bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Analysis of Factors Influencing Dementia Study Enrollment: Focus Groups with Diverse Community Members Viewing the ACTNOW Research Registry Website
Authors: Tran Leslie , Nunnerley Michael , Gothard Sarah , Golonka Ona , Pierce Aimee , Lindauer Allison 
Published: December 2022

AbstractBackgroundMany barriers discourage individuals from enrolling in dementia research studies, such as lack of information, web accessibility, and transportation. Research stakeholder feedback is necessary to understand these barriers. We used virtual focus groups to learn how to improve the website of our local research registry: ACTNOW (Alzheimer’s Comprehensive Treatment Network of Oregon and Washington). Local community members from diverse backgrounds interacted with the study team to provide insight on some of the roadblocks to research participation. Here, we report on findings from the focus groups and participants’ feedback related to the ACTNOW website and user engagement.MethodThree 90‐minute virtual focus groups (fg) were conducted with 19 participants via videoconferencing. Inclusion criteria were ACTNOW members, African American, and low‐income and rural‐dwelling individuals combined respectively. Participants completed pre‐and post‐focus group surveys about their thoughts on the ACTNOW website and interest in dementia research. Investigators from the research team analyzed the survey data and independently coded the written transcripts from the group discussions using the Dedoose coding software.ResultThere were 19 participants overall (fg_1=8, fg_2=5, fg_3=6). The mean age was 66.9; 89.5% of the sample was female; and 57.9% were white. The analysis revealed that the participants had concerns about the readability of the website and the clarity of purpose of ACTNOW (e.g., “I look at this, and I say, whoa, wait a minute they want me to sign up for what?”). Most of the topics discussed suggested consumers did not understand the purpose of the website or ACTNOW’s promotional materials, resulting in a fear of signing up for the actual program (research registry). Survey data reported a large interest in dementia research but a need for more consumable, relevant information, such as explaining the benefits of research and requirements of being an ACTNOW member.ConclusionFindings demonstrate specific website usability challenges and reasons that prevent community members from signing up for dementia research. Understanding the focus group participants’ feedback is important in fostering greater diversity, appeal, and accessibility in dementia research.
The systemic disruption of P2rx7 alleviates tau pathology in P301S tau mice via inhibition of extracellular vesicle release
Authors: Abdullah Mohammad , Ruan Zhi , Bueser Katrina Rae , Ikezu Seiko , Ikezu Tsuneya 
Published: December 2022

AbstractBackgroundP2X purinoceptor 7 (P2RX7), an ATP‐gated cation channel present abundantly in the microglia, induces membrane depolarization and extracellular vesicle (EV) secretion. Previous study demonstrated that administration of GSK1482160, a P2RX7 selective inhibitor, suppressed EVs secretion from murine microglia resulting in accumulation of Tsg101+ intraluminal vesicles (ILVs) in the hippocampus, and restored partial behavioral deficits in P301S tau mice. However, the specificity of GSK1482160 to P2RX7 has never been investigated in P301S tau mice. It is crucial to validate whether P2RX7 is a potential target for alleviating the tauopathy phenotype in P301S tau mice. The purpose of this study is to determine if deletion of P2RX7 is sufficient to recapiturate the therapeutic effect of GSK1482160 in tauopathy mouse model.MethodFours and nine‐months‐old P2RX7‐/‐:P301S and P301S mice were generated for the evaluation of ILV accumulation and tau pathology. Primary microglia and astrocytes from WT (C57BL/6) and P2RX7‐/‐ mice, treated with GSK1482160 and ATP for EV secretion. EVs were isolated from conditioned media via the sequential centrifugation and ultracentrifugation. Finally, EVs were quantified by nanoparticle tracking analysis and exosome specific marker CD9 ELISA. Effects of GSK1482160 on EVs secretion from astrocytes/microglia were also assessed using Western blot with EV specific markers Tsg101 and CD9.ResultExosome specific marker Tsg101, CD9, and tau expression levels were reduced in the hippocampus of nine‐months‐old P2RX7‐/‐:P301S mice compared to P301S mice. No significant difference between the two groups at 4 months of age was observed. Strikingly, primary cultured microglia and astrocytes showed reduction in EV secretion in both ATP stimulated or unstimulated condition from P2RX7‐/‐ group compared to WT group. Additionally, GSK1482160 pretreatment significantly reduced EV secretion from WT astrocytes and microglia, although it had no effects in P2RX7‐/‐ cells. These findings were validated by ELISA of EV marker CD9 and immunoblotting of Tsg101 and flotillin‐1 using isolated EVs.ConclusionResults demonstrate that P2RX7 is primarily responsible for ATP‐induced EV secretion from astrocytes and microglia, and systemic disruption of P2RX7 mimics the effect of GSK1482160 in P301S tau mice, including accumulation of ILVs in microglia and suppression of tau accumulation in the hippocampal regions.
RNA Analysis of Laser‐Captured Neurons, Microglia and Astrocyte After Intracerebroventricular Injection of Neural Stem Cell‐Derived Exosomes
Authors: Saieva Salvatore , Guptarak Jutatip , Zhang Wenru , Johnson Kathia M , Micci Maria‐Adelaide , Taglialatela Giulio 
Published: December 2022

AbstractBackgroundNeural stem cells (NSC) and adult neurogenesis are known to modulate synaptic plasticity and cognitive function. Decreased number of NSC have been reported in Alzheimer’s Disease (AD), whereas their increase is associated with improved learning and memory. However, an increased neurogenesis does not correlate with preserved cognition, thus suggesting that other mechanisms involving increased numbers of NSC promote the preservation of memory. NSC are also known for their capacity to secrete exosomes, microvesicles containing cell‐specific cargos of biomolecules, that are taken up by other cells, thus modulating their function. We and others have shown that NSC‐derived exosomes (NSCexo) injected in brains of AD transgenic mice models ameliorated the cognitive decline and decreased the binding of toxic oligomers to synapses. The mechanisms by which NSCexo provide protection to synapse is still under investigation. Our long‐term goal is to find the specific genes modulated by NSCexo that may be responsible for the cognitive resilience and the overall improvement of CNS function. With this goal in mind, here we determine the cell‐specific (neuron vs. glia) uptake of NSCexo and subsequent cell‐specific changes in gene expression.MethodC57Bl/6 mice received fluorescent‐labeled NSCexo via intracerebroventricular injection; after collection of brain samples, immunofluorescence on brain slices were performed to identify neurons, astrocytes and microglia. The colocalization of NSCexo with neuronal, astrocytic and microglial markers was evaluated. The single cell types were subsequently laser‐captured, and their RNA was isolated. Single‐cell RNA analysis was performed to investigate differences in RNA expression comparing not‐injected and injected animals.ResultWe found that NSCexo are taken up preferentially by neuronal cells, but also astrocyte and microglia, thus leading to the modulation of relevant gene expression. Interestingly, we also found a pronounced uptake of NSCexo in the sub‐granular area of the hippocampus dentate gyrus, likely by NSCs.ConclusionOur results suggest targeting of neurons (and to a lesser extent, astrocyte and microglia) by NSCexo. They also suggest important targeting of NSC themselves, in what appear to be an autocrine signaling mechanism deserving further in‐depth investigation. Collectively, these mechanisms may play a key role in the reported involvement of decreased NSC and neurogenesis in AD.
Study: A Retrospective Claims Analysis of Preventable Hospitalizations Among Wisconsin Medicaid Beneficiaries with Dementia ‐ 2016 Through 2019
Authors: Felten Kristen M. , Steinmetz Cory 
Published: December 2022

AbstractBackgroundOlder adults with Alzheimer’s Disease and Related Dementias (ADRD) are often more vulnerable to severe illness and injury than older adults without ADRD. A percentage of the causes of these hospitalizations are considered preventable with good care management. To quantify the impact of the resulting preventable hospitalizations, the Wisconsin Department of Health Services has performed an evaluation using claims data in a retrospective analysis.MethodUsing Wisconsin Medicaid claims records from the beginning of 2016 through the end of 2019, leading preventable causes of hospitalization among older Medicaid beneficiaries were identified, and rates of hospitalization for those with ADRD were compared against those without ADRD. Hospitalizations with certain diagnostic codes were considered “preventable” if timely outpatient care or simple precautions are known to resolve or avoid intensive hospital care. Direct costs to Medicaid for hospital stays were also tabulated, as well as differences by race/ethnicity and living arrangements.ResultsPreliminary aggregate results indicate higher rates of preventable hospitalization for older beneficiaries with ADRD than those without ADRD, especially for sepsis, urinary tract infections, and pneumonia. Rates of hospitalization were higher for racial and ethnic minority populations than for the white population, and an ADRD diagnosis was a larger risk factor for hospitalization in home and assisted living settings compared to a nursing home setting.ConclusionThe cost to the health of the person with dementia, the cost to the family, and health care costs associated with a few key preventable conditions is extraordinary and unnecessary. Use of this data can drive the development of policies and practices that address risk factors for these conditions that could improve the quality of life for the person living with dementia by preventing unnecessary illness and/or injury, but could also lower unnecessary costs for families and health care systems.
Neuroimaging Findings in a Racially and Ethnically Diverse Cohort of Oldest‐Old Individuals: The LifeAfter90 Study
Authors: Corrada Maria M. , Gilsanz Paola , Tran Diana , Al‐Darsani Zeinah , Mungas Dan M. , Glymour M. Maria , Kawas Claudia H. , DeCarli Charles S. , Whitmer Rachel A. 
Published: December 2022

AbstractBackgroundNeuroimaging biomarkers are important and widely used in dementia research. Such studies, however, are rare in the oldest‐old and essentially non‐existent in ethnically diverse oldest‐old populations where the prevalence of cognitive impairment is greatest and dementia due to multiple pathologies. Here we present initial neuroimaging findings in the LifeAfter90 Study, a racially and ethnically diverse cohort of oldest‐old individuals.MethodsLifeAfter90 is a cohort of long‐term members of a health‐care system aged 90+ without a dementia diagnosis in their medical record at recruitment and clinical assessments every 6 months. Of the >800 participants enrolled, a subset agreed to brain imaging (MRI and amyloid PET). Hippocampal volume (HV) and white matter hyperintensities (WMH) were normalized to intracranial volume and WMH was log transformed. Amyloid burden was quantified as the mean SUVR values of 4 regions and dichotomized with an SUVR cutpoint of 1.10. Mean neuroimaging marker levels were compared between ethnoracial groups with analysis of covariance adjusting for age.ResultsTo date, 99 individuals have undergone an MRI and 90 an amyloid PET scan. The average age at the time of scan was 93 years, 60% of participants were women, and 43% had college education or higher (Table 1). Unadjusted values of neuroimaging findings are in Table 1 and adjusted means in Table 2 and Figure. In our preliminary data, we see 44% amyloid positivity overall. Black individuals have the lowest proportion of amyloid positivity (32%) but among the highest WMH mean volume, whereas Latino individuals have the highest proportion of amyloid positivity (64%) and lowest WMH mean volume. Asian individuals had the highest mean hippocampal volume. Except for SUVR differences in Black vs Latino individuals (p=.04), there were no group differences in mean levels (Figure).ConclusionsWe present neuroimaging findings from a first‐of‐its kind multi‐ethnic cohort study of oldest‐old individuals. Although too early to test for differences due to the small number of individuals, we have indications of ethnoracial differences in levels of neuropathologies consistent with those of younger elderly. Determining the utility of neuroimaging biomarkers for identifying future disease in these individuals is essential for advancing cognitive research.
The COEQUAL Registry: Creating Opportunities to Increase Health Equity & Equality for Persons at Risk for AD/ADRD
Authors: Balls‐Berry Joyce E , Mozersky Jessica , Postman Whitney , Denny Andrea , Xiong Chengjie , Kannampallil Thomas , Thompson Vetta Sanders , Hassenstab Jason J. , Gabel Matthew , Hill Carl V. , Saunders John , O'Leary Catina , Griffin Stephanie , Johnson Charis , Moulder Krista L. , Morris John C. 
Published: December 2022

AbstractBackgroundCommunities with the highest disease burden from Alzheimer’s disease and related dementias (ADRD) often experience considerable health disparities. These disparities are due to systematic and structural racism, classism, ageism, and social determinants of health, leading to distrust of and lower engagement with biomedical research. These injustices exacerbate disparities, ultimately leading to less generalizability of research findings. Therefore, we hypothesized that creating a culturally appropriate ADRD research registry called COEQUAL would increase underrepresented communities' engagement in ADRD research.MethodsOur NIH‐funded community and patient‐engaged study aims to identify and enhance current practices to promote high‐yield engagement and retention of diverse participants in ADRD research in St. Louis, Missouri. Based at the Washington University Knight Alzheimer’s Disease Research Center, our partners include Saint Louis University, Wesley House (a social service organization), the Greater Missouri Chapter of the Alzheimer’s Association, and Health Literacy Media. We have a 20‐member Governance Board to create a culturally appropriate research registry. Before creating the COEQUAL registry, we plan to conduct a community needs assessment with listening sessions and a pre/posttest survey of n = 160 community members, patients, caregivers, and healthcare providers aged 45+. We will use direct/indirect recruitment methods like posts in the health system patient portal, social media, and emails/mailers to recruit participants. Our facilitator’s guide and a pre/posttest survey will contain validated and culturally appropriate items to gauge perceptions, practices, and knowledge related to ADRD, willingness to participate in an ADRD research registry, and ways to engage and retain diverse participants. We will oversample participants who self‐identify as Black (African American, African, African Caribbean, or African Ancestry). Findings from the community needs assessment will be used to inform recruitment, ongoing engagement with, and retention of, individuals in ADRD research.ResultWe anticipate gaining knowledge of the perceptions and practices of engaging community members, patients, and providers in creating a culturally appropriate ADRD research registry.ConclusionThe feasibility of creating a culturally appropriate ADRD research registry in St. Louis is critical to ensure justice and generalizability in research. Moreover, using a community and patient‐engaged research approach increases the cultural appropriateness of ADRD research.
Which NODDI implementation is nicest for diffusion MRI?
Authors: Reid Robert I. , Kamykowski Michael G. , Gebre Robel K , Jack Clifford R. , Vemuri Prashanthi 
Published: December 2022

AbstractBackgroundNeurite Orientation Dispersion and Density Imaging (NODDI) is becoming increasingly common as multiband acceleration becomes available for clinical scanning, but fitting the model can be extremely slow. Since the release of the original MATLAB implementation in 2012, three alternatives have become popular: Accelerated Microstructure Imaging via Convex Optimization (AMICO), the Microstructure Diffusion Toolbox (MDT), and the CUDA Diffusion Modelling Toolbox (cuDIMOT). They accelerate fitting through reformulation and/or using GPUs, but the implementation differences raise the question of which approach is best. To our knowledge all previous comparisons lacked knowledge of the true values and used the original implementation as the nominally correct one, with in vivo data. We remedy that using simulations with known NODDI values, in addition to in vivo scans.MethodWe created a software phantom with Neurite Density Index (NDI) values linearly increasing from 0.1 to 1.0 in x, Orientation Dispersion (ODI) from 0 to 1 in y, and Isotropic water Volume Fraction (ISOVF) from 0 to 0.9 in z. We simulated five scans using the ADNI3 advanced diffusion MRI protocol. The phantom had 20 voxels in each direction, and the fiber bundle principal direction randomly varied between the simulations. The simulations were fit by the original, AMICO, MDT, and cuDIMOT implementations, and root mean square errors were calculated as shown in Table 1. A discrepancy measure was also calculated using the brain voxels of three in vivo human scans acquired using the same protocol on a Siemens Prisma, substituting the original implementation’s values for the truth since the latter is unknown for in vivo scans.ResultcuDIMOT had the least error (for ODI < 0.8) and was fastest. The original implementation was a close second in accuracy but much slower. cuDIMOT’s ODI underestimation can be corrected with a transfer function in the noise‐free case, but that approach fails with actual scans.ConclusionThe original or cuDIMOT implementations should be used, with cuDIMOT the favorite when at least one CUDA‐capable GPU is available and the number of scans are large. Correcting cuDIMOT’s ODI underestimation using a different initialization or form of Dawson’s integral should be investigated.
MRI norm percentile in age‐related atrophy starts from MCI stage
Authors: Arakaki Xianghong , Butler Ryan , Kang Jimmy , Macias Thomas , Chui Helena C , Nolty Anne , Spezzaferri Mitchell , Sin Caleb , Rising Shant , Molloy Cathleen , Kloner Robert A , Fonteh Alfred N. 
Published: December 2022

AbstractBackgroundAge related atrophy occurs in Alzheimer’s disease and related dementia (ADRD). Although atrophy was reported in early stage as mild cognitive impairment (MCI), the knowledge about earlier changes is limited. To fill this knowledge, we explored the age‐related atrophy in our pilot MRI database when participants at different stages of ADRD.MethodMRI data are analyzed using NeuroQuant. We studied MRI data in cognitively healthy (CH, n=74) individuals when their cerebrospinal fluid (CSF) amyloid/tau ratios were normal (CH‐NATs, n=18) or pathological (CH‐PATs, n=41), in participants with impaired or MCI (n=9), and Alzheimer’s disease (AD, n=6), and other dementia (OD, n=6). We explored age, gender‐corrected norm percentiles for atrophy analysis in age‐related structures – (including hippocampal occupancy score (HOC, percent of hippocampi volume relative to inferior lateral ventricle volume), hippocampi, entorhinal cortex, and inferior lateral ventricles) and whole brain, cerebral white matter. We compared the data between CH, MCI, AD, and OD, compared between CH‐NATs and CH‐PATs, and compared between CH with cerebrospinal fluid (CSF) amyloid pathology (ChA+, n=15) and CH without CSF pathology (ChA‐T‐N‐, n=13) based on CSF Aβ42, phosphor‐tau (p‐tau), and total tau (t‐tau). Bonferroni correction was used for Multiple comparisons.ResultAnalysis of MRIs collected at HMRI show neuro‐quantitative data in CH participants compared to MCI, AD, or OD, and MCI to AD and OD. Compared to CH, MCI have decreased HOC and larger superior lateral ventricle (Table 1, Figure 1), AD have decreased HOC, hippocampi, whole brain, and cerebral white matter, and larger lateral ventricles, OD have similar changes except hippocampi (no change). No significant changes observed between MCI and AD or OD. No significant changes were observed between CH‐NATs and CH‐PATs, or between ChA+ and ChA‐T‐N‐.ConclusionDespite sample size limitation, these results suggest: 1) norm percentile is sensitive to age‐related atrophy at impaired stages, consistent with known changes; Whole brain volume decreases in AD and OD, only AD observed decreased hippocampal atrophy; 2) No apparent age‐related changes were observed in CH stage. Overall, MRI age‐ and gender‐corrected norm percentile for age‐related atrophy analysis is informative in individuals as early as MCI stage.
Sex differences in the protective effects of cognitive reserve
Authors: Chooi Cheyenne K , Gavett Brandon E , Weinborn Michael , Rainey‐Smith Stephanie 
Published: December 2022

AbstractBackgroundCognitive reserve is the term used to describe the apparent ability of one’s cognitive processes or neural networks to adapt in response to neuropathology and brain injury. This protective ability is proposed to account for individual differences in age‐associated cognitive decline and Alzheimer’s disease (AD) risk, where higher levels of cognitive reserve are associated with more preserved cognitive functioning and delayed onset of AD dementia. Women have a higher prevalence of AD than men, and account for two‐thirds of AD diagnoses. Sex differences in the protective ability of cognitive reserve may account for differences in Alzheimer’s disease prevalence between men and women, but few studies have explored this possibility. This study evaluates sex as a moderator of the relationship between cognitive reserve and brain volume effects on executive function.MethodThe study used archival data from 997 older adult participants in the Australian Imaging, Biomarkers, and Lifestyle(AIBL) Flagship Study of Ageing (see Table 1 for descriptives). Structural equation modelling was used to estimate a proxy for cognitive reserve and to run the analytical model. Cognitive reserve was defined as the variance in episodic memory not explained by demographics (e.g., education) and brain integrity (i.e., the residual reserve index; Reed et al., 2010). Executive functioning intercept and slope – derived from up to 7 study visits (18‐month follow‐up intervals) – were regressed onto the main and interaction effects of the residual reserve index, brain integrity (i.e., the combination of grey matter, hippocampal, and white matter hyperintensity volumes), and sex, plus covariates (e.g., number of apolipoprotein alleles; age).ResultA significant three‐way interaction was observed between cognitive reserve, brain integrity, and sex; Women benefitted more than men from the protective effects of cognitive reserve at comparably low levels of brain integrity. Further analyses also showed that women, on average, have higher levels of cognitive reserve as reflected by the residual reserve index.ConclusionSex differences in cognitive reserve highlight a potential sex‐related mechanism by which cognitive reserve confers protection against cognitive decline in the face of low brain integrity. These findings further our understanding of potential factors that maximise the protective effect of cognitive reserve.