bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating Cell Diversity and Functions of Human Brain Borders in Alzheimer’s Disease
Authors: Kearns Nicola , Iatrou Artemis , Avey Denis , Yu Chunjiang , Philippe Tristan , Flood Daniel , De Tissera Sashini L , Mullaney Zachary , Xu Jishu , Gaiteri Chris , Bennett David A. A , Wang Yanling 
Published: December 2023

AbstractBackgroundEmerging evidence shows that the brain border regions act as a functional neuro‐immune interface to conduct essential immune surveillance and immune defense1. The dysfunction of border immunity contributes to aging, microglial inflammatory response, and neurodegeneration2‐3.MethodWe conducted single nuclei multiome to simultaneously profile gene expression and open chromatin of dissected postmortem human brain borders from aged individuals with and without Alzheimer’s Disease (AD) (n = 32). We further generated border cell models from iPSCs and postmortem leptomeningeal cells to understand the effects of genetic and environmental factors on border cells.ResultWe detect diverse cell types at the brain borders, including unique endothelial, mural, immune, and fibroblast subtypes. Border‐associated macrophages (BAMs) display differential gene expressions from microglia and express AD risk genes, as nominated by genome‐wide association studies (GWAS). We discover cell‐type‐specific differentially expressed genes in AD individuals, particularly fibroblasts and BAMs. We identify gene regulatory networks and master regulators of specific border cell states. Human cell models of leptomeningeal cells display the signature of ex vivo AD fibroblasts upon amyloid‐β treatment, and iPSC‐derived choroid plexus models carrying the APOE4 risk alleles demonstrate differentially expressed genes related to immune and fibrotic response. Lastly, we explore ligand‐receptor interactions within the border niche and observe increased intercellular activities and altered communication patterns at AD brain borders.ConclusionOur study establishes a molecular map of human border cell types and reveals the functional effects of AD risk factors on brain border cells, providing significant insight into the border immune and fibrotic responses in AD pathogenesis.References:1. Alves de Lima, K., Rustenhoven, J. & Kipnis, J. Meningeal Immunity and Its Function in Maintenance of the Central Nervous System in Health and Disease. Annu. Rev. Immunol. 38, 597‐620 (2020).2. Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 560, 185‐191 (2018).3. Da Mesquita, S. et al. Meningeal lymphatics affect microglia responses and anti‐Aβ immunotherapy. Nature 593, 255‐260 (2021).
Posterior Primary Progressive Prosopagnosia: Imaging and Neuropathology
Authors: Appleton Johanna , Bradbury Kathleen , Shyer Madison , Finn Quentin , Arbones Victoria , Dickerson Brad C. , Cykowski Matthew D , Masdeu Joseph C. , Pascual Belen 
Published: December 2023

AbstractBackgroundProsopagnosia is common with right temporal lesions, often in the fusiform gyrus when caused by vascular pathology. When caused by frontotemporal dementia, the lesion typically begins in the temporal tip. We are reporting advanced imaging, including tau and inflammation, as well as neuropathology in a patient with pathology centered at the posterior extent of the fusiform gyrus.MethodA 69‐year‐old man with apperceptive prosopagnosia and a negative amyloid positron emission tomogram (PET) underwent MRI and PET using 11C‐PBR28, an inflammation tracer, and 18F‐flortaucipir. V
T values for 11C‐PBR28 were calculated with the Logan plot and a metabolite‐corrected arterial input function. For 18F‐flortaucipir, the SUV ratio over the cerebellar gray matter was calculated for t = 80‐100 min. A neuropathological examination was conducted using standard procedures as well as phospho‐tau histochemistry.ResultAtrophy and 18F‐flortaucipir uptake involved a similar region at the posterior extent of the right fusiform gyrus and, minimally, a symmetrical region of the left fusiform gyrus and an area in right premotor cortex. Involving the same regions, the 11C‐PBR28 signal was however more extensive than atrophy or 18F‐flortaucipir signal. At autopsy, the patient had corticobasal degeneration (CBD), with severe 4R tau involvement of temporo‐occipital, inferior parietal, and frontal cortices, as well as limbic regions and subcortical nuclei. The location of CBD pathology in this patient was highly atypical, as shown by comparing the neuropathological findings with the findings in two typical CBD patients.ConclusionAlthough prosopagnosia from ischemic and other lesions in the right posterior temporo‐occipital region is common, primary progressive prosopagnosia in the absence of amyloid has been described mostly with involvement of the right anterior temporal region. As exemplified by our patient, it can rarely happen with posterior temporal involvement and in this case the pathology was not TDP‐43 type C, as present in most patients with anterior temporal involvement, but corticobasal degeneration, a 4R tauopathy.
Mapping the effects of functional and structural network reorganization on the tau‐cognition relationship in Alzheimer’s disease
Authors: Ottoy Julie , Kang Min Su , de Wael Reinder Vos , Park Bo‐Yong , Bezgin Gleb , Lussier Firoza Z , Rahmouni Nesrine , Stevenson Jenna , Arias Jaime Fernandez , Soucy Jean‐Paul , Gauthier Serge , Bernhardt Boris , Black Sandra E. , Rosa‐Neto Pedro , Goubran Maged 
Published: December 2023

AbstractBackgroundTau pathology can spread through connectivity‐based networks, with certain regions (or epicenters) accumulating more tau than others. Such spatial vulnerabilities may be due to their unique apical position in the cortical hierarchy, which can be elucidated through ‘gradients of connectivity’ (Margulies 2016 PNAS). Prior work showed that the primary gradient of functional connectivity unveils a uni‐to‐transmodal topography of the healthy neocortex which highly correlates with a cognitive gradient of perception‐to‐abstraction. Here, we hypothesized that the gradients of functional/structural connectivity interact with tau to affect cognitive functions in Alzheimer’s disease (AD).MethodWe included 213 participants from TRIAD (103 CN Aβ‐, 103 CN Aβ+, and 75 CI Aβ+) with diffusion‐weighted MRI, resting‐state functional MRI, 18F‐MK6240 tau‐PET, and an extensive cognitive battery. We performed non‐linear dimensionality reduction on the individual functional and structural connectomes, and extracted the first components (‘gradients’) ‐explaining most variance (G1FC and G1SC). First, we compared G1FC_or_SC between diagnostic groups. Second, we investigated the interaction effect of G1FC_or_SC*tauSUVR on cognition (across 9 cognitive domains). Last, we investigated whether the tau‐cognition relationship changed in a topography‐specific manner along the cortical hierarchy, within (equally‐sized) gradient‐derived meta‐ROIs along G1FC_or_SC. Results were compared to Braak‐derived regional associations. Analyses were adjusted for age, sex, APOE, education, and multiple comparisons.ResultWe observed reduced segregation of functional networks in AD compared to controls, with unimodal (lower‐order cognitive) and transmodal (higher‐order cognitive) regions moving closer on G1FC. This may indicate loss of network specialization in AD. Participants who had both higher tau and G1FC alterations had more cognitive impairment (Fig.1A; shown for MMSE/language). This interaction‐effect was less pronounced with G1SC (Fig.1B). Last, tau correlated with cognition in a topography‐specific progressive manner (i.e., along the transmodal‐unimodal G1FC axis and anterior‐posterior G1SC axis) (Fig.1C). Notably, tau correlated with delayed memory progressively along the posterior‐anterior G1SC axis (R2 = 0.93 in all and R2 = 0.95 in A+) and BraakI‐VI axis (R2 = 0.77 in all and R2 = 0.28 in A+).ConclusionOur work supports the contribution of connectome‐driven tau distribution on cognitive impairment in AD. Connectome gradients may provide a spatial framework to study tau spreading along the major axes of brain organization underlying specific cognitive domains.
Blood pressure variability and functional network connectivity in older adults
Authors: Sible Isabel J , Jang Jung Yun , Blanken Anna E , Alitin John Paul M , Dutt Shubir , Marshall Anisa J , Kapoor Arunima , Shenasa Fatemah , Engstrom Allie , Gaubert Aimee , Nguyen Amy , Mather Mara , Nation Daniel A. 
Published: December 2023

AbstractBackgroundBlood pressure variability is an emerging risk indicator for cerebrovascular disease and Alzheimer’s disease, independent of traditionally studied mean blood pressure levels. Recent studies suggest elevated blood pressure variability in older adults is also associated with attenuated cerebrovascular reactivity, which may have implications for functional hyperemia underpinning brain network connectivity. However, it remains unclear whether blood pressure variability is related to functional network connectivity. We examined relationships between beat‐to‐beat blood pressure variability in older adults and functional connectivity in multiple brain networks vulnerable to Alzheimer’s disease and related disorders (AD/ADRD).Method32 community‐dwelling older adults (mean [SD] age = 69.6 [7.5] years) without history of dementia or clinical stroke underwent continuous blood pressure monitoring during a 5‐minute period of rest and resting state fMRI. Blood pressure variability was calculated as variability independent of mean, an increasingly used index of variability uncorrelated with mean blood pressure levels. Functional connectivity was determined by resting state fMRI for several brain networks: default mode, salience, dorsal attention, fronto‐parietal, and language. Multiple linear regression examined relationships between blood pressure variability and functional network connectivity, controlling for age, sex, and mean blood pressure. Associations with mean blood pressure were also explored to directly compare potential effects with blood pressure variability.ResultElevated blood pressure variability was associated with lower functional connectivity in the default mode network (ß = ‐.55 [‐1.02, ‐.08]; p = .02). There were no significant associations between blood pressure variability and connectivity in other functional networks (p’s = .10 ‐ .62). Mean blood pressure was not related to functional connectivity in any network (p’s = .08 ‐ .98).ConclusionOlder adults with elevated blood pressure variability exhibit resting state functional connectivity deficits in the default mode network. Findings add to literature supporting the role of blood pressure variability in neurovascular dysfunction and AD/ADRD. Blood pressure variability may represent an important but understudied early vascular risk factor for neurovascular dysfunction relevant to AD/ADRD, with potential therapeutic implications.
Analysis of brain functions in the older adults: A Systematic Review on functional near‐infrared spectroscopy
Authors: Kim Mi Kyeong , Lee Hamin , Yun Sohyeon , An Hyun Seo , Kim Inhye , Park Hae Yean 
Published: December 2023

AbstractBackgroundAs the aging phenomenon accelerates worldwide, cognitive health and improvement of the older adults are emerging as important issues. This study was conducted to obtain implications for future clinical and research directions related to elderly cognition by examining studies that identified the brain function of the elderly using brain activation or functional connectivity.MethodThree databases(Web of Science, Scopus, Pubmed) were used to collect literature for a total of five years from January 2018 to December 2022. Using “(“older adult*” OR “elderly”) AND “fNIRS” AND (“functional activation” OR “functional connectivity”)” as the search term, we selected and analyzed the final 8 literature that matched the selection criteria and exclusion criteria of this study.ResultThere were 5 cases targeting healthy older adults and 3 cases for the older adults with mild cognitive impairment, and the most active study in China was shown. In addition, a total of six types of NIRS systems were used to explore brain function in the elderly, and five studies confirmed that the NIRS system produced in Japan was used. In the case of the number of channels used, it had a wide range of 14 to 48, and there were only two studies showing functional connectivity.ConclusionThis study confirmed that it is possible to identify the cognitive function of the older adults using fNIRS, and at the same time, few studies have measured functional connectivity. Since brain regions do not work independently, it is essential to understand functional connectivity that identifies functional integration between brain regions that share similar functions, even if they are located apart. Therefore, based on the results of this study, it is believed that a better understanding of functional brain changes can be achieved if brain activation and functional connectivity are also identified when conducting cognitive‐related research in the elderly using fNIRS in the future.
Dementia Caregiver Burden associated with COVID‐19 quarantine: A South American Cohort Study
Authors: Arruabarrena Micaela Maria , Fernández Rodrigo S , Martinez Carlos , Corvalan Nicolas , Keller Greta , Sevlever Gustavo , Allegri Ricardo Francisco , Crivelli Lucía 
Published: December 2023

AbstractBackgroundIn December 2019, a new virus, Coronavirus disease (COVID‐19/SARS‐CoV‐2), burst into the world. Social distancing reduces its transmission and delays the spread peak. However, because of the late arrival of vaccines to our region, Argentina had a rigorous mandatory preventive social isolation (MPSI) policy that extended beyond global record. As a result, MPSI had a disruptive impact on the actions associated with the well‐being of dementia patients, and caregivers. In addition, MPSI added to the well‐known caregiver burden already present in many dementia patients’ caregivers. This study aims to investigate the impact of MPSI on dementia patients’ caregivers’ mental health and to identify predictors of caregivers’ burden.MethodA sample of 112 caregivers (75.89% female; age 58.65 ± 14.30) of patients with dementia answered a survey with the following questionnaires: Zarit Burden Interview (ZBI), Weekly hourly load dedicated to dementia care, time spent on leisure activities (activity diary provided by Argentine National Institute of Statistics and Census), the Caregiver Activities Survey (CAS) and the Depression, Anxiety and Stress Scale (DASS‐21). These questionnaires evaluate caregiving characteristics and their impact on the caregiver. Additionally, history of COVID‐19 was recorded for patients, caregivers and people living with either of them.ResultMost caregivers were women (75.89%). This difference hindered direct comparison between men and women. A regularized L2 regression was performed and the number of caregiving hours (β = 0.090), depression (β = 0.085), anxiety (β = 0.099), stress (β = 0.164), and fear of COVID‐19 (β = 0.141), were identified as predictors of caregiver burden. Finally, a mediation analysis was also performed, and hours of care (CAS; r = 0.254), being the primary caregiver, and fear of COVID‐19 (r = 0.335) were identified as mediators of the effect between anxiety, depression, stress (DASS) and burden (ZBI).ConclusionCaregivers of dementia patients show sequelaes of anxiety, stress, depression, and caregivers’ burden in the context of COVID‐19 spread and during MPSI. Being a primary caregiver, dedicating more hours to caregiving, and fear of COVID‐19 are factors that contribute significantly to caregiver burden and mediate between this burden and mood variables. Relief of caregivers' burden could be aided by the design of public health policies that specifically address the mediators identified in this study.
Race, inflammation, and amyloid deposition in Black/African American and Non‐Hispanic White older adults
Authors: Stradford Joy , Snitz Beth E. , Becker James T , Roush Rebecca E. , Reese Alexandria C. , Lopresti Brian J , Cisneros Geraldine , Potopenko Katey , Lopez Oscar L. , Cohen Ann D. , Pa Judy 
Published: December 2023

AbstractBackgroundBlack/African American (AA) older adults are twice as likely as Non‐Hispanic White (NHW) older adults to be diagnosed with Alzheimer’s Disease (AD) and related dementias. Inflammation and brain beta‐amyloid (Ab) may play a differential role in AD pathophysiology in AA and NHW older adults. We hypothesized that there would be racialized group differences in inflammation, amyloid deposition, and everyday discrimination.MethodOne hundred and ninety‐eight participants (Table 1) were recruited in Pittsburgh, PA and the surrounding areas as a part of the Human Connectome Project. Blood‐based biomarkers of inflammatory markers interleukin 6 (IL6) and tumor necrosis factor alpha (TNFa) were examined. Brain Ab was quantified using Pittsburgh Compound‐B (PiB) Positron Emission Tomography (PET) imaging standardized uptake value ratio (SUVr). Experiences of discrimination were measured on a subset of 66 participants (mean age = 62.62±9.37 years, 46.97% AA) using the Everyday Discrimination Scale (EDS). Analysis of covariance, controlling for age, were conducted to examine the racialized group differences for TNFa, IL6, Ab SUVr. Independent samples t‐tests were conducted to compare EDS by racialized group.ResultParticipants. AA participants were on average 6.58 years younger than NHW participants and more likely to have a clinical diagnosis of impaired without complaints, mild cognitive impairment (MCI), or AD (all p’s<.05) (Table 1). Additionally, in the subset of participants with EDS data, AA participants experienced higher total discrimination than NHW participants (p<.05).Inflammation. NHW participants had higher TNFa inflammation levels than AA participants (p = .029). No differences by racialized group were observed for IL6.PiB‐PET. The frequency of amyloid positivity was higher in NHW than AA participants (p = <.001). Global Ab SUVr was higher in NHW than AA participants (p<.05).ConclusionThe results from this study provide evidence of higher peripheral blood inflammation and PiB PET binding in NHW than AA participants, but higher likelihood of clinical diagnoses and more experiences of discrimination in the AA than in NHW participants. Future investigation of these racialized differences as they relate to age and other determinants of health are needed.
Associations Between Cardiovascular Risk Factors and Arterial Spin Labelling Derived Perfusion Parameters
Authors: Tee Mervin , Padrela Beatriz E. , Konstandin Simon , Eickel Klaus , Günther Matthias , Petr Jan , Mutsaerts Henk‐Jan , Hilal Saima 
Published: December 2023

AbstractBackgroundDecreased cerebral blood flow (CBF) and deterioration of blood‐brain barrier (BBB) are suggested to be precursor conditions of cognitive impairment. Using a novel multi‐echo‐time arterial spin labelling (ASL) protocol, we examined the time of exchange (Tex) of water across the BBB as a measurement of BBB permeability. We further examined the association of cardiovascular risk factors with Tex in an ongoing cohort study.MethodData (n = 29, mean age: 55.9±6.1years, 69% women) were drawn from Neurological biomarkers of Blood, MRI and Cognition (NEURO‐BMC) study performed at National University of Singapore. NEURO‐BMC is an ongoing prospective cohort study (age: 45‐65 years) on brain changes in a subclinical phase of cognitive impairment. A multi‐echo, Hadamard‐encoded multi‐post‐labelling‐delay pseudo‐continuous ASL (PCASL) protocol was used on a 3T scanner. ExploreASL was used with a modified version of FSL FABBER(4) to quantify cerebral blood flow (CBF), arterial transit time (ATT), and Tex. ASL‐extracted parameters were compared with cardiovascular risk parameters such as blood pressure (BP), BMI and smoking status.ResultHigh systolic and diastolic BP were associated with significantly reduced Tex (Fig 1). Additionally, higher systolic and diastolic BP showed a trend of increased ATT and reduced CBF, though the associations were not statistically significant (Table 1). High BMI had a significant association with increased ATT and reduced CBF. However, no trend was observed between BMI and Tex. Participants who ever smoked were observed to have a reduced Tex and CBF and increased ATT, but statistical significance was only found for CBF (Fig 1).ConclusionIn this pilot study, we showed that BBB‐ASL‐derived parameters ‐ ATT, CBF, and Tex ‐ were associated with BP, BMI, and smoking status. While the sample size for this preliminary analysis was too small to make a definitive conclusion as not all associations were statistically significant, all studied cardiovascular risk factors showed their potential in increasing the risk of BBB deterioration. Further investigation with a larger sample size and other health risk factors to assess these observations is warranted.
Dementia Research Policy and Infrastructure in Costa Rica as a Central American Upper‐Middle Income Country
Authors: Josephy‐Hernandez Sylvia E. , Pérez‐Rojas Randall , Acosta‐Egea Sabrina , Miranda‐Valverde Erick , Román Norbel , Steele Hector Anthony , Aguilar Daniel Valerio , Leon‐Salas Jorge M 
Published: December 2023

AbstractBackgroundClinical research in Costa Rica came to a halt in 2010 when the legislative assembly, due to concerns around lack of oversight, declared that no studies could continue until research involving human beings was regulated by law. Legislation did not come to pass until 2014. Currently, clinical research is performed within both the public and private healthcare systems. With this study, we aim to showcase the growth of research in dementia in Costa Rica since 2014 and explore gaps that remain.MethodWe performed a bibliographic search for dementia research in Costa Rica, both in English and in Spanish. Search engines included PubMed, PMC, and Google Scholar. We also collaborated with clinicians and researchers from private and public institutes to delineate the current research network.ResultWe extracted 60 publications; 90% of the articles were published after 2014, with the largest increase after 2019 (63% of publications). 60% of publications derived from international collaborations. We identified 89 Costa Rican researchers authoring these publications, with 82% of authors belonging to the public sector. Two main public universities (University of Costa Rica and National University) and two main public hospitals (National Geriatrics Hospital and San Juan de Dios Hospital) produced most of the data. Important international collaborations including LatAm Fingers are taking place with one private hospital (Clínica Bíblica Hospital). An aspirational international collaboration is the inclusion of Costa Rica in ReDLat.ConclusionThere has been an exponential growth of research in dementia in Costa Rica since 2014, reflected in the highest growth of publications after 2019. Most publications have been enabled by international collaborations. Despite a significant lack of funding and infrastructure, most of the research is taking place within the public system. Increased funding within the public system, as well as public‐private collaborations, would allow for further research development.