brains were harvested, treated for viral deactivation, and processed for mRNA extraction. Brains harvested from an uninfected APP/PS1 mouse model of amyloid pathology (9‐12 mo old) and P301S model of tau pathology (8‐9 mo old) were used for comparison. TopHat was used to align RNA‐Seq using Bowtie mapped to the current reference mouse genome assembly. Cufflinks was used to estimate the abundance of transcripts and test for differential expression and regulation.ResultAssessment of differentially expressed genes (p value <0.05) between SARS‐CoV‐2 infected and uninfected K18‐hACE2 brain samples were compared with RNA from uninfected mouse models of AD. The differentially expressed gene set identified 36 upregulated genes that include disrupted RNA metabolism genes, interferon‐ genes, TNF‐associated genes, ubiquitin‐associated genes, transporters, and enzymes. Downregulation of a single gene Tnfrsf17 that has also been reported in patients with severe Covid‐19 (Table 1) and AD patients was observed.ConclusionBrain transcriptomic profiling of SARS‐CoV‐2 infected mice revealed gene changes that are consistent with those in AD mouse models of amyloid and tau pathology. Our studies warrant further investigation of viral infections as a causative force of transcriptomic changes that precede neurodegeneration.
Teleconference group singing programs for well‐being of healthy older adults and persons with neurocognitive disorders during the COVID‐19 pandemic
Authors: Schafer Rhiana , Bonakdarpour Borna , Miller Sandra Siegel , Miller Jonathan 
Published: December 2023

AbstractBackgroundDuring the COVID‐19 pandemic, older adults experienced a marked decline in well‐being, attributed largely to social isolation (Tilburg et al, 2021; Krendl et al, 2021). Previous literature shows that participatory musical interventions, like group singing, improve well‐being and provide social and emotional support (Pentikäinen et al, 2021; Johnson et al, 2020). However, the pandemic highlighted the need for research on how such programs may be administered in an online setting. The enforced shutdown of in‐person choirs in 2021 provided an opportunity for such assessment.MethodTwo types of group choir programs were conducted via teleconferencing. One program engaged participants in sing‐along to familiar music only, offered weekly (52 in 2021). The other involved structured rehearsals (14 sessions) where participants learned choir music, culminating in a recorded "virtual concert”. Program participants were 55 and older, divided into persons with neurocognitive disorders (NcD) and cognitively healthy individuals (CH). Self‐report assessments of the programs were solicited. Four Likert scale questions covered anxiety, social connections, physical well‐being, and “other” areas of well‐being. Two free response questions requested elaboration on other well‐being improvement.ResultResults of Likert scales indicated at least moderate improvements in all measured aspects of well‐being. Feedback was overwhelmingly positive (>95%). Free response analysis revealed 7 themes, the most prominent being emotional, social, and intellectual well‐being. 87% of respondents mentioned positive effects on well‐being. Intellectual well‐being was mentioned with significant frequency by choir participants versus sing‐along (p = 0.02). While the NcD choir group was small, hampering statistical power, clear trends were present; 40% of participants in the NcD choir highlighted social well‐being (25‐29% in other groups), and 20% discussed improvements to physical well‐being (0‐6% in other groups).ConclusionOnline group music programs administered during the COVID‐19 pandemic showed improvements in overall measures of well‐being, with different programs and participants highlighting specific aspects. These results establish feasibility for such programs as a method for providing meaningful improvement to well‐being in older adults, providing stability and connection amidst a time of disruption and isolation.
Regional White Matter Hyperintensities are Associated with Diminished Blood Flow and Microstructure in Middle Age
Authors: Alshikho Mohamad J , Pyne Jeffrey , Lao Patrick J. , Turney Indira C , Berroa Joncarlos , Gutierrez Jose , Manly Jennifer J. , Brickman Adam M. 
Published: December 2023

AbstractBackgroundWhite matter hyperintensities (WMH) are areas of increased signal visualized on T2‐weighted FLAIR magnetic resonance imaging (MRI), thought to reflect macrostructural damage due to small vessel cerebrovascular disease. Previous work established an association of WMH severity, particularly in posterior regions, with risk and progression of AD in late onset and genetic forms of AD, suggesting a vascular component to disease pathogenesis and course. Examination of the emergence and correlates of cerebrovascular changes in middle age, a critical time when vascular risk appears to be most penetrant, can give insight into mechanisms linking vascular brain injury and risk for AD. In the current study, we examined the association of cerebral blood flow (CBF) and white matter microstructure with total and regional WMH volume in middle‐aged, community dwelling adults.MethodFour hundred and ninety‐two middle‐aged participants (55+/‐11 age = 28 ‐85 years) from the community‐based Offspring Study of Mechanisms for Racial Disparities in Alzheimer’s Disease received multi‐modal MRI scanning. Regional WMH volumes were derived with in‐house software that labeled clusters of voxels within a hyperintense intensity distribution. Pulsed arterial spin labeling (PASL) sequences were processed to quantify CBF. Fractional anisotropy (FA) maps were obtained from diffusion weighted data. Total and regional WMH volumes were used as predictors for whole brain voxel‐wise correlation analyses in separate models for CBF and FA.ResultThere were negative associations between WMH volume and CBF in frontal, parietal, and occipital regions. Higher white matter hyperintensity volume was associated with lower FA, particularly in the periventricular region.ConclusionWe found associations of increased WMH volume with diminished blood flow and white matter microstructure. Future studies are needed to explain the relationship between these changes and the risk of cognitive impairment in middle aged adults and risk for AD.
Caregivers and non‐caregivers attitudes regarding pre‐symptomatic Alzheimer’s disease testing
Authors: Makri Marina , Despoti Akylina , Gkioka Mara , Tsolaki Magda 
Published: December 2023

AbstractBackgroundOver the past decade there has been increasing testing of biomarkers and new methods of presymptomatic screening for Alzheimer disease (AD). But still, there is little known about the beliefs of patients and family caregivers regarding testing in Greece. The aim of this study is to assess the attitudes, barriers and motivations to pre‐symptomatic AD testing, among older adults with and without an experience of AD caregiving.MethodA total sample of 213 participants (Caregivers, N = 96 and Non‐Caregivers, N = 117) answered the ‘’Perceptions regarding pre‐symptomatic dementia testing” (Pre‐dem) questionnaire. Most participants were females (N = 179) and were 41‐50 (N = 56) and 51‐60 (N = 55) years old.ResultA two‐sample t‐test was performed to compare the four domains in caregivers and non‐caregivers and there was no significant difference, and also compare with and without a family history of AD and there was not a significant difference in perceived harms of testing, perceived benefits of testing, and need of knowledge. There was a significant difference in acceptance of testing between participants with a history of AD (M = 4.67, SD = 3.86) and non‐history (M = 6.83, SD = 4.33); t(211) = ‐3.75, p = 0.00. A one‐way ANOVA was conducted to compare the four domains with the years of care (1‐3, 3‐5, and more than 5 years). There were no significant differences between the domains and the years of care. Finally, a one‐way ANOVA was conducted to compare the four domains with the age of the first diagnosis of the relative or friend of the caregiver (51‐55, 56‐60, 61‐65, 66‐70 and 70+). There were no significant differences between the domains and the age that the relative/friend was diagnosed.ConclusionThis is the first study that assessed the attitudes towards dementia and genetic screening of Greek older adults with and without an experience of dementia caregiving. Both participants had similar beliefs regarding the pre‐symptomatic dementia testing, except for the acceptance of testing in participants with and without a family history of AD. There is a need for more information, education and empowerment of the caregivers regarding dementia screening but also the general public.
Experience in a primary care inpatient hospital (Comárcal) with the use of CSF results for the diferential diagnosis of Alzheimer’s disease
Authors: Oliveros‐Cid Antonio , Hojas Sarai Garcia , Agreda Delia Quilez , Obanos Maria Teresa Rubio , Oliveros‐Juste Antonio , Cimorra Belen Delgado , Carrasco Ana Chacon , Catalan Claudia Ovejas , Echeverria Aitziber Echeverria , Lopez Maria Angeles Cid , Moreno Lisbed Rondon , Salvador Fernando Jarauta 
Published: December 2023

AbstractBackgroundTo analyze the usefulness of the use of Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (CSF) since its incorporation into clinical practice, in a first‐line care hospital setting.MethodWe review clinical history, neuroimaging and neuropsychology, and results of B‐amyloid 42, B‐amyloid 42/40 ratio, total tau and p‐tau in CSF in patients who consulted for cognitive impairment. Prior to biomarker determination, they were assigned a degree of suspicion based on history, neuroimaging and neuropsychology. Afterwards, they were reclassified into probable AD/ dementia not AD/no evidence of AD or neurodegeneration according to the ATN system. Finally, the usefulness was assessed according to whether a high degree of diagnostic certainty was achieved in each case.Result39 patients gave ICF and were analyzed; mean age 69.5 years; cases with typical and atypical clinical course. After determination of biomarkers, they were classified according to whether they presented A+/A‐, T+/T‐ and N+/N‐; findings were correlated with previous clinical and paraclinical data and compared with them, and stratified according to the degree of diagnostic certainty provided. A high degree of diagnostic certainty was achieved in 34/39 patients.Conclusiondetermination of CSF biomarkers is a useful, affordable and decisive tool in the differential diagnosis of patients with Alzheimer’s disease, which makes it a diagnostic resource to be used preferably even in primary health care hospitals.
Mild excitotoxic effect on mitochondrial membrane potential, Ca2+ homeostasis and energy production in a mouse model of Alzheimer’s disease
Authors: Basso Emy 
Published: December 2023

AbstractBackgroundNeurons are bound to maintain a tight control over their cellular homeostasis in order to preserve their many functions, and specifically to precisely regulate ion fluxes for the generation of action potential and neurotransmission. In particular, the energetic balance has to be finely adjusted since its alteration may hamper cellular functionality with consequent cell suffering and death. Mitochondria play a central role in the homeostatic regulation within the cells due to the many vital tasks they perform in terms of energy production, participation in the regulation of Ca2+ concentration, modulation of intracellular signaling that allow the cell to respond to external solicitationMethodPrimary hippocampal neuronal cultures of 14‐17 DIV from WT and AD mouse model were challenged with μM concentration of glutamate to induce a mild excitotoxic effect; mitochondrial membrane potential, mitochondrial an cytosolic Ca2+ transients and cytosolic ATP levels were evaluated with fluorescent probes. Cells were treated also with inhibitors of the permeability transition pore to evaluate its effect on cell functionalityResultWe observed that in a model of Familial Alzheimer’s disease, hippocampal neurons are sensitive to a modest excitotoxic signal that produces a transient cytosolic and mitochondrial matrix Ca2+ with consequent partial loss of mitochondrial membrane potential and delayed recovery of mitochondrial matrix [Ca2+] which might contribute in the activation of the mitochondria permeability transition pore and consequent impairment of mitochondrial and cellular functions. This is accompanied by a reduced cytosolic ATP content that can result in an energy deficit for the cell. A brief treatment with inhibitors of the permeability transition pore is able to reduce these effects and might have protective roles against exogenous insults to the cells and help mitigate the neuronal loss characteristic of Alzheimer’s disease.ConclusionAD hippocampal neurons are more sensitive to a mild excitotoxic insult that affect mitochondrial functionality and in particular the activation of the permeability transition pore (PTP). Treatment with μM concentrations of two different inhibitors of the PTP prevent mitochondrial impairment.
Functional Connectivity of Entorhinal Cortex Predicts Tau in the Elderly
Authors: Nayak Siddharth , Hojjati Seyed Hani , Feiz Farnia , Ozoria Sindy , Shteingart Jacob , Picha Saman Gholipour , Fernández Antonio , Stern Yaakov , Devanand Davangere P. , Luchsinger Jose A , Razlighi Qolamreza R 
Published: December 2023

AbstractBackgroundHuman neuroimaging efforts to understand the pathophysiology of Alzheimer’s disease (AD) have solely focused on the amyloid‐beta (Aβ) deposition and tau neurofibrillary tangle formation. Until recently, the idea of a connectivity‐based molecular functional framework for understanding AD pathophysiology was missing, which eluded researchers from connecting functional connectivity (FC) with Aβ/Tau deposition.MethodThe initial dataset includes 631 older (67.44 ± 6.48 years) adults (521 healthy controls and 110 mild cognitive impairment (MCI)) who have been imaged for Tau pathology as well as resting‐state functional magnetic resonance imaging (rsfMRI) and structural MRI scans. Using Schaefer’s 200 parcellation atlas and a regional cutoff (SUVR = 1.25), we identified four groups of tau staging based on the number of regions having higher than cutoff tau SUVR (no tau stage (N = 193), pre‐acceleration stage (N = 222), acceleration stage (N = 149), and post‐acceleration stage (N = 67)). Since the entorhinal cortex (EC) is widely regarded as the epi‐center for tau accumulation, the left and right EC time series were derived from rsfMRI data using the Desikan‐Killiany atlas and used as seed regions for our Pearson correlation coefficient based functional connectivity analysis with all 200 regions in the Schaefer atlas. Finally, linear regression models were run to predict the mean regional accumulation of tau based on the strength of mean FC between that region and EC.ResultAs shown in Fig. 1, left/right EC functional connectivity is strongly associated with the accumulation of tau in that region during the pre‐acceleration phase (left: t = 3.586, p < 0.0004; right: t = 4.404, p < 0.0001) and in the acceleration phase (left: t = 6.229, p < 0.0001; right: t = 7.577, p < 0.0001) (results not shown). The functional connectivity values from left/right EC for the pre‐acceleration phase are plotted on the surface of the brain, as shown in Fig. 2.ConclusionOur results provide evidence of the role of functional connectivity in tau spreading from EC to the rest of the brain and can help throw light on the dynamic patterns of tau spreading in MCI/AD subjects in different disease stages.
24‐hour rest‐activity rhythms and light exposure patterns in relation to cognitive function in a nationally representative U.S. sample
Authors: Xiao Qian , Yeung Ho Ching , Lu Jiachen , Bauer Cici 
Published: December 2023

AbstractBackgroundHuman diurnal behaviors are orchestrated by the internal circadian clock and influenced by external stimuli such as light. Aging is associated with declined circadian output and shifted circadian phase, leading to weakened rest‐activity rhythms and altered light exposure patterns, which may in turn further exacerbate circadian impairment. Limited but growing research reported that characteristics of rest‐activity rhythms were associated with risk of dementia and cognitive decline in older populations. However, there are several gaps in the literature: 1) most previous studies included predominantly white participants with relatively high socioeconomic status, limiting the generalizability of study findings to more diverse populations; 2) few studies examined the 24‐hour light exposure pattern, an environmental cue essential to healthy circadian function, in relation to cognitive function.MethodsWe applied the extended cosine model, nonparametric algorithms, and functional principal component analysis (fPCA), to characterize rest‐activity rhythms and light exposure patterns in the National Health and Nutrition Examination Survey (2011‐2014). Cognitive function was measured by word learning and recall modules from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD), the Animal Fluency test, and the Digit Symbol Substitution test.ResultsMultiple rest‐activity characteristics were associated with different aspects of cognitive function, generally supporting a relationship between weakened circadian rhythms and poorer cognitive performance. For example, when compared to the highest quintile, the lowest quintile of F statistic, a measure of overall rhythmicity, was associated with a significantly lower score on the CERAD delay recall test (beta (95% confidence interval (CI)), ‐0.61 (‐0.77, ‐0.18)) and an increase in the odds of having a performance score in the lowest quartile of the study sample (odds ratio (95% CI), 1.55 (1.05, 2.29)). Moreover, measures of amplitude and rhythm fragmentation derived from nonparametric algorithms and fPCA were also associated with cognitive function. Findings were generally consistent across subgroups with different gender, age, race/ethnicity and education levels, but subgroup differences were also observed. Moreover, preliminary findings suggested a relationship between light exposure patterns and cognitive function.Conclusions24‐hour rest‐activity and light exposure patterns are associated with cognitive function in a diverse and nationally representative sample.
Socioeconomic determinants of cognition among older Brazilian adults: A life‐course approach
Authors: RAMOS ARI ALEX 
Published: December 2023

AbstractBackgroundThe prevalence of cognitive impairment is higher in low‐ and middle‐income countries compared to high‐income economies. Yet few nationally representative studies from Latin America have investigated life‐course socioeconomic factors related to the susceptibility to age‐associated cognitive impairment. In this study, we examined the associations of early‐ (education and food insecurity), mid‐ (employment stability), and late‐life (any personal income, household per capita income, and self‐perceived income) socioeconomic indicators with the risk of cognitive impairment, while simultaneously exploring whether gender plays an effect‐modifier role on these associations.MethodThe study population comprised Brazilian adults aged 50 years and over (N = 8710) from the Brazilian Longitudinal Study of Aging. Those with ≤ 1.5 SD on a global composite measure of cognition (N = 1005) were assigned to the cognitive impairment group. Unadjusted and mutually adjusted logistic regressions estimated odds ratios with 95% confidence intervals.ResultHigher midlife employment stability and late‐life household per capita income were positively associated with the health of adult cognition. Moreover, secondary analyses performed separately for males and females showed the higher the early‐life educational attainment, the lower the likelihood of impaired cognition among females but not among males. Conversely, having a source of income in old age showed a buffering role against cognitive impairment in males, but this association was not observed in females. No significant associations were noted for early‐life food insecurity or late‐life self‐perceived income.ConclusionThese findings may have implications for population health and health policy by advancing our understanding of socioeconomic determinants of mid‐to‐late‐adulthood cognition.
Plasma cell‐free RNA: a new non‐invasive biomarker for Parkinson’s disease
Authors: Beric Aleksandra , Cisterna‐García Alejandro , Chen Hsiang‐Han , Cruchaga Carlos , Ibanez Laura 
Published: December 2023

AbstractBackgroundParkinson’s disease (PD) is the second‐most common neurodegenerative disorder, after Alzheimer disease (AD). We aimed to create a model that can predict PD with high accuracy and specificity using plasma cell‐free RNA (cfRNA) data.MethodWe extracted RNA from 172 plasma samples (92 PD cases and 80 controls; 48% female, and median age of 73) received from the Hope Center for Neurological Disorders at Washington University in Saint Louis. After library preparation, sequencing, processing, and stringent quality control data was split into training (60%) and testing (40%) populations, both of which included 53% PD cases, 48% female, and had median age of 73. We then performed differential expression analyses using DESeq2, adjusting the by age, sex, medication and other technical variables. Following data driven identification of informative transcripts using Lasso regression, we used Ridge regression to model disease status.ResultWe identified and replicated 639 significantly dysregulated genes. Through pathway analyses we found that dysregulated genes were enriched in PD terms, as well as other neurodegenerative and in known mitochondria pathways. After predictive model training, the best model for PD in the testing population included 14 genes and had an Area Under the Receiving Operating Curve (AUC) of 0.963 (0.930, 0.996). The model had low predictive power, with AUC of 0.553 (0.421, 0.686), in differentiating between controls and AD, FTD or DLB, suggesting that it is specific to PD. More evidence of its specificity was the good performance in distinguishing between PD and AD, FTD or DLB with AUC of 0.753 (0.674, 0.833) specificity.ConclusionPlasma cfRNA is a powerful tool for PD prediction, being a minimally invasive biomarker that could detect PD before onset of physical symptoms and without relying on imaging data. We are working on replicating our results in an independent dataset.