bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Recruitment Sources in a Multicenter Clinical Trial for Dementia Prevention ‐ rrAD study
Authors: Hall Tristyn , Szabo‐Reed Amanda , Van Sciver Angela R , Truver Bryce , Goff Sara , Sewell Monica , Martin Adriana , Vidoni Eric , Burns Jeffrey M. , Keller Jeffrey N. , Binder Ellen F. , Zhang Rong 
Published: December 2023

AbstractBackgroundExercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD Study) was a NIH‐funded multisite, clinical trial. The rrAD Study assesses the effects of aerobic exercise training and intensive pharmacological reduction of vascular risk factors on cognitive performance in older adults at high risk for Alzheimer’s disease (AD). The enrollment goal was 640 participants across the span of two years. We report herein our recruitment and enrollment results of the rrAD Study.MethodThe major inclusion criteria were older adults, age 60‐85, who had family history (FH) of dementia or subjective memory complaints, hypertension, and a sedentary lifestyle. Individuals with dementia and other neurodegenerative diseases, or unstable medical conditions were excluded (NCT02913664). 3,291 potential participants were recruited and 2,747 were phone screened to participate in the rrAD Study. 513 cognitively normal older adults, aged 60 to 85 years with hypertension and increased risk for AD were randomized.ResultThe rrAD Study had a 15.5% recruitment yield of total phone screened individuals to randomization. E‐mail brought in the largest number of phone screen contacts and was the overall most cited recruitment source (20.9%, n = 574, Figure 1), followed by interviews/editorials (18.7%, n = 515), other/unknown source (17.9%, n = 492), and broadcast advertising (11.8%, n = 325). E‐mail and interview/editorials led to greatest number of consented and randomized participants. However, the recruitment sources that were more likely to lead to consent/participation were, professional referral (i.e. physician, 57.1% yield), social media (49.2% yield), and mail/phone from site (45.2% yield).ConclusionFrom this outreach, the utilization of multiple recruitment sources prove to be a dominant factor to meet recruitment and enrollment goals. E‐mail and interview/editorials demonstrate to be the most effective recruitment sources that led to the greatest number of phone screens, consents, and randomizations. In future studies, we might limit the broadcast advertisement effort since it did not lead to a high volume of consents and randomization; this could be due to the limited amount of study information stated on a 60‐second radio advertisement. Whereas, e‐mail and interview/editorials may produce more qualified participants since these sources can provide a wide scope and detailed information about the study.
Communication for Alzheimer’s treatment success in healthcare interventions with education
Authors: Swenson Danielle E , Garfield Lindsey , Carroll Candace 
Published: December 2023

AbstractBackgroundThe CDC estimates that 5.8 million Americans will be diagnosed with Alzheimer’s disease in 2020, and the number of Alzheimer’s cases is projected to nearly triple to 14 million people by 2060 (Matthews et al., 2019). Alzheimer’s patients frequently have difficulty communicating with healthcare providers resulting in decreased quality of care. Family members of Alzheimer’s patients accompany their loved ones to healthcare appointments, frequently witnessing an escalation of confusion and not possessing the knowledge and tools to aid communication (Thompson et al., 2020). Currently, in assisted living programs for Alzheimer’s patients, family members are not educated on communication strategies when leaving the facility with their loved ones (Brodaty & Donkin, 2009. Therefore the purpose of this project is to develop an Alzheimer’s educational intervention on communication for family members of patients with Alzheimer’s currently living in an assisted living program.MethodParticipants will include family members of Alzheimer’s patients from an assisted living unit at a senior facility in the Midwest United States. A zoom educational presentation will include how family members can assist their loved ones with Alzheimer’s disease during healthcare/dentist visits, and personal trips such as hair salons, and restaurants. Participants will complete pre‐ and post‐test evaluations of their knowledge regarding best communication practices for loved ones with Alzheimer’s and their confidence in their ability to apply these methodsResultWe will assess the impact of this project and its implications as a nurse‐driven education to improve family members' knowledge related to Alzheimer’s communication. This can improve outings and experiences for families, ultimately resulting in improved quality of life for Alzheimer’s patients.ConclusionAlzheimer’s disease education is needed for family members to help navigate common appointments and outings such as healthcare/dentist visits, hygienic/hair salon appointments, and restaurants. This education can improve the quality of life for Alzheimer’s patients and their family members.
Multiomics‐based prediction of trajectories of global cognitive functioning in the ADNI cohort
Authors: Laroche Valentin , Reijnders Rick A , Harvey Joshua , Jansen Willemijn J. , Eijssen Lars M.T. , Cavill Rachel , Lunnon Katie , van den Hove Daniel L.A. , Pishva Ehsan 
Published: December 2023

AbstractBackgroundCognitive impairment is the first manifestation of dementia. However, the rate of changes in cognitive function varies between individuals and unraveling heterogeneity in the trajectory of cognitive decline and dementia is crucial for adopting a suitable treatment. In this study, first, we aimed at identifying distinct trajectories of cognitive function, and next we used extensive machine learning approaches on multi‐trait ploygenic scores,CSF proteomics, plasma lipidomics and metabolomics data for classification of the trajectories identified in the initial analysis.MethodThree‐year trajectories of global cognitive functioning were defined using six longitudinal measurements of the Mini‐Mental State Examination (MMSE) on 640 individuals in the Alzheimer’s disease Neuroimaging Initiative (ADNI) cohort. To compute the trajectories of cognitive function, we applied Latent Class Mixed Modeling adjusted for age, sex, and education. We used multiple machine learning algorithms, including Random Forest, Conditional Random Forest, Generalized Linear Models, and (sparse) Partial Least Square Discriminant Analysis. The best performing models were selected based on a set of prediction performance metrics.ResultWe identified three distinct trajectories of global cognitive function: Stable, Slow decline (SD) and Fast Decline (FD). The Random Forest algorithm performed best in prediction of the Stable versus Decliners (SD + FD), using the combined omics data. (AUC: 0.83 and a Matthews Correlation Coefficient (MCC): 0.59). The model is based on seven molecular features, among which we found lipids belonging to the ceramide pathway which has already been implicated in cognitive impairment and AD.ConclusionDefining trajectories of individuals with distinct patterns of cognitive changes over time, paired with omics‐based data, will allow the identification of new biomarkers for early detection of dementia. Additionally, they might unveil novel subtype‐specific molecular pathways which can contribute to more precise drug discovery processes.
Lower Physical Activity Is Associated With Objective But Not Subjective Cognitive Impairment In Older Adults Without Dementia
Authors: Alonzo Matthew , Ringman John M , Schneider Lon S. S. , Braskie Meredith N , Toga Arthur W. , Zlokovic Berislav V , Chui Helena C , Joe Elizabeth B 
Published: December 2023

AbstractBackgroundPhysical activity has been associated with better performance on cognitive assessments for older adults in both observational and interventional studies. Older adults who exercise the 150 minutes a week recommended by the Physical Activity Guidelines for Americans were also less likely to report subjective cognitive decline on the Behavioral Risk Factor Surveillance System than those with lower levels of physical activity. Potential explanations for a cognitive benefit from exercise include reduction of vascular risk factors, preservation of brain mass and neuronal structural integrity, and promotion of psychological health and self‐efficacy.MethodCross‐sectional data on exercise habits, self‐reported memory problems, and cognition were collected for 137 older adults without dementia as part of a larger observational study. Participants were categorized as meeting (3 or more hours a week of physical activity) or not meeting (< 3 hours) physical activity recommendations. We used multivariable logistic regression to evaluate the association between exercise and self‐reported memory problem, and linear regression for association between exercise and total score on the Montreal Cognitive Assessment (MoCA) after adjusting for potential confounders including age, sex, level of education, cognitive status (CDR global score of 0 vs 0.5), and Geriatric Depression Scale score.ResultData on baseline exercise was available for 103 cognitively normal older adults and 34 with mild cognitive impairment (MCI). Mean participant age was 66.6 years and 58.4% were female. 48 participants (35%) reported exercising at least 3 hours per week. Participants with at least 3 hours a week of physical activity had significantly higher scores on the MoCA compared with those with less than 3 hours a week (B = 1.22, p = 0.040) after adjusting for age, sex, level of education, cognitive status, and depressive symptoms. There was no association between physical activity and participant‐reported memory symptoms using the same covariates (B = ‐0.50, p = 0.223).ConclusionWeekly physical activity levels consistent with current guidelines were associated with better performance on a cognitive assessment in older adults without dementia. Physical activity was not associated with presence or absence of a self‐reported memory problem in this sample.
Identification of novel genetic risk factors for cerebral amyloid angiopathy and characterization of the implicated LINC‐PINT locus
Authors: Atik Merve , Reddy Joseph S. , Nguyen Thuy , Sotelo Katie , Tutor‐New Frederick Q , Carrasquillo Minerva M. , DeTure Michael , Dickson Dennis W. , Allen Mariet , Ertekin‐Taner Nilufer 
Published: December 2023

AbstractBackgroundCerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid‐beta in the cerebrovasculature, effects blood vessel integrity leading to brain hemorrhages and an accelerated cognitive decline in Alzheimer’s disease (AD) patients. In a previous genome‐wide association study (GWAS) of 853 neuropathologically confirmed AD cases, we identified a LINC‐PINT splice variant that associated with lower CAA levels amongst individuals that did not have a copy of the APOEe4 AD risk allele (Reddy. J et al 2021). In this study, we perform GWAS to identify further genetic risk factors for CAA and AD neuropathology (Braak stage, Thal phase) in additional AD cases, and participants lacking significant AD pathology (non‐AD).MethodWe expanded the original AD cohort (N = 853) with 400 additional AD cases genotyped using the Infinium Omni2.5+Exome array. We also identified 110 AD and 502 non‐AD donors from the Mayo Clinic Brain Bank, with existing CAA scores and genome‐wide genotypes. We performed QC and imputation of these genotypes to TOPMed. We will conduct GWAS in AD only (N = 1,363), non‐AD only, as well as the combined cohort (N = 1,865). We will test imputed variant dosages for association with square root transformed CAA, Braak and Thal, using linear regression in PLINK, adjusting for relevant covariates. We will perform interaction analysis of CAA‐associated variants with APOEe4 and sex; and pursue stratified analyses. Summary statistics will be utilized to perform SNP‐based gene set enrichment analysis to identify biological pathways implicated in CAA.ResultWe expect that the increased power of this expanded dataset will lead to the identification of additional novel genetic risk factors for CAA and AD neuropathology. Genetic interaction analysis with sex and APOEe4 may further elucidate the role of these risk factors. The addition of 1,102 participants will enable assessment of the LINC‐PINT locus for association with CAA in an independent dataset.ConclusionWe expect this study will provide further insights into the genetic architecture underlying risk for CAA, both in the context of significant AD pathology, and without. Characterization of genetic variants in the context of neuropathology may lead to new avenues of research aimed at identifying biomarkers and therapies to treat CAA, and AD.
Advocating for Change: Lessons Learned from Ontario’s Quest for a Renewed Dementia Strategy
Authors: Fitzgerald Kyle , Paron Shawn 
Published: December 2023

AbstractDementia has been labelled a public health priority by the WHO; with prevalence expected to triple over the next 30 years, urgent, whole‐of‐government action is needed to prepare for unprecedented strains on our health, home, and long‐term care systems. This session will focus on the experiences of Ontario, Canada’s largest province, detailing how government, private, and not‐for‐profit stakeholders can collaborate to influence policy.The effectiveness of policy networks as a tool to create policy change, specifically in the dementia space, will be examined using Ontario as an example. Learning outcomes will include a better understanding of how public institutions make decisions, what guides a policy agenda and how to influence such, how to create a sense of urgency, defining ageing as a problem worthy of public consideration, and evaluating the success of advocacy efforts. Participants will be encouraged to consider networks they can join and/or form in their respective jurisdictions, and how they can contribute personally and/or professionally to advocacy efforts.Examples of successful advocacy initiatives in Ontario will be examined. These include public campaigns leading up to and during the 2022 Ontario general election; the Roadmap Towards a Renewed Ontario Dementia Strategy (www.alzheimer.ca/on/roadmap); and the Ontario Dementia Care Alliance (https://alzheimer.ca/on/en/take‐action/policy‐advocacy/ontario‐dementia‐care‐alliance).
Dementia with Lewy bodies Drug Therapies in Clinical Trials: 2022
Authors: Abdelnour Carla , Gonzalez Maria Camila , Gibson Lucy L , Poston Kathleen L. , Ballard Clive G , Cummings Jeffrey L. , Aarsland Dag 
Published: December 2023

AbstractBackgroundReviews of randomized clinical trials (RCTs) in Dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease‐modifying therapies (DMTs).MethodsWe performed a Systematic Review of DLB drug development by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB. We analyzed recruitment status, the disease stage and diagnostic groups included in clinical trials, number of trials participants and treatment exposure, use of repurposed agents per clinical trial phase, description of outcome measures for primary endpoints, use of biomarkers for inclusion and/or outcome measures, sponsorship, and global distribution.ResultsWe found 25 agents in 40 trials assessing symptomatic treatments and disease modifying therapies for DLB: 7 Phase 3, 31 Phase 2, and 2 Phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend towards including participants at the prodromal stages, although more than half of active clinical trials will enroll mild to moderate dementia patients. Additionally, repurposed agents are frequently tested representing 65% of clinical trials.ConclusionTo accelerate DLB drug development there is a need for more clinical trials, increased diagnosis at earlier stages of the disease, disease‐specific outcome measures and biomarkers, as well as augmenting global representation and including more diverse populations.
Tasmanian ISLAND Sleep Study: prodromal neurodegenerative disease (iRBD) is associated with subjective reports of daytime sleepiness and poor sleep quality
Authors: Bramich Samantha , King Anna E , Noyce Alastair J , Bindoff Aidan D , Kuruvilla Maneesh , Naismith Sharon L , Bartlett Larissa , Vickers James C , Alty Jane E 
Published: December 2023

AbstractBackgroundIsolated REM sleep behaviour disorder (iRBD) is a prodrome to dementia with Lewy bodies (DLB) and other neurodegenerative disease (NDD) such that over 90% of people with iRBD (pwRBD) will develop a NDD within 10 years of diagnosis. Disrupted sleep and dream‐enactment episodes are frequently observed by bed partners of pwRBD but it is unclear whether pwRBD perceive reduced sleep quality themselves, as previous studies show inconsistent results. This research aims to investigate sleep quality in iRBD and we hypothesise that people with probable iRBD (pwpRBD) will report poorer sleep quality, compared to healthy controls.MethodAdults aged 50+ years in the Tasmanian ISLAND Sleep Study, Australia, completed the single REM Sleep Behaviour Disorder Screening Question (RBD1Q) and the Pittsburgh Sleep Quality Index (PSQI) online. The PSQI includes a ‘total sleep quality’ score as well as 7 subscales: duration of sleep, sleep disturbance, sleep latency, day dysfunction due to sleepiness, sleep efficiency, overall sleep quality, and need meds to sleep.Result2,905 participants were recruited (mean (SD) age 64 (7.7) years; 26% male) and 273 (9.4%) screened positive for pRBD (45% male). In the pRBD group, 66% had poor total sleep quality, compared to 57% of controls (p = 0.001). pRBD was associated with a greater prevalence of sleep disturbance (67% vs 54%) and daytime dysfunction due to sleepiness (24% vs 11%). There was no difference in sleep duration, sleep latency, or sleep efficiency between pRBD and controls.ConclusionWe found that pwpRBD report more sleep disturbance, daytime sleepiness and overall poorer sleep quality compared to those without pRBD. This suggests that pwpRBD may suffer from greater sleepiness than has previously been reported in the literature and highlights the importance of sleep enquiries in those with suspected prodromal NDD who drive or operate machinery.
The Effect of Socialization on Alzheimer’s Disease
Authors: Khanna Deepesh , Maldonado‐Puebla Ricardo , Raina Parth 
Published: December 2023

AbstractBackgroundAge is a risk factor for Alzheimer’s disease, a neurodegenerative disease where beta amyloid plaques accumulate in the brain1. Elderly individuals especially those in nursing homes were burdened by the social isolation during the COVID‐19 pandemic. The purpose of this literature review is to describe the effectiveness of social engagement and how combatting isolation can have a neuroprotective effect in individuals at risk for Alzheimer’s disease.MethodWe conducted a search in PubMed examining articles from 2010 to 2023 that discussed the effect of socialization on Alzheimer’s disease particularly during the COVID‐19 pandemic. Our search terms were “Alzheimer’s Disease + Socialization”, “Social Isolation + Alzheimer’s Disease”, “Alzheimer’s Disease + COVID‐19”, “COVID‐19 + Social Isolation”, “Social Interventions + Alzheimer’s Disease”. Inclusion criteria consisted of patients ages 60 and older with Alzheimer’s disease, mention of social isolation or engagement, and any relationship between COVID‐19 and Alzheimer’s disease. Exclusion criteria were defined as other dementias, non‐social interventions, and the effects of other viruses on Alzheimer’s disease. After the screening process 30 articles were included along with 6 articles that were suitable to the topic.ResultOf the 36 total articles: 19 articles focused on an intervention involving socialization; 8 articles explored the effect of social isolation during COVID‐19 on patients with Alzheimer’s disease; 5 articles examined social isolation as a risk factor for dementia; and 4 articles discussed the effect of socialization on Alzheimer’s disease. A few studies reported that having a large social network can improve cognition and mood for patients with Alzheimer’s disease. Studies reported that interventions such as volunteering, video calls, group art classes, animal interactions, and others produced positive outcomes in Alzheimer’s patients but not all were statistically significant.ConclusionOur review found a consistent association between a socially integrated lifestyle and decreased incidence of early‐onset dementia. Although not all interventions were solely social, the presence of a strong social structure remained at the core of a healthy aging process.References:1. Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019). Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. International journal of nanomedicine, 14, 5541‐5554. https://doi.org/10.2147/IJN.S200490
Comparing longitudinal impact of LATE and Alzheimer’s neuropathologic changes in the oldest old
Authors: Sajjadi S. Ahmad , Yu Jiaxin , Qian Tianchen , Bukhari Syed A. , Montine Thomas J. , Corrada María M. M. , Kawas Claudia H. 
Published: December 2023

AbstractBackgroundLimbic predominant age related TDP‐43 encephalopathy‐neuropathologic change (LATE‐NC) is prevalent in the oldest old and clinically, it mimics Alzheimer’s disease. Our aim was to determine the association between longitudinal change in clinical and neuropsychological measures and the common neurodegenerative diseases in an exclusively oldest‐old cohort to establish features that help distinguish LATE‐NC from Alzheimer disease neuropathologic change (ADNC) during life.Method412 participants from The 90+ Study with longitudinal evaluations and autopsy data were studied. We dichotomized the neuropathologic features and considered the following as the criteria for presence: any degree (mild, moderate or severe) of LATE‐NC, cerebral amyloid angiopathy (CAA), arteriolosclerosis, and hippocampal sclerosis; moderate or severe likelihood of ADNC (according to NIA‐AA criteria); limbic, transitional, or neocortical Lewy bodies (LB); two or more microvascular lesions (MVLs); and severe atherosclerosis. Longitudinal scores of Clinical Dementia Rating Sum of the Boxes (CDR‐SB) and 13 neuropsychological tests grouped into 7 cognitive domains were standardized. We studied the longitudinal relationship between CDR‐SB and each of the 7 cognitive domains with the neuropathologic changes using linear mixed effect models that included all neuropathologic changes adjusting for age at death, sex, and education. P‐values were corrected for multiple comparisons.ResultTable 1 summarizes the characteristics of the participants. LATE‐NC was present in 36% of the cohort and 51% of those who died with dementia. Figure 1 demonstrates the association of pathologic features with CDR‐SB and cognitive outcomes in a model that included all pathologies and was adjusted for multiple comparisons. At time of death, both LATE‐NC and ADNC were associated with worse performance in CDR‐SB, global cognition, memory, language, and orientation. Longitudinally, out of the two diseases, only LATE‐NC was associated with significant decline in CDR‐SB and orientation, and neither were associated with significant longitudinal decline in other cognitive domains including memory.ConclusionOur results confirm the high prevalence and important cognitive consequences of LATE‐NC in the oldest old. Remarkable similarity of cognitive signature of LATE‐NC and ADNC highlight the need for biomarkers capable of distinguishing these two consequential diseases of the oldest old.