bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for effect modification by serum clusterin on dendritic cells in association with dementia
Authors: Vivek Sithara 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) and AD related dementias (ADRD) are complex heterogeneous diseases with multiple pathogenic mechanisms. Previous experimental studies showed that serum clusterin has a significant role in the maturation of dendritic cells (DCs). Studies showed that myeloid DCs (mDCs) in blood were dysregulated in AD and higher levels of serum clusterin related to higher incidence of dementia. We evaluated the association of DCs in peripheral blood and serum clusterin and their interaction with AD/ADRD.MethodWe used data from 3072 participants in the Health and Retirement Study (HRS) who participated in the 2016 Venous Blood Study (VBS), and had flow cytometry, clusterin and cognition assessed. We used generalized survey logit models to evaluate the association between the DCs, clusterin, and dementia after adjusting for age, sex, race, education, comorbidity, body mass index (BMI) and Cytomegalovirus (CMV) seroprevalence. Utilizing the RNAseq data, we performed differential gene expression (DGE) analysis on DCs, clusterin and dementia to identify overlapping genes in the biological process.ResultWe found that after covariate adjustment, a higher percentage of dendritic cells was associated with lower odds of having dementia (OR = 0.61, 95% CI: [0.44, 0.86]; p = 0.005). We found that higher levels of serum clusterin was associated with higher odds of having dementia. This relationship was somewhat attenuated after covariate adjustment (OR = 1.07, 95% CI [0.99, 1.16], p = 0.09). We found a significant interaction between serum clusterin and DCs in the association with dementia (p = 0.02) with those having low DCs and high clusterin being at increased ADRD risk (OR = 1.25) and those with high DCs and low clusterin being at lower ADRD risk (OR = 0.48) as compared to those who have both low DCs and low clusterin. We identified three genes (TUBB4A, WASHC5 and GSTA4) that were dysregulated in the pathways of DCs and clusterin in association with dementia.ConclusionThis study has shown, for the first time, an interaction between serum clusterin and DCs in peripheral blood that is associated with increased risk of dementia in a large sample of older adults that needs to be validated in future studies.
Virtual Respite for Family Caregivers
Authors: Washington Tiffany R , Rapowitz Jennifer 
Published: December 2023

AbstractBackgroundThere are over 11 million family caregivers to individuals living with Alzheimer’s in the U.S. The risk of caregiver burden and the inaccessibility of institutional respite create a need for in‐home respite programs. This proof of concept study examined the feasibility of an in‐home virtual respite program.MethodFamily caregivers of individuals with mild dementia received up to six student delivered in‐home virtual respite visits over two months. Semi‐structured interviews were conducted with family caregivers and student participants following the visits. The qualitative data were analyzed using thematic analysis with three coders.ResultFamily caregivers reported that the virtual respite program allowed time to engage in self‐care activities such as rest, exercise, and social interaction.ConclusionThis novel intervention freed time for family caregivers to receive respite in a virtual format. A future randomized trial is needed to estimate the effect of the intervention on psychosocial and clinical outcomes.
Contribution of a dysfunctional variant of ALDH4A1 to Alzheimer’s Disease pathology through altered metabolism and mitochondrial impairment
Authors: Kraemer Benjamin R , Mochly‐Rosen Daria 
Published: December 2023

AbstractBackgroundAldehyde dehydrogenases (ALDH) are enzymes which oxidize toxic aldehydic species into carboxylates. ALDH4A1 is a mitochondrial, NAD+‐dependent, dimeric enzyme and oxidizes the toxic aldehyde glutamic‐g‐semialdehyde (GSA) to glutamate. ALDH4A1 lies at the nexus of proline and arginine metabolism, the TCA cycle, and mitochondrial health (Fig. 1). The substrate of ALDH4A1, GSA, inactivates vitamin B6 (Farrant et al., 2001), an essential cofactor for amino acid and neurotransmitter biosynthesis. Toxic aldehydes like 4‐hydroxynonenal (4‐HNE), are elevated in Alzheimer’s Disease (AD) patients (Markesbery & Lovell, 1998) and promote amyloid‐b aggregation (Siegel et al., 2007). A recent genetic analysis identified a missense variant of ALDH4A1 as a risk factor for Late Onset Alzheimer’s Disease (LOAD) (Wang et al., 2015). Our previous analysis found that ALDH4A1 is an essential enzyme with no common loss of function variants (Chen et al., 2021). Our work elucidates the contribution of ALDH4A1 to AD pathology.MethodRecombinant protein was characterized to determine changes in protein activity and stability. The AD risk factor mutation was knocked‐in to the endogenous locus of induced pluripotent cells to monitor mitochondrial health, metabolism, and AD biomarkers. Mouse embryonic fibroblasts that do not express ALDH4A1 were used to monitor protein stability in cellulo.ResultThe AD associated variant of ALDH4A1 has decreased activity compared to wildtype (WT) (Fig. 2). ALDH4A1 can oxidize the toxic AD‐associated aldehyde 4‐HNE, and the variant has 50% of the activity of WT with 4‐HNE (Fig. 2). The variant enzyme is less stable in cellulo; variant ALDH4A1 is degraded within a few hours compared to WT that remains stable up to 24 hours. Knock‐in cells accumulate 25% more extracellular proline, and show a trend towards increased intracellular proline, indicating faulty proline metabolism in cells expressing the AD‐associated mutant ALDH4A1.ConclusionALDH4A1 oxidizes AD associated aldehydes (i.e., 4‐HNE) in addition to its known substrate. The AD‐associated variant of ALDH4A1 is less catalytically active and less stable than the WT enzyme. Cells expressing this variant have dysregulated proline metabolism. These data indicate that ALDH4A1 variants may contribute to AD through altered metabolism and increased aldehydic load from dysregulated protein activity and stability.
Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants
Authors: Ma Lingzhi 
Published: December 2023

AbstractBackgroundFew epidemiological studies in the adult population related these outcomes to daytime sunlight exposure.MethodData were from a prospective cohort of 362094 UK Biobank participants. Questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. Restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia.ResultMore specifically, we prefer to describe this nonlinear relationship with J shape, the lowest risk at three change points (1.5 hours/day on average, 2 hours/day in summer, and 1 hour/day in winter). Since for sunlight exposure, a marked increase in risk was observed at low exposure, but a relatively slow elevation in risk at higher exposure.ConclusionThere is a J‐shaped correlation between outdoor sunlight exposure time and dementia risk.
Population‐based Dementia Identification and Care Coordination: The CS CARES Program
Authors: Tan Zaldy S , Qureshi Nabeel , Kremen Sarah , Rhinehart Deana , Gatmaitan Dyane , Spivack Erica , Guinto Augustine , Sicotte Nancy 
Published: December 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) afflict over five million persons in the U.S., and persons living with dementia (PLWD) have been shown to receive poor quality care and experience worse health outcomes compared to those without ADRD. While dementia care programs have been shown to improve these outcomes, to date, the effects have not been studied in a value‐based Medicare population.MethodsIn a large multi‐specialty medical group practice, we identified patients enrolled in a value‐based insurance program (Medicare Advantage) using the EPIC electronic health record (EHR). Patients were eligible to enroll in a care coordination program if they had an ICD‐10 diagnosis of ADRD in the EHR problem list and/or past medical history, or currently taking an FDA‐approved medication for ADRD. We invited eligible patients to enroll in the CARES dementia care program and additionally included patients with ADRD who have a primary care provider in the health system. A study‐assigned nurse practitioner (NP) identified the patient’s medical, behavioral, and psychosocial needs using the novel CEDARS‐6 dementia care tool to formulate and share a care plan with the patient’s primary care provider. Regular check‐in calls were scheduled, and care plans were updated based on patient’s status. To evaluate patient and caregiver baseline health status, we assessed patient behavior (NPI‐Q), caregiver stress [Modified Caregiver Strain Index (MCSI)], and caregiver depression (PHQ‐9).ResultsWe enrolled 195 (33.1%) of eligible patients, with non‐responders to the invitation accounting for the majority (75%) of non‐enrollees. The average age of enrollees was 81.3 (SD = 9.16) years old, 64.6% were female, and 81.2% identified English as their primary language. Based on caregiver report, patients scored an average NPI‐Q Severity score of 10.40 (6.87), and an average NPI‐Q Distress score of 13.80 (10.54). Caregivers scored an average PHQ‐9 score of 5.65 (5.28) and MCSI score of 10.62 (7.01).ConclusionPLWD proactively enrolled in a dementia care program have high baseline rates of behavioral issues and their caregivers have elevated depression and stress scores. It is important to track the longitudinal effects of the CARES dementia program on these measures.
Call and response: Ethnomusicological methods to awaken specific memories with targeted songs encoded in neuronal populations of a dementia patient
Authors: Pillay Jayendran 
Published: December 2023

AbstractThis study collaborates with a fellow expert ethnomusicologist Sean Williams to trigger specific contextual memories associated with songs of her mother Julian Williams, born in 1932, and currently struggling with the early stages of dementia. The goal was to ascertain the success rate of a one‐to‐one correspondence type: The use of targeted, known songs of the dementia patient as a means to trigger the patient’s contextual memories.By adopting a methodology in Ethnomusicology involving the autobiography of one’s music history and their corresponding memories of the patient Julian Williams, I set up the experiment for Sean Williams to conduct. Dividing the study into discrete music time periods (infancy, childhood, teenager, young adult, older adult), I asked Sean Williams to choose specific songs with specific memories to the patient to be sung. The memory responses of the patient on video were then recorded.Each of those songs had deep levels of recognition by the Alzheimer’s patient, as evidenced in her singing with some memories (lyrics and contextual environment) stronger than than others. The fact that there is some autobiographical recall, despite a weakened sense of time and space after the onset of Alzheimer’s, suggests there may be use for this technique in dementia care. Of note, is the fun‐filled disposition of the participants during the recording of the singing. That speaks to a higher quality of life one could expect by using music as a memory‐recall and time‐ travel companion.This single case study needs to be broadened into a larger‐scale experiment involving many participants from different cultures to ascertain the use of individualized targeted songs to awaken specific memories of the dementia patients. In the area of dementia care, this approach also makes it possible for families to participate actively since the songs will probably be known to them as well.
TeleCARE: A telehealth group to teach dementia caregivers how to manage neuropsychiatric symptoms
Authors: Shirk Steven , Moo Lauren R. , McLaren Jaye E. , Pugh Kendra , Nguyen Andrew H. , O'Connor Maureen K. 
Published: December 2023

AbstractBackgroundNegative outcomes associated with caring for a loved one with ADRD include increases in caregiver depression, anxiety, and burden often due to managing neuropsychiatric symptoms (NPS). CARE is an in‐person, group‐based behavioral intervention that teaches caregivers specific skills to manage the NPS that are common in ADRD. Prior to the COVID‐19 pandemic, we were funded to adapt the CARE program to a virtual format (TeleCARE) in order to improve access to specialized services for caregivers with barriers to in‐person care. The impact of COVID‐19 further underscored the importance of telehealth interventions for caregivers.MethodTwenty caregivers participated in TeleCARE using the Cisco Webex platform. Caregivers were predominately female (80%), spouses (80%), ranging in age from 35‐88 (M = 70.8). The CDR‐Sum of Boxes was administered to measure dementia severity of the care recipients with a mean of 11.1 (moderate dementia). Data were collected at baseline and immediately following completion of the 8‐week group intervention.ResultEighty‐five percent of caregivers had a better understanding of NPS, and 90% of caregivers felt TeleCARE helped them take better care of the person with dementia and improved their ability to manage caregiving. Caregivers reported reduced depression and anxiety following the intervention (BDI: M = 9.6 vs M = 7.8; BAI: M = 8.7 vs. M = 6.8). They also reported increases in Positive Aspects of Caregiving (M = 33.2 vs. M = 35.3) and Meaning and Purpose in Life (M = 53.7 vs. M = 55.3). They reported little reduction in distress related specifically to NPS (M = 20.3 vs. M = 19.7).ConclusionThe TeleCARE adaptation was successful, with caregivers reporting improvements in understanding of NPS, caregiver depression and anxiety, ability to care for their loved one, and management of caregiving tasks. Even with the return to in‐person care options after the peak of the COVID‐19 pandemic, the nature of dementia caregiving often does not allow caregivers to easily leave home to join in‐person programs. Geographical distance, time, and money spent finding care for loved ones can be barriers to participation. Our results suggest TeleCARE may serve as an effective option to increase access to group caregiver education and support.
Biological sex and vessel specific relationships between cerebral pulsatility and white matter hyperintensities: a 4D flow MRI study
Authors: Moir M. Erin , Fico Brandon G. , Loggie Nicole A. , Gaynor‐Metzinger Sarean H.A. , Norby Alexander M. , Howery Anna J. , Rivera‐Rivera Leonardo A. , Eisenmenger Laura B. , Wieben Oliver , Johnson Sterling C , Barnes Jill N. 
Published: December 2023

AbstractBackgroundBrain vascular dysfunction is a contributing factor to the increased risk of Alzheimer’s disease with advancing age. Cerebral pulsatility represents a marker of vascular function that quantifies fluctuations in blood flow within each cardiac cycle in the cerebral arteries. Increases in cerebral pulsatility may contribute to structural damage in the brain such as white matter hyperintensities (WMH). Additionally, biological sex differences are apparent in brain vascular function and Alzheimer’s disease risk. As such, this research aimed to determine associations between cerebral pulsatility and WMH and evaluate the influence of sex. This research tested the hypothesis that elevated cerebral pulsatility is associated with higher WMH, and that the associations are sex‐specific.Method407 cognitively healthy middle‐aged and older adults (45‐87 years of age; 271 females) completed magnetic resonance imaging (MRI) performed on a 3T MRI scanner. WMH volumes were evaluated from T2 fluid‐attenuated inversion retention (FLAIR) images, while cerebral pulsatility index (PI) was evaluated in multiple intracranial arteries from 4D flow MRI. WMH fraction was calculated as the cubic root of WMH volume relative to intracranial volume.ResultPI in the vertebral arteries (VA) and basilar artery was positively associated with WMH fraction in females only (all female P≤0.01, all male P≥0.20). In contrast, PI in the internal carotid arteries (ICA) and middle cerebral arteries (MCA) was positively associated with WMH fraction in both sexes (all P≤0.01). However, the relationship between WMH fraction and PI in the MCA differed by sex such that the slope of the relationship was stronger in males than females (all P≤0.03). For example, higher right MCA PI was associated with greater WMH fraction in males (β = 0.39±0.09 a.u., R2 = 0.13) compared with females (β = 0.18±0.05 a.u., R2 = 0.05).ConclusionThese data suggest that, among cognitively healthy middle‐aged and older adults, elevated cerebral pulsatility is linked to greater WMH. However, the associations are sex‐ and vessel‐specific which may contribute to sex‐specific trajectories in Alzheimer’s disease with advancing age. The present results support the idea that elevated cerebral pulsatility contributes to structural alterations in the brain and thus reducing cerebral pulsatility may represent a promising target for mitigating cognitive decline.
Investigating cognitive performance of healthy older adults using phase synchrony analyses of EEG signals
Authors: Nemati Samaneh , Newman‐Norlund Roger , Newman‐Norlund Sarah , Fridriksson Julius 
Published: December 2023

AbstractBackgroundAging is a physiological process considered as a major risk factor for most irreversible neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Moreover, it is highly associated with decline in attention, memory, communication skills and many other cognitive functions as well as an overall delay in cognitive information processing in aging individuals free of any neurodegenerative diseases. Although much research has been done on the human brain in clinical cohorts, fewer studies have investigated the impact of age in healthy aging individuals. However, results of neuroimaging studies indicate that healthy aging is accompanied by significant structural and functional changes in the brain. This study uses EEG coherence and phase synchrony measures to investigate the relationship between the neural connectivity in the human brain and cognitive scores from the Montreal Cognitive Assessment (MoCA) in healthy older adults.Method75 participants aged between 60‐80 (M = 66.78, SD = 6.98) were recruited as part of the Aging Brain Cohort dataset at the University of South Carolina (ABC@UofSC). Resting‐state EEG signals were recorded from 128 electrodes using the Brain Vision actiCAP slim electrode layout with 500 Hz sampling frequency rate while participants were sitting quietly in a room using the Acti‐CHAMP EEG plus system. After preprocessing and denoising EEG signals, phase synchrony measure between each pair of electrodes was calculated for all frequency bands (delta, theta, alpha, gamma). Finally, a univariate general linear model (GLM) analysis was used to identify significant relationships between resting‐state functional connectivity indexed by phase synchrony and cognitive scores assessed by MoCA test while controlling for participants’ chronological age and gender.ResultsOur preliminary results revealed a significant association between cognitive scores and resting‐state functional connectivity of several brain electrodes in frontal, temporal, and parietal areas in high frequency alpha and beta bands.ConclusionOur results provide evidence that phase synchrony, a statistical measure of correlation between signals from electrodes spatially separated on the human scalp, could provide reliable biomarkers of cognitive performance of individuals in pre‐clinical disease states. This could enhance the clinicians’ ability to make early diagnosis of cognitive decline in older adults.
Snapshot of utilization of mobile research units for community screening with an emphasis in reaching previously underserved and underrepresented communities strategically across Central Florida
Authors: Cassidy Stephanie , Torres Sandra , Baez‐Torres Sheila , Lenox Brandon , Stanton Sean 
Published: December 2023

AbstractBackgroundIncreasing diversity in clinical trials requires intentionality and strategic planning. Traditional recruitment methods do not address barriers resulting in statistics supporting the majority of clinical trial participants being Caucasian, Non‐Hispanic males1. Identified barriers for these diverse populations in research include lack of knowledge on clinical trials, transportation, language and trust2.Effective methods to reach diverse communities require an “out of the box” thinking, intentionality, and creativity. By utilizing a Mobile Research Unit and bringing research to participants, sites are able to breakdown some of these barriers to better serve historically underserved and underrepresented populations.MethodA Mobile Research Unit was utilized in underserved and underrepresented areas which the site had built rapport with. During the time the Mobile Research Unit is in use, site staff engaged with the community by educating participants and by doing a hands‐on meaningful activity. Memory and/or blood base biomarkers were administered to patients who qualified.Result171 participants were screened for studies over a period of 4 months utilizing a mobile research unit. 42% of those screened are from diverse populations. 59% of those who screened were identified to be at risk and eligible for further screening.ConclusionBy breaking down some of the identified barriers, K2 was able to achieve better outcomes than what is typically seen in research of diverse populations. Utilizing the Mobile Research Unit and bringing research to participants allowed K2 to strengthen community connections and take some of the burden off participants. K2 will continue to support initiatives in enrolling diverse populations and employing tactics learned while supporting the Mobile Research Unit.
References:1. Ma, M. A., Gutiérrez, D. E., Frausto, J. M., & Al‐Delaimy, W. K. (2021). Minority representation in clinical trials in the United States. Mayo Clinic Proceedings, 96(1), 264‐266. https://doi.org/10.1016/j.mayocp.2020.10.0272. Luther T. Clark, Laurence Watkins, Ileana L. Piña, Mary Elmer, Ola Akinboboye, Millicent Gorham, Brenda Jamerson, Cassandra McCullough, Christine Pierre, Adam B. Polis, Gary Puckrein, Jeanne M. Regnante, Increasing Diversity in Clinical Trials: Overcoming Critical Barriers, Current Problems in Cardiology, Volume 44, Issue 5, 2019, Pages 148‐172, ISSN 0146‐2806, https://doi.org/10.1016/j.cpcardiol.2018.11.002.