bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): Harmonised Cognitive Assessment Protocol (HCAP) dress rehearsal review.
Authors: McAlinden Michael , Neville Charlotte , O'Hara Leeanne , Marr Calum , Langa Kenneth M , Ryan Lindsay H , Weir David R , McGuinness Bernadette 
Published: December 2023

AbstractBackgroundNICOLA, the largest public health cohort study of ageing in Northern Ireland, commenced in 2013 with a representative sample of ∼8500 individuals aged 50 years and over living across Northern Ireland.HCAP is a National Institute on Ageing (NIA) funded sub‐study designed to assess prevalence of cognitive impairment and dementia in a sample of 1000 participants aged 65 years and older.A dress rehearsal was carried out prior to the main study to implement the study as per the HCAP study protocol. This, ensured any issues could be identified prior to the main phase and the Standard Operating Procedures (SOP) could be amended accordingly.Method14 participant interviews and 14 informant interviews were completed between December 2021 and January 2022.The HCAP dress rehearsal sample was selected from the NICOLA research advisory panel, which included NICOLA participants and individuals from the charity group AgeNI.The study consisted of a face‐to‐face participant interview, comprising nineteen different measures of memory and thinking.During the informant interview a family member or friend was asked about participant’s ability to perform daily tasks and their social and cognitive activities.During the HCAP dress rehearsal, fieldwork staff conducted home visits in pairs: one conducting the interview while the other observed. Staff completed feedback forms which provided opportunities to comment on the use of computer software, consent processes and the administration of memory and thinking assessments.ResultSeveral areas for improvement were highlighted:Pre‐Visit Documentation: Fieldwork staff reflected on the complexities of test administration and the transition between computer and paper assessments. Pre‐visit protocols were revised to include preparation processes.Test Administration: Queries were raised on the logistics of test administration and scoring. These were resolved through contact with the Health and Retirement Study (HRS) team.Study Administration Processes: Additional administration databases were created and SOPs amended to ease the flow of recruitment and home visit bookings.ConclusionThe HCAP dress rehearsal highlighted the importance of pre‐visit preparation and staff training, combined with clear procedures and protocols to allow for the collection of high quality data and enhancement of the study experience for participants and researchers.
Underlying mechanisms, clinical manifestation, and methodological considerations of functional connectivity in Dementia with Lewy Bodies
Authors: Kucikova Ludmila , Kalabizadeh Hoda , Su Li 
Published: December 2023

AbstractBackgroundFunctional connectivity disturbances are potential disease mechanisms related to observable symptoms in Dementia with Lewy Bodies (DLB). Despite several existing theories, the exact relationship between functional connectivity, underlying mechanisms of the DLB, and symptomatology is yet not clear. The present review addresses this gap by summarising research findings of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) research while considering the impact of different methodological choices causing mixed findings.MethodWe performed a systematic literature review of resting‐state functional connectivity in DLB following PRISMA. We searched multiple databases from January 2000 to November 2022. Keywords included “DLB”, “connectivity”, “EEG”, and “fMRI”, their synonyms and acronyms, and related terms of network analysis. The final sample contained 6 EEG and 14 fMRI studies.ResultThe main methodological choices of fMRI articles included a data‐driven approach (i.e., Independent Component Analysis or Graph Theory; 43%), seed‐based or regions of interest (50%), or their combination (7%) with most studies focusing on large‐scale resting‐state networks (71%). The overall trend of connectivity findings showed a decrease, yet more subtle changes in the directionality of connectivity were observed when using a hypothesis‐driven approach (Fig 1A). The Default Mode Network (DMN) was the most studied network with 75% of relevant articles reporting decreased connectivity. Other networks with a consistent decrease in connectivity included Executive and Sensorimotor Networks (80% and 100% of relevant studies respectively). The inter‐network connectivity revealed the mixed relationship between the DMN, executive, attentional and visual networks (VN; Fig 1B). EEG studies showed a consistent decrease in connectivity on alpha and beta bands (100% and 66% of relevant studies respectively) and disorganisation in graph properties in regions overlapping with findings from large‐scale networks.ConclusionDysfunctions in large‐scale networks likely contribute to progressive degenerative mechanisms and are consistent with visual attention and perception processing theories of psychotic symptoms in the DLB. Hence, connectivity measures can capture brain disturbances in the DLB and remain crucial in uncovering underlying relationships between the networks’ disorganisation and disease mechanisms resulting in psychotic, motor, and cognitive symptoms in DLB. The choice of analytical approach might contribute to the directionality and mixed findings in the literature.
Retention of Study Partners in Longitudinal Studies of Alzheimer Disease
Authors: Edwards Dorothy F. 
Published: December 2023

AbstractBackgroundAlzheimer Disease Research Centers (ADRCs) require study partners (SPs) for all participants. SPs accompany participants to study visits, ensure protocol compliance and serve as informants for outcomes and adverse event reporting. Their attitudes and beliefs may therefore affect longitudinal data collection and retention for AD studies. However, little research has examined barriers and facilitators to SP participation in longitudinal AD investigations.ObjectiveA random sample of study partners (N = 212) of participants who had no or mild symptoms (global Clinical Dementia Rating [CDR]≤1) at four ADRCs were surveyed to examine facilitators and barriers to continued participation in AD studies.MethodsReasons for participation were analyzed with factor analysis and regression analysis. Effects of complaints and goal fulfillment on attendance were estimated with fractional logistic models.ResultsStudy partners most often participated in ADRC research for personal benefit and altruism. A majority of study partners rated ADRC participation as positive and meeting their goals. Although half reported at least one complaint, few regretted participating. When the participants had a CDR>0, spouse study partners (p<.01) and sibling study partners (p<.01) were more likely to emphasize personal benefits than were children of participants (p<.01) Spousal caregivers of participants with CDR>0, cited personal benefit as their primary motivation to participate while adult children of cognitively normal participants (CDR = 0) cited personal benefit. Respondents whose personal goals were met had fewer complaints and were more likely to have perfect attendance. More feedback about test results and study findings and better management of study visits were the most common recommendations.ConclusionStudy partners are motivated by both personal and altruistic goals. The salience of each goal depends on study partner type and the participant’s cognitive status. Fulfilling these goals may improve retention and reduce study partner complaints.
Effects of re‐training sessions in RUDAS assessment in a cohort of evaluators
Authors: Montesinos Rosa , Chambergo‐Michilot Diego , Unaucho‐Pilalumbo Maria M , Russo Griselda , Custodio Nilton 
Published: December 2023

AbstractBackgroundThe RUDAS scale has been widely used in cohorts and trials, nevertheless this tool is complex and there are no guidelines for using it. Since the RUDAS may be prone to mistakes, even when medical staff is trained once, we aimed to determine the number of correct assessments per each evaluator of a large cohort of adults regarding dementia risk factors after sessions of re‐training.MethodThis was a longitudinal study of 22 evaluators of a large study on dementia risk factors in Antofagaste (Chile) and Quito (Ecuador). Use of RUDAS was established in the study protocol, so all evaluators were trained once to use this tool before study initiation. In order to ensure accuracy between evaluators, they were scheduled for five video‐sessions of re‐training leaded by an expert Neurologist. This sessions lasted 2.5 hours and the aim was to identify mistakes and doubts when performing RUDAS. After each session evaluators had a written test. The content was a simulation of a typical dementia case to be assessed by RUDAS. We collected the number of correct answers by domain.ResultWe assessed the mean number of correct answers by domain and the changes from baseline to the fifth test (visuospatial orientation: 4.25 → 4.89, praxis: 0.25 → 1.05, visuo‐constructional drawing: 0.05 → 2.68, judgement: max. 1.8 → 3, memory recall: 0.2 → 0, language: 5.7 → 8). Re‐training had a significant increase of correct answers in all domains. Despite the majority showed an increase in score from baseline to the fifth test, the mean score in fifth test was higher than in the prior tests only in judgement, memory recall and visuo‐constructional drawing domains. In the other domains we found that the fourth test scored higher than the fifth one, nevertheless the difference was not clinically important.ConclusionTraining and re‐training are important steps in the approach and use of an assessment tool in trials and cohorts. RUDAS is a complex tool that may be prone to mistakes, therefore we recommend at least five sessions of re‐training to identify mistakes and doubts among evaluators.
Primer: MIND at Home Alzheimer’s and Dementia Care Coordination Program
Authors: Samus Quincy M 
Published: December 2023

AbstractBackgroundPeople living with dementia (PLWD) represent some of the highest‐need and highest‐cost individuals living in the community. The complexity and range of needs (including medical, behavioral, and social needs) make dementia one of the most expensive chronic conditions in the U.S., and a strong candidate for improving care and reducing costs through care management support.MethodThe Maximizing Independence (MIND) at Home dementia care program, developed and implemented in a variety of settings and contexts over the last 15 years, is an advanced care coordination program for community‐living persons with dementia and cognitive impairment and their informal caregiver. The program is delivered through an interdisciplinary, dementia capable collaborative team. Developed by researchers at Johns Hopkins University, the MIND program consists of a comprehensive set of assessments, tools and staff trainings designed to increase individual longevity in the home/community; reduce unmet care needs and improve quality of care; improve person‐centered outcomes; reduce costly acute health care utilization; and reduce caregiver burden.ResultThe MIND at Home program model builds on three prior trials (two RCTs, one quasi‐experimental design) of the MIND at Home dementia care coordination model. These have included a philanthropically‐funded parallel group randomized controlled single blind trial (RCT) (MIND‐RCT‐1 n = 303; 2007‐2012), an NIA‐funded RCT (MIND‐RCT‐2; n = 302; 2014‐2020), and a CMS Health Care Innovation Award Round 2 demonstration project (MIND‐HCIA; n = 342; 2014‐2018). The program has been embedded into 3 types of real world practice settings to date: managed care health plans, primary care, home health care.ConclusionThe research findings to date for in development of the MIND model show that community‐living older persons with dementia and cognitive impairment experience substantial unmet, yet modifiable care needs among community‐living PWD and caregivers, and that MIND at Home can benefit persons living with dementia and their family caregivers. Benefits include delay in transition from home and nursing home placement; reductions in use of acute and institutional care and total Medicaid spending; and improvement in care quality, behavior, and high program satisfaction. Individuals with lower income may benefit more.
Sex‐specific plasma markers of cholesterol‐metabolism and plant sterols predict cognitive decline in older people – a ten years follow‐up study
Authors: Spinedi Matteo , Lütjohann Dieter , Clark Christopher , Popp Julius 
Published: December 2023

AbstractBackgroundMultiple studies in clinical settings show that there is a link between a dysregulation of cholesterol metabolism and neurodegenerative pathologies and dementia. Diet‐based plant sterols may also interfere with neurodegeneration and cognitive decline through cholesterol‐lowering properties. In this study, we investigate whether circulating levels of cholesterol, its precursors, and metabolites, as well as triglycerides, and phytosterols predict cognitive decline ten years later in the general population. As a secondary objective we address the role of sex and the APOE genotype on these relationships.MethodWe considered 206 individuals aged 65 and older from a population‐based prospective study from Lausanne, Switzerland. A comprehensive cognitive assessment was performed at baseline and after ten years. We quantified the plasma levels of cholesterol, high‐density lipoprotein (HDL‐) cholesterol, triglyceride, cholesterol precursors (lathosterol, lanosterol, desmosterol, dihydrolanosterol), cholesterol derivatives (cholestanol), oxysterols (24S‐hydroxycholesterol [24S‐OHC], 7α‐hydroxycholesterol, 27‐hydroxycholesterol), and phytosterols (campesterol, campestanol, stigmasterol, sitosterol, sitostanol and brassicasterol) at baseline and after five years. Regression analysis (considering several possible confounder including APOE‐genotype) determined the relationship between baseline sterol levels, and their changes between baseline and five‐year follow‐up, with measures of cognitive decline (i.e. changes in Clinical Dementia Rating (CDR), Mini‐Mental State Exam and CDR Sum of Boxes) at ten years. Analyses were performed in the whole cohort, and in males and females independently.ResultHigher levels of baseline HDL‐cholesterol and lanosterol were associated with cognitive decline after ten years in the whole cohort. Decrease over time of 24S‐OHC was also associated with cognitive decline. In males, several cholesterol‐related sterols (cholestanol, lathosterol, lanosterol, 7α‐hydroxy‐cholesterol) and the phytosterol sitosterol were associated with cognitive decline. In females, only cholesterol and campestanol were associated with cognitive decline. The APOE genotype did not affect these associations.ConclusionIn this cohort of older people from the general population, plasma markers of cholesterol synthesis and metabolism and as well as phytosterols are associated with cognitive decline after ten years. These findings have potential relevance for sex‐specific risk assessment and prevention of cognitive decline in older people.
Modelling the impact of social isolation on the rate of cognitive decline of dementia patients
Authors: Myers James A C 
Published: December 2023

AbstractBackgroundThe current study looked to model the impact of social isolation (SI), using marital status as a proxy, on the rate of cognitive decline of dementia patients. It was hypothesised that patients with higher levels of SI (whose marital statuses reflected less socially connected living conditions) would exhibit steeper rates of cognitive decline over time than patients with lower levels of SI, and patients with higher levels of SI would have lower intercept cognitive scores compared to patients with lower levels of SI.MethodPatient demographic, diagnosis, cognitive assessment (Mini‐Mental State Examination [MMSE]/Montreal Cognitive Assessment [MoCA]) and marital status data were collated from electronic health records. Linear mixed‐effects models were used to explore the main effects and interaction effects of SI on the rate of cognitive decline of 4,137 patients from date of diagnosis to up to five years after (17,131 total observations).ResultComparisons for the MMSE and MoCA models showed the main effect models significantly outperformed null models testing the fixed effect of only diagnosis duration. The models revealed a similar rate of cognitive decline across all marital statuses. Excluding divorced patients, average intercept scores for less isolated marital statuses (married, civil‐partnership cohabiting) were higher than more isolated marital statuses (single, separated, widowed) for the MMSE models, but not the MoCA models. Interestingly, divorced patients had the highest average intercept scores in both the MMSE and MoCA models.ConclusionFuture research should look to develop the SI proxy using data from the COVID‐19 pandemic to explore the implications of isolation through enforced social restrictions on cognitive decline in dementia patients.
Adaptation and Modification of Digital Cognitive Assessments for Smartphone‐based and Unsupervised Conduct
Authors: Edgar Chris J. 
Published: December 2023

AbstractBackgroundRemote and decentralized approaches to clinical outcome assessments in clinical trials can reduce patient and trial burden, improve recruitment and retention, and lower barriers to trial participation. Remote assessment may be facilitated through smartphone‐based cognitive assessment, especially in Bring‐Your‐Own‐Device (BYOD) trials, and can also enable novel designs, for example, the use of high frequency ‘burst’ assessments. Application of such digital assessments in remote or unsupervised settings requires understanding of potential error from test administration and delivery platform (e.g., smartphones vs. computer).MethodA series of studies explored the modification of the well‐validated Cogstate Brief Battery (CBB) to include practice trials with dynamic feedback to support unsupervised cognitive assessment, and adaptations for smartphone delivery. Data were drawn from healthy populations in (1) the Healthy Brain Project, where middle‐aged adults (n = 1,594) completed unsupervised cognitive assessments on a computer, (2) a pilot study of young adults (n = 60) who completed both smartphone and computer administration, and (3) a large (n = 35,000) study of adults who completed unsupervised smartphone‐based cognitive assessments in a BYOD context.ResultData from middle‐aged adults enrolled in the Healthy Brain Project indicated that adaptation of the CBB for unsupervised computer‐based assessment had high levels of acceptability (98% complete data) and usability (95%), with data meeting criteria for low error rates and ease of understanding). In young adults, rates of test completion were high and comparable (>98%), and performance accuracy (d’s <0.2) was equivalent between smartphone and computer administration. Performance was systematically slower (d’s >0.4) on smartphone than computer. Smartphone usability was high (e.g., >85% found text and button size to be ‘just right’), but there was not a strong preference for smartphone versus computer (56% preferred smartphone) and different issues of fatigue, distraction, and use of keyboard input were raised for the platforms. Similar findings of outcome consistency across platform were observed in the large BYOD sample (N>35,000).ConclusionThese results indicate that smartphone assessment has high acceptability, good reliability, and that accuracy of performance is equivalent between smartphone and computer versions. The data also raise important issues for the successful adaptation and modification of cognitive tasks for smartphone administration.
Digital is the New Blood: Enabling the Present and the Future
Authors: Au Rhoda , Popp Zachary T , Low Spencer , Hwang Phillip H , De Anda‐Duran Ileana , Li Stephanie , Rahman Salman , Ding Huitong , Igwe Akwaugo , Karjadi Cody , Ang Ting Fang Alvin , Devine Sherral A. , Gurnani Ashita S , Mez Jesse B. , Farrer Lindsay A. , Sunderaraman Preeti , Lin Honghuang , Kolachalama Vijaya B. 
Published: December 2023

AbstractBackgroundDigital is the new blood, where collection, use, and storage of raw digital data streams enabled by technology‐embedded sensors are replacing analog methods. Analyses of digital data extend beyond current applications, analogous to previously stored blood currently be used for omics/biomarker research. Today digital technologies are used to measure Alzheimer’s disease (AD)‐related clinical symptoms (e.g., cognition, function, and behavior), but future possibilities remain to be determined. Importantly, digital data collection can go beyond current intermittent sampling by employing internet‐connected applications and devices that allow real‐time monitoring and accurate detection of changes, even within a widely heterogeneous spectrum.MethodBeginning in 2005, the Framingham Heart Study (FHS) began digitally recording participants’ spoken responses to neuropsychological (NP) test questions, and in 2011 extended to a digital pen to record written responses. The emergence of wearable devices and smartphone applications has led to an expanded use of digital technologies beyond recordings during NP assessments. The Boston University Alzheimer’s Disease Research Center (BU ADRC) leverages digital sensors in multiple internet‐connected devices that longitudinally collect digital data, in both in‐person and remote settings.ResultThe first publication involving FHS digital data was in 2016; the remaining (n> 17) have been from 2020‐current. Digital data measuring cognition, function and behavior are being collected through the BU ADRC, where results to date indicate nearly 100% and 75% uptake of active and passive engagement applications, respectively, and 95% uptake for wearable devices (n = 60). Longitudinal assessments include > 3 months for ∼50 participants; > 1 year for n∼21 participants.ConclusionOpportunities for improved trial outcome measurement are evident in the broad range of outcomes digital sensors capture beyond traditional research methodologies. Digital tools are being deployed for rapid screening for clinical trial inclusion, but more transformative opportunities are still to come. Replacing the sporadic and highly heterogeneous measures of cognition and related behaviors with more accurate measures that track treatment impact in real‐time at the individual level will shift the concept of clinically meaningful outcomes from group indicators to personalized ones. Digital is central to the realization of virtual clinical trial monitoring for precision treatment effects.