bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fully remote Parkinson’s disease study served by mobile research nurses
Authors: Gerken‐Booco Alicia 
Published: December 2023

AbstractBackgroundBecause Parkinson’s disease is a progressive brain disorder that leads to shaking and stiffness, eventually causing difficulty with walking, balance and coordination, patients are at very high risk of fractures from multiple and sometimes severe falls. Researchers are studying whether zoledronic acid, approved by the FDA to treat osteoporosis by increasing bone strength, will reduce fractures in people with Parkinson’s disease.MethodThe TOPAZ trial seeks to enroll 3,500 participants over the age of 60, making it the largest double‐blind, placebo‐controlled, randomized, fully decentralized clinical trial ever attempted in people with parkinsonism. Due to the mobility constraints of the study population, it is necessary to design a study that can recruit a large number of participants from across a wide geography and develop a multi‐step protocol that can be done entirely from participants’ homes. The study recruitment began October 1, 2020 and is expected to be completed within three years. To date, 1807 participants have been enrolled.ResultThe patient‐centric nature of the study enabled participant recruitment from a broad geographic area to enhance diversity and be more representative of “real world” patients. The study is achieving an estimated cost savings of 80% per participant compared with a similar trial conducted in a clinical site due to lower overhead and the fact that a home‐based study forces researchers to engage only in those activities necessary for the study.ConclusionMobile research nurses are necessary for certain studies, including those involving a large number of patients with a disabling disease. Due to the limited mobility of many of the participants in this study and the need to enroll so many patients, the only way this trial is possible is by using decentralized clinical trial methods including mobile research nurses. This study illustrates the many advantages of home‐based clinical trials, including: increased convenience for patients; larger number of study participants; potential for increased diversity in clinical trial participation; and reduced study costs.References:1. Tanner, Caroline M., et al. “The TOPAZ study: a home‐based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism.” NPJ Parkinson’s disease 7.1 (2021): 1‐6.
Six Year Effects of Hearing Treatment on Cognitive Decline and Dementia: Design and Statistical Considerations of the Aging and Cognitive Health Evaluation in Elders – Brain Health Follow‐Up Study
Authors: Huang Alison R , Pike James R. , Arnold Michelle L , Burgard Sheila , Chisolm Theresa , Couper David , Deal Jennifer A , Goman Adele M , Gravens‐Mueller Lisa , Hayden Kathleen M. , Jack Clifford R. , Mitchelle Christine , Mosley Thomas H. , Pankow James , Reed Nicholas S , Sanchez Victoria A , Schrack Jennifer A , Coresh Josef , Lin Frank R ,   for the ACHIEVE Collaborative Research Group
Published: December 2023

AbstractBackgroundHearing loss is associated with cognitive decline and dementia. The ongoing ACHIEVE Study was the first randomized trial to test the effects of hearing treatment on three‐year cognitive change. The ACHIEVE – Brain Health Follow‐Up Study will extend follow‐up to six years post‐randomization to determine the long‐term and potentially nonlinear effects of hearing treatment vs. health education control with delayed treatment on dementia and cognitive decline.MethodsParticipants will be recruited from the 977 participants enrolled in the ACHIEVE Study. After Year 3, hearing intervention participants will continue to receive hearing care and the control group will be offered the hearing intervention. Co‐primary study outcomes will be cognitive decline and a composite of incident mild cognitive impairment (MCI)/probable dementia. Secondary outcomes include domain‐specific cognitive decline, brain structural changes on magnetic resonance imaging (MRI), and other functional outcomes (e.g., physical activity, social isolation). Power analyses for the co‐primary outcomes assumed an annual attrition rate of 10% and an immediate, lagged, or cumulative treatment effect.ResultsWhen comparing multi‐year cognitive decline (Table 1), in the scenario of a constant treatment effect that assumes a strong and immediate treatment effect, the benefit of extended follow‐up is not greater power, but additional information on the long‐term effects of hearing intervention. In a scenario of a lagged treatment effect, a two‐year lag in the treatment effect causes the Year 3 assessment to be severely underpowered (28%) but provides sufficient power (80%) at Year 6 despite attrition. In a scenario of a cumulative treatment effect that increases with time, analyses are similarly underpowered at Year 3 (65%) but not at Year 6 (82%). The same pattern is evident when estimating the power at Year 3 (57%) and Year 6 (80%) to detect incident MCI/probable dementia in a Cox regression model that assumes a protective hazard ratio of 0.70 (Figure 1).ConclusionAcross all non‐constant scenarios of potential treatment effect, six years of follow‐up increases precision and provides valuable information to better delineate long‐term cognitive trajectories. The ACHIEVE ‐ Brain Health Follow‐Up Study will be completed in 2025.
Development and validation of a caregiver‐reported outcome measure for Alzheimer’s disease: the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI), a fully validated tool to bolster clinical trial and research infrastructure
Authors: Rosero Spencer , Varma Anika , Seabury Jamison , Weinstein Jennifer , Engebrecht Charlotte , Dilek Nuran , Arky Abigail , Santos Elizabeth , Heatwole Chad 
Published: December 2023

AbstractBackgroundAs therapeutic advancements are made in the field of Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), it is important to have a fully validated, sensitive, and reliable, disease‐specific outcome measures that can accurately measure changes in AD and MCI symptomatic disease burden. The U.S. Food and Drug Administration has encouraged the use of caregiver reported outcome measures (CRO) to measure therapeutic benefit of new treatments on patient populations when a patient is unable to report on themselves. This research describes the creation, testing, and validation of a novel, multifactorial CRO: The Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI).MethodsWe conducted interviews and a large cross‐sectional study involving individuals with AD and MCI and their caregivers to determine what symptoms and issues are most important to patients (Figure 1). Questions were selected for the ADCR‐HI based on their importance to patients with MCI and AD, potential to respond to therapeutic intervention, and generalizability. We beta tested the ADCR‐HI with caregivers of individuals with MCI and AD to determine its clarity, ease of use, and relevance to those with MCI and AD. We performed test‐retest reliability, known groups validity, internal consistency, and area under the curve analyses of the ADCR‐HI to assess the statistical characteristics, performance, and clinical meaningfulness of the outcome measure.ResultsThe content of the ADCR‐HI was validated using a cross‐sectional study of 329 caregivers. The ADCR‐HI contains 8 subscales that measure disease burden in the following areas: 1. Memory, 2. Cognitive health, 3. Social Health, 4. Physical Health, 5. Communication, 6. Fatigue, 7. Sleep, and 8. Emotional Health. The ADCR‐HI was identified as easy to use, relevant to the patient population, responsive, and clear during beta testing. The ADCR‐HI was shown to be reliable during test‐retest reliability testing with 34 caregivers and able to distinguish between patient cohorts with different disease severities.ConclusionThe ADCR‐HI is a valid, sensitive, and reliable marker of disease burden in AD. This disease‐specific outcome measure is available for use by researchers, clinicians, patient organizations, and companies to measure changes in disease burden during therapeutic trials.
In vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in frontotemporal degeneration and corticobasal syndrome.
Authors: Lagarde Julien , Olivieri Pauline , Tonietto Matteo , Lehéricy Stéphane , Moussion Martin , Caillé Fabien , Gervais Philippe , Bottlaender Michel , Sarazin Marie 
Published: December 2023

AbstractBackgroundNeuropathological studies have shown alterations in both locus coeruleus (LC) and basal forebrain in frontotemporal degeneration (FTD) and corticobasal syndrome (CBS) particularly in progressive supranuclear palsy (PSP). We aimed to investigate in vivo the LC and nucleus basalis of Meynert (NBM) integrity in patients with FTD and CBS.MethodWe compared the LC signal intensity (LC‐I), which reflects the LC integrity, and the NBM volume on 3T MRI in i) FTD patients (n = 17) ii) CBS patients (n = 8;) iii) prodromal/mild AD (n = 34) and iv) amyloid‐negative controls (n = 15). PiB‐PET and/or AD CSF biomarkers were negative in all FTD and CBS patients, and positive in all AD patients. All subjects underwent a complete neuropsychological assessment and 3T brain MRI performed on the same scan. The four groups were age‐matched. The MMSE score did not differ significantly between the 3 groups of patients.ResultCompared to controls, LC‐I and NBM volume were significantly decreased in FTD (p = 0.05 and 0.00015, respectively) and AD patients (p = 0.0005 and 0.002, respectively). LC‐I and NBM volume were also decreased in CBS in comparison with controls but the difference was not statistically significant. In addition, we found no statistically significant difference in LC‐I and NBM volume between the three groups of patients. We observed no correlation between LC‐I or NBM volume and amyloid load, either when considering the whole group of patients or AD and FTD/CBS patients separately.ConclusionOur results are in line with neuropathological data and suggest that both cholinergic and noradrenergic systems are altered in AD and FTD. Post mortem data have suggested that, in FTD, both structures were more impaired in tau than in TDP‐43 proteinopathy, which cannot be explored in our study. In CBS, our results are less clear‐cut, probably due to the small sample size. Taken together, our data support the pathophysiological model in which both LC and NBM play a critical role not only in AD but also in other diseases and proteinopathies like FTD.
Review of Clinical Trials Showing the Efficacy of Memantine in Patients with Alzheimer’s Disease
Authors: Schuh Olivia , Khanna Deepesh 
Published: December 2023

AbstractBackgroundOver 6 million Americans suffer from Alzheimer’s disease (AD), a neurodegenerative disease characterized by changes in behavior, personality and progressive decline in cognitive function and memory. Therapies may slow the progression and aid in symptomatic relief of AD. One of these is Memantine, an N‐methyl‐D‐aspartate receptor antagonist. The objective of this review is to analyze clinical trials testing the efficacy of Memantine in the treatment of AD.MethodA search for clinical trials was conducted through clinicaltrials.gov with keywords search of “Alzheimer’s disease” and “United States” resulting in a total of 1592 clinical trials. Further inclusion criteria selected included; interventional clinical trial, with results, 65+, phase 4 which led to 23 clinical trials. Four of the 23 clinical trials were selected based upon their commonality of studying the efficacy of the drug Memantine in patients with AD.ResultA clinical trial studied whether Memantine (10mg BID) delayed the progression of driving impairment in participants with mild AD. In the group that received memantine, 100% of participants were able to pass the DriveABLE On‐Road Test at month 12 in contrast to an 83% passing rate in the placebo group. Another clinical trial reported improvements in the ratios of N‐acetylaspartate (NAA) to Creatine (Cr), NAA to choline (Cho), and NAA to myo‐inositol in comparison to baseline. Researchers analyzed the effects of implementing an individualized management program (IMP) and Memantine (10 mg BID) versus Memantine (10 mg BID) alone. Patients in the IMP and Memantine group markedly improved their Clinician Interview‐Based Assessment of Change Plus Caregiver Input Global Score while the Memantine group alone markedly got worse. Patients who took Memantine (10 mg BID) to assess the slowing of behavioral decline were reported to have improved caregiver assessment of behavioral disturbances while the placebo group did not show improvement.ConclusionMemantine may be effective in delaying the progression of driving impairment and behavioral decline. Implementing an IMP plus Memantine showed to have better outcomes than Memantine alone. None of these institutions provided data analysis to determine if data was significant.Reference: Medicine, U. S. N. L. o. (2023). “Clinicaltrials.gov.” Retrieved 01/23/2023, 2023, from https://clinicaltrials.gov/.
Disparities in Research Participation within a Multi‐Racial SARS‐CoV‐2 Cohort for Evaluation of Ultrahigh Field (7T) MRI and Clinical Precursors of Alzheimer’s Disease and Related Dementias
Authors: Vahidy Farhaan S , Hosseini Akram A. , Girard Timothy D. , Ibrahim Tamer , Jacobs Heidi I.L. , Roman Gustavo C , Masdeu Joseph C. , Li Karl , Garbarino Valentina R. , Goss Monica , Nair Rejani R , Patel Vibhuti N , Snyder Heather M , Tannous Jonika D , Snitz Beth E. , Ganguli Mary , Seshadri Sudha 
Published: December 2023

AbstractBackgroundThe COVID‐19 pandemic has disproportionately affected ethno‐racial minority populations and people with greater social deprivation. It is unknown whether such disparities influence research participation for investigations of long‐term neuro‐cognitive effects of SARS‐CoV‐2 infection.MethodAcross 3 US and 1 UK sites, we are enrolling a multi‐racial cohort of SARS‐CoV‐2 infected individuals and age, sex, race‐matched non‐infected controls. Utilizing harmonized protocols for cognitive assessments and 7‐Tesla MRI, we aim to provide ultra‐high‐field data on natural history of COVID‐19 driven microstructural and microvascular cerebral changes and associated cognitive trajectories. We will also compare the imaging markers to those observed in an existing cohort of early onset Alzheimer’s Disease and Related Dementias (ADRD). We analyzed screening and enrollment data to determine potential age, sex, race, ethnicity, and social deprivation disparities in research participation. We derived address‐based Area Deprivation Index (ADI) (scale 1 ‐10), with higher ADI indicating greater deprivation. Logistic regression models were fit to evaluate associates of non‐response and refusal. Odds Ratios (OR) and 95% confidence intervals (CI) are reported.ResultOver a 11‐month period, at a single US site, a total of 1,046 SARS‐CoV‐2 infected people and their controls were contacted, and 379 (36.2%) responded. In univariable analyses, non‐response was associated with younger age, male sex, non‐White race, and higher ADI (Table 1). In the fully adjusted model, non‐White race was independently associated with higher likelihood of non‐response [OR (CI) for Black vs. White: 1.49 (1.04, 2.12) and for Asian vs. White: 1.88 (1.28, 2.76)]., Independent of race, higher ADI was also associated with likelihood of non‐response (Table 2 and Figure 1). Among the responders, 228 (60.2%) refused. Although, no socio‐demographic factors were significantly associated with likelihood of refusal, the point estimates in the fully adjusted model suggest potential racial disparities in providing consent (Tables 1 and 2). Aggregated data from all sites will be presented.ConclusionIt is imperative to recognize and mitigate persistent disparities in the COVID‐19 pandemic, particularly pertaining to participation in long‐COVID research. Mechanisms of such persistent disparities need to be studied in context of cultures, beliefs, access, and clinical factors.
Bad questions: addressing non‐response and respondent feedback in a social and structural determinants of health (SSDoH) questionnaire
Authors: Stites Shana D. , Halberstadter Kimberly , Houston Jada Jeanette , Schumann Rosalie , Mechanic‐Hamilton Dawn 
Published: December 2023

AbstractBackgroundScientists must be able to characterize and measure social and structural determinants of health (SSDoH) in order to study their influences on Alzheimer’s disease and related dementias outcomes. Constructing measures that capture this heterogeneity is challenging. We summarize SSDoH questions that participants skipped and critiqued and our response.MethodAn online survey of 225 items capturing SSDoH was administered to cognitively unimpaired participants (n = 135) in the UPenn Alzheimer’s Disease Research Center clinical cohort. Self‐report questionnaire categories were: (1) Education, (2) Occupation, (3) Economic Status and Strain, (4) Stressors and Subjective Stress, (6) Subjective Social Support and Status, and (7) Sociodemographic data, which included age, race, language, disability, neighborhood, sex, sexual orientation, and gender identity questions. We summarize pilot data on item and instrument completion rates, participant feedback, and survey revisions to address participant critiques.ResultThe response and completion rates were 66% and 95% respectively. Most often skipped items were: mother’s highest education level (17% skipped), number of years attending a segregated school for those who did attend (15% skipped), childhood zip‐code (14% skipped), transportation mode around one’s neighborhood (13% skipped), and current worldview compared to during childhood (12% skipped). Few participants (n = 5/135) reported dislike or discomfort with any questions, with 3 of the 5 citing that questions about childhood caused discomfort. Participants also critiqued questions about education for not capturing their individual schooling experiences. In response to feedback, we conducted follow‐up discussions with participants about their reactions to specific childhood questions and expanded questions to capture more educational pathways, including trade school experiences and apprenticeships. We also added answer choices to often‐skipped items with insufficient answer options.ConclusionOverall, most SSDoH items had high completion rates, and few questions were consistently skipped by participants. While investigators often worry about offending or upsetting research participants, those in our study wanted to help improve questions. Participants acknowledged that some questions elicited strong emotions, but in most cases were both willing to complete these questions and appreciative of the chance to share their experiences. Designing questions that capture a fuller range of educational pathways was a valuable contribution to data collection.
Decay in Entorhinal White Matter/Gray Matter contrast in Alzheimer’s Disease Patients is reduced by 40Hz sensory stimulation
Authors: Da Xiao , Hempel Evan , Malchano Zach , Vaughan Brent , Megerian Jonathan Thomas , Hajos Mihaly , Cimenser Aylin 
Published: December 2023

AbstractBackgroundPrevious research has shown that white matter (WM) and gray matter (GM) tissues exhibit regionally selective pathological changes in Alzheimer’s disease (AD). The contrast between WM and GM signal intensities (WM/GM contrast) measured by magnetic resonance imaging (MRI) has previously been proposed as a method for quantifying these changes. It has been shown that WM/GM contrast can provide sensitive, independent, and distinct information about pathologies compared with traditional MRI measures. Studies have also shown, including entorhinal WM/GM contrast to traditional MRI measures resulted in better discrimination between AD and controls. We previously demonstrated that 40Hz auditory‐visual stimulation therapy reduced WM atrophy and myelin loss in AD patients. The present study quantified the effects of the therapy on the WM/GM contrast in the entorhinal region.MethodThis study used neuroimaging data from Overture, a phase I/II randomized, placebo‐controlled feasibility study (NCT03556280) in patients on the AD spectrum. Treatment group received 40Hz gamma sensory stimulation daily at home for six months, whereas placebo group received sham stimulation. Structural MRI was obtained at baseline, month 3 and month 6 visits using 1.5 Tesla scanner. FreeSurfer was used to process T1 MRI including entorhinal parcellation and cortical reconstructions for 38 participants (66% Treatment, 34% Placebo). For each vertex, WM signal intensity (WMI) is sampled at 1mm below, and GM signal intensity (GMI) is sampled at 30% of cortical thickness above the WM/GM border. WM/GM contrast was calculated as 100*(WMI–GMI)/(0.5*(WMI+GMI)) %. Bayesian linear mixed effects modeling was used to model changes in WM/GM contrast in the entorhinal region.ResultFollowing 6 months of treatment, we observed that the treatment group demonstrated 0.06±0.99% decrease and the placebo group demonstrated 1.26±1.04% decrease in WM/GM contrast (p<0.022).ConclusionWe found that six months of 40Hz gamma sensory therapy reduced the decline in WM/GM contrast in the entorhinal region. Since WM/GM contrast is associated with AD severity, and the entorhinal region is of particular interest in the early stages of AD, early intervention of the therapy may result in enhanced tissue preservation and reduced neurological damage.