bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal free‐water changes in dementia with Lewy bodies
Authors: Chiu Shannon Y , Chen Robin , Wang Wei‐en , Armstrong Melissa J , Boeve Brad F. , Kantarci Kejal , Vaillancourt David 
Published: December 2023

AbstractBackgroundDiffusion‐weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior dementia with Lewy bodies (DLB) studies focused on white matter or voxel‐based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. We aimed to characterize longitudinal diffusion microstructural changes in individuals with DLB.MethoddMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12‐ or 24‐months. Free water (FW) and FW‐corrected fractional anisotropy (FAT) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest from the Mayo Clinic Adult Lifespan Template. Primary outcomes were differences in FW and FAT between baseline and 12‐ or 24‐months.ResultWe identified 23 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI‐LB) from baseline to 12‐months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24‐months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time‐points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (p<0.05). We found significant differences in FW, but not FAT, from baseline to 12‐months. Significant increases in FW at both time‐points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (pfdr<0.05). We found additional more widespread microstructural changes from baseline to 24‐months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (pfdr<0.05). We found decreased FAT from baseline to 24‐months in the cerebellar and superior occipital regions (pfdr<0.01).ConclusionLonger follow‐up at 24‐months identified broader networks of free water changes in individuals with DLB. Results support dMRI as a promising, non‐invasive tool to track disease progression in DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB.
New polygenic risk score for Alzheimer’s disease impacts states and functions in iPSC‐derived microglia.
Authors: Therrien Martine , Atkeson Trevor , Meyer Daniel , Ghosh Sulagna , Turley Patrick , Stevens Beth 
Published: December 2023

AbstractBackgroundRecent genetics studies for Alzheimer’s disease have identified multiple risk variants affecting amyloid processing, immune response, lipid transport, and endocytosis, among others 1. More than half the risk genes associated with late‐onset AD are selectively expressed in microglia and peripheral myeloid cells. Yet, we know little about the underlying biology or how myeloid cells contribute to AD pathogenesis.MethodTo gain insights into the broad impact of genetics on microglia, we selected 50 cell lines from the CIRM biobank with variable APOE genotypes and polygenic risk scores (PRS). Building on our in vitro platform that recapitulates microglia states in vitro 2, we used villages 3, or pooled culture, to differentiate these lines into microglia and assessed key microglia functions, transcriptional profiles, and response to various perturbations.ResultCell villages allow us to compare phenotypes across lines with little technical variability robustly. Our data determined functional phenotypes that were altered by PRS and others that were affected by APOE genotypes. Moreover, quantitative trait locus (QTL) analysis identified new variants affecting phagocytosis, proliferation, and response to lipids. Finally, single‐cell RNA sequencing of our village pinpointed key microglia pathways altered between high and low PRS individuals.ConclusionCell village allows for the characterization of up to hundreds of cell lines while minimizing technical variability allowing us to identify phenotypes dysregulated across various genetic backgrounds. Our data pinpointed the impact of a novel Alzheimer’s disease PRS on microglia states and functions and identified new variants affecting microglia functions.1. Sims, R., Hill, M. & Williams, J. Nat Neurosci
23, 311‐322 (2020). 2. Dolan, M.‐J. et al. Biorxiv 2022.05.02.490100 (2022) https://doi.org/10.1101/2022.05.02.490100. 3. Wells, M. F. et al. Biorxiv 2021.11.08.467815 (2021) https://doi.org/10.1101/2021.11.08.467815.
Exploring cultural differences in the understanding of Alzheimer’s Disease and related dementias among Alaska Natives and providers in Alaska
Authors: Kim Steffi M , Lewis Jordan P. 
Published: December 2023

AbstractBackgroundThe proportion of the Native population aged 65+ is projected to increase between 2015 and 2045, from 7‐12%, and informal caregivers and health care providers are ill‐prepared to meet the demand of Alzheimer’s Disease and related disorders (ADRD). There is an increasing urgency to better understand Alaska Native views of ADRD.MethodGuided by Kleinman’s explanatory model of illness, a qualitative, research design was utilized to gather data on experiences with ADRD. 21 interviews with Alaska Native caregivers and 12 interviews with health care providers in rural and urban communities were completed. Using Nvivo qualitative software, thematic analysis was used to obtain cultural perspectives on ADRD. This study was approved by the University and tribal review boards.ResultMany Alaska Natives view ADRD as a natural part of the aging process, resulting in not always seeking medical care. Caregivers challenges included family denial, exhaustion and isolation, and family distancing themselves due to fear and limited understanding of ADRD. Caregiving benefits included spending time with older adult, learning family history, and sharing experiences with other caregivers. Healthcare provider challenges included rigidity of the healthcare system, no research on Alaska Natives, limited health literacy, limited community resources, and no knowledge of Alaska Native views of ADRD.ConclusionUnderstanding the cultural underpinnings of ADRD provides insight into how health care providers can integrate cultural beliefs into treatment to improve the processes of care that may mitigate the impact of ADRD on individuals and families. Culturally‐responsive education and training about ADRD is crucial to connecting Alaska Natives with ADRD to care that can assist them in aging more comfortably
LDs in AD: Lipid Droplet Dynamics are Modulated by APOE
Authors: Johnson Lance A 
Published: December 2023

AbstractBackgroundAging microglia accumulate lipid droplets (LDs), secrete pro‐inflammatory cytokines, and are defective in phagocytosis. The E4 allele of Apolipoprotein E (APOE) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD), and is associated with increased neuroinflammation and LD accumulation. We hypothesize E4 microglia have increased LD formation under basal conditions and a higher capacity to form LDs under stress, resulting in greater pro‐inflammatory cytokine production. Further, we hypothesize that APOE genotype modulates the LD proteome and lipidome at baseline and with inflammation.MethodsPrimary microglia from ApoE3 and ApoE4 mice were exposed to 250uM oleic acid (OA), 10ug/mL LPS, OA+LPS, dead N2A cells, or dead N2As+LPS, stained with BODIPY, and analyzed for LDs. For quantitative proteomics and lipidomics, we used liver tissue, which provides enough material for analysis. ApoE3 and ApoE4 mice were injected with saline (control) or LPS (5mg/kg) and perfused at 24h. LD‐enriched buoyant fractions were collected after density gradient centrifugation and analyzed for ‘omics.ResultsPrimary microglia from ApoE4 mice accumulated significantly more LDs at baseline, with OA, LPS, and N2As compared to E3 with reliable reproducibility. Western blots on LD fractions confirm LD enrichment via surface protein PLIN2. Proteomics revealed that LD fractions from E4 mice are enriched for proteins involved in innate immunity, while E3 LDs are enriched for proteins involved in lipid b‐oxidation. Lipidomics showed an increase in phosphatidylcholine ratio in the LD membrane of E4‐control and LPS‐treated droplets. Finally, many of the LD‐associated proteins identified by our screen are enriched in existing AD proteomics datasets, suggesting a potential role for LDs in AD pathogenesis.ConclusionE4 microglia accumulate more LDs compared to E3 microglia under all conditions tested. The proteomic profile of E4 LDs support the hypothesis that E4 expression increases inflammation under basal conditions, and upon stimulation, causes a more robust response. A better understanding of LD dynamics within glial cells and their functional implications during aging and AD may provide targets to improve E4‐related outcomes.
Analysis of Latino family caregiver engagement with CuidaTEXT, a text message intervention for dementia caregiver support
Authors: Perales Jaime 
Published: December 2023

AbstractBackgroundThe potential of text message caregiver support interventions to improve dementia care outcomes is still to be exploited. This study aims to explore participants’ engagement with a text message intervention for dementia caregiver support, and its association with acceptability and clinical outcomes. We hypothesize that a higher engagement with CuidaTEXT will be associated with increases in caregivers’ satisfaction with the intervention and decreases in depression.MethodCuidaTEXT is a six‐month, bilingual, and bidirectional intervention tailored to caregiver needs (e.g., education, problem‐solving, resources). We enrolled 24 Latino caregivers in a one‐arm feasibility trial. Participants received approximately one automatic daily text message. Participants could receive automatic on‐demand messages by sending specific keywords (e.g., STRESS for messages about stress coping) and on‐demand responses during business hours by chat‐texting with a live coach. In this secondary analysis, we calculated associations between the total number of text messages (engagement) and outcomes (primarily caregiver satisfaction and depression).ResultParticipants sent 1,847 messages to CuidaTEXT; 6.5% sent no messages (no engagement), 0.0% less than 10 (low), 29.0% between 10 and 49 (medium), 22.6% between 50 and 99, and 19.4% more than 100 (high). Engagement was associated with intervention satisfaction (r = 0.6, p = 0.007) and secondary acceptability outcomes (perceptions that CuidaTEXT provided help for their loved one with dementia: r = 0.6, p = 0.003; and to understand dementia: r = 0.6, p = 0.008) except for perceptions that CuidaTEXT provided help for themselves as caregiver (r = 0.3, p = 0.173). Engagement was not associated with change in caregiver depression (r = ‐0.0, p = 0.922) or secondary clinical outcomes (caregiving competence: r = 0.4, p = 0.104; and behavioral symptom‐related distress: r = 0.4, p = 0.076).ConclusionText message engagement is associated with satisfaction but not depression. Encouraging interaction with CuidaTEXT might lead to higher levels of satisfaction with the intervention. However, future research should determine the directionality of these associations.
Analyzing Phytoextracts based nano‐emulsion system for the neuroprotective activity against Alzheimer’s disease
Authors: Jindal Divya , Singh Manisha 
Published: December 2023

AbstractBackgroundAccording to the WHO projections globally, dementia has afflicted roughly 55 million people worldwide by 2022, with 10 million new cases being identified every year. Thus, from this data information, we can conclude that central nervous system (CNS) disorders are becoming more common and prevalent worldwide. And amongst all CNS‐related diseases, one of the most concerning aspects is the prevalence of Alzheimer’s disease which has become the most common trait in the world’s ageing population. AD is also known as the most challenging kind of dementia to cure. Pathologically in AD, the static loss of cortical neurons causes the deterioration of neuronal connections and circuits, which results in a range of progressive neocortical degeneration linked to the buildup of Aβ plaques. It is challenging to treat AD due to a number of inescapable physiological limits, including circulation blockages, medication permeability and degradation, and other factors. As a result, the drug’s capacity to reach the brain’s afflicted regions is restricted, and the CNS is unable to absorb therapeutic molecules passively.MethodTherefore, the idea of nanotherapeutics has evolved into a feasible technique for CNS‐based drug delivery. In our research, we computationally assessed the efficacy of the traditionally renowned Indian Ayurvedic medicinal plants Bacopa monnieri and Withania somnifera, used for their capacity to provide neuroprotective effects, especially in the case of CNS disorders. After being altered to achieve the nanometric size range, they were then created for the nano‐emulsions system.ResultAccording to the computational findings, synthetic extracts had a higher binding affinity for CNS‐related biomarkers than conventional medicines. Subsequently, using an aqueous titration approach, an oil‐in‐water (o/w) nano‐emulsion system was devised for Withania somnifera and Bacopa monnieri standard extracts in suitable and optimized excipients (Almond oil, Triacetin, Ethanol). The nanometric size range (100‐300 nm) of the optimized nanoformulations showed a substantially higher level of neuroprotective potential than their extracts, according to the characterization results.ConclusionIn conclusion, the present study demonstrates that the developed formulation has potential therapeutic effects on improving the pathological state of AD, and might be taken further as a promising candidate for clinical research to evaluate its efficacy in human.
Preliminary results of a feasibility study of CONFIDENCE: An intervention to reduce financial strain among Latino family caregivers
Authors: Meyer Kylie , Gonzalez Alexander , Mage Susanna , Silva David , Rodriguez Rocio Aguila , Benton Donna Marie 
Published: December 2023

AbstractBackgroundLatino/Hispanic family caregivers to persons living with Alzheimer’s disease and related dementias (ADRD) spend 47% of their annual income on the out‐of‐pocket costs of caregiving compared to 26% of annual income spent among caregivers of any race or ethnicity.1 This presentation describes the preliminary results of the CONFIDENCE psychoeducational intervention, developed to reduce the out‐of‐pocket care costs and financial strain among ADRD Latino/Hispanic caregivers. Intervention components were designed to build caregiver resourcefulness, posited to help caregivers displace some out‐of‐pocket costs by increasing the use of community resources. CONFIDENCE consists of five, 1.5‐hour group Zoom sessions. To ensure the intervention was culturally tailored, CONFIDENCE was developed with a Community Advisory Council and informed by qualitative interviews with Latino family caregivers.MethodCONFIDENCE has been delivered at a community agency since May 2022. Data reported here are from the first 5 intervention cohorts. Participation in the study was optional. Study participants were asked to complete a self‐administered online baseline survey before the first session, followed by two surveys sent immediately and 2‐months post‐intervention. Eligible caregivers were Latino/Hispanic, cared for someone living with ADRD for at least 6 months, and were aged 50 or older. (See NCT05292248.) All sessions were delivered in English. Spanish delivery will begin in March 2023.ResultCONFIDENCE was delivered to 27 caregivers, although 55 caregivers registered to attend (49.1%). Of those who attended any of the five sessions, participants attended an average of 2.9 of 5 (SD = 1.4) sessions. Among those who attended at least one session, 56.5% expressed an interest in learning more about the research study when they registered. Of those, six caregivers were eligible to participate and enrolled into the study. Despite lower‐than‐expected participation, those who completed the intervention report high satisfaction. All study completers “Agreed” or “Strong Agreed” that they would recommend CONFIDENCE to others.ConclusionInitial findings suggest a 5‐week, Zoom‐delivered financial psychoeducational intervention may only meet the needs of a narrow portion of ADRD Latino family caregivers. To increase participation, researchers intend to explore alternative forms of delivery that require less time commitment.References:1.Skufca L, Rainville C. Caregiving Out‐of‐Pocket Costs. 2021. AARP Research. https://www.aarp.org/content/dam/aarp/research/surveys_statistics/ltc/2021/family‐caregivers‐cost‐survey‐2021.doi.10.26419‐2Fres.00473.001.pdf
Cultural adaptation of a mobile caregiver intervention application for Hispanic caregivers of persons with dementia (PWD)
Authors: Rodriguez Miriam J. 
Published: December 2023

AbstractBackgroundFamily caregivers for persons with dementia (PWD) in the U.S. who identify as part of a racial or ethnic minority group experience higher levels of depression, receive less support from home and community‐based services, and often cannot access services in their primary language. The Alzheimer’s Association has recommended that proven interventions be adapted to address the needs of informal caregivers from different racial and ethnic backgrounds. Although several clinical interventions have been developed with promising results to improve the overall caregiving experience of PWD, the effectiveness of current interventions for Hispanic caregivers of PWD are unclear. Mobile, technology‐based interventions may address specific needs of Hispanic caregivers of PWD such as providing at home access to culturally tailored interventions, but current mobile caregiver interventions do not sufficiently consider equity factors. In the current study, we will culturally adapt an existing, validated, mobile caregiving intervention app for Hispanic caregivers of PWD using an equity focused framework.MethodBrain CareNotes was guided by the NIH Stage Model for Behavioral Intervention Development and is a secure mobile telehealth application for informal caregivers to manage behavioral and psychological symptoms of dementia (BPSD) with the aid of a remote care coach. To culturally adapt this intervention, we will addresses stage 0 – 1 of the NIH Stage Model and apply a previously developed equity framework, PROGRESS‐Plus, which identifies specific cultural factors (i.e. Place of Residence, Race/ethnicity, etc) that should be considered in the development of equity focused interventions. We will qualitatively identify specific PROGRESS‐Plus needs that are insufficiently met among Hispanic caregivers of PWD through semi‐structured interviews. We will incorporate this information in the modification of Brain CareNotes, which will be made using a participatory co‐design methodology. Two groups of n = 5 Hispanic English and Spanish speaking caregivers of PWD will participate in five co‐design sessions to adapt the intervention to meet identified PROGRESS‐plus related needs. The adapted intervention will then be pilot tested.ResultDescription of this ongoing study will be presented.ConclusionThis will result in an extensible framework for modifying and culturally tailoring other previously developed caregiver interventions for ethnic minority groups.
The health economics of an Alzheimer’s prevention therapy
Authors: Mattke Soeren , Jun Hankyung , Hanson Mark , Chu Samantha , Kordower Jeffrey H. , Reiman Eric M. 
Published: December 2023

AbstractBackgroundAmyloid reducing antibodies have been shown or suggested to slow decline in early Alzheimer’s disease (AD), and prevention trials in preclinical AD are ongoing. We estimate cost‐effectiveness of AD prevention from a payer perspective, which considers cost offsets and QALYs gains, and a societal perspective, which adds reduction in caregiver burden.MethodWe estimate cost‐effectiveness in the 2023 cohort of 55–79‐year‐olds with a Markov model under the following assumptions: Everyone would undergo an AD blood test (cost $125), which would generate positive or negative results in 80% of cases with sensitivity and specificity of 80% and inconclusive results in 20%. Individuals (80%) testing positive would go directly to treatment, the other 20% to confirmatory testing with PET (50%, cost of $4,000) or CSF (50%, cost of $600), receiving treatment accordingly. Individuals testing negative at any stage would return for another blood test in five years and those with inconclusive results in one. We assume average annual therapy cost of $5,850 per person (the list price of the PCSK9 inhibitors) for duration of 12 years, treatment effect of 50%, and four (baseline and 6, 12 and 18 month) MRIs ($400) for ARIA.ResultThe program would be cost‐effective from a payer perspective with cost of $45,157 and value of $53,721 per person. From a societal perspective, it would generate $24,704 in net value per person (Figure 1). If the treatment delayed progression by 25 percent, the program would no longer be cost‐effective from a payer or societal perspective. The treatment would have to eliminate the progression from preclinical AD to MCI to become cost‐neutral (Figure 2). Higher specificity of the blood test would decrease cost per person with no change in value generation and higher sensitivity would increase cost and decrease valueConclusionA prevention treatment that reduces the progression from preclinical AD to MCI by 50% could be economically viable from a payer perspective. The results are preliminary and need to be adjusted as more data become available, but the findings should stimulate a discussion among stakeholders about the contours and economic viability of such a prevention program.