bluuebunny/crossref_metadata_2025_split huggingface dataset:
The (non)sense of diagnostic computer tools in memory clinics: An international survey assessing the views of clinicians, patients and caregivers
Authors: Van Gils Aniek M , Visser Leonie N.C. , Hendriksen Heleen M.A. , Georges Jean , Muller Majon , Bouwman Femke H. , van der Flier Wiesje M , Rhodius‐Meester Hanneke FM 
Published: December 2021

AbstractBackgroundComputer tools aid clinicians by combining test results and facilitating interpretation, in reaching decisions and communication, on both diagnosis and prognosis. Nevertheless, to date, such tools are hardly used in daily clinical practice. To optimally meet the needs of end‐users, as a prerequisite for further development and implementation of computer tools, we set out to identify barriers and facilitators for the use of computer tools in memory clinics according to clinicians. In addition, we aimed to synthesize the opinions of patients and caregivers about this topic.MethodsBetween July and October 2020, 109 European clinicians (45±10y, 49% F) completed an online survey on their views regarding the use of diagnostic and prognostic tools. Questions related to the willingness of using tools and factors that would hinder or stimulate the use. Furthermore, 50 European patients with SCD, MCI or dementia (73±8y, 34% F) and 46 caregivers (65±12y, 54% F) completed an alternative survey focused on their opinion.ResultsThe vast majority of clinicians reported a willingness to use diagnostic (80%) and prognostic (77%) computer tools. Increasing diagnostic accuracy was reported as the main factor to stimulate the use of a tool. In addition, clinicians indicated that tools should be easy to understand, time‐saving, and providing clear information on reliability and validity (Fig 1). Inadequate integration with electronic patient files and fear of losing important clinical information were most frequently indicated as barriers (Fig 1). Patients and caregivers were also positive about the use of computer tools by clinicians, both for diagnosis (71%) and prognosis (77%). They viewed computer tools as an addition to the current way of working, appropriate to modern times (Fig 2).ConclusionThis study shows that most end‐users are in favor of using computer tools in memory clinics, for diagnosis and prognosis. In order to stimulate implementation of computer tools, it is key to maximize the extracted information and to optimize integration with electronic patient files, while simultaneously provide clear information about reliability and validity. These insights pave the way for the further development of computer tools that meet the needs of end‐users and, consequently, successful implementation.
Alzheimer’s Disease (AD): Sarcopenia is associated with lower Mini‐Mental State Exam (MMSE) scores
Authors: Komatsu Caroline , Komatsu Ricardo S , Ariosa Rodrigo Hara , Sipioni Micheli 
Published: December 2021

AbstractBackgroundSarcopenia is highly prevalent in dementia, regardless of sarcopenia definition and irrespective of continent of study. According to the systematic review and meta‐analysis conducted by Chang et al. (2016), sarcopenia is independently associated with cognitive impairment.Methods195 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their sarcopenia levels assessed in consonance with the European Working Group on Sarcopenia in Older People (EWGSOP) and MMSE scores evaluated.Results55 out of 195 patients (28,20%) were diagnosed with sarcopenia (Low Mass Muscle ‐ LMM plus Low Muscle Strength – LMS or Low Physical Performance – LPP). From the sarcopenia group 4 patients (7,28%) presented severe cognitive impairment (MMSE < 10), 25 patients (45,45%) presented moderate cognitive impairment (MMSE = 10 – 20) and 26 patients (47,27%) presented mild cognitive impairment (MMSE > 20). From the non‐sarcopenia group 11 patients (7,86%) presented severe cognitive impairment, 45 patients (32,14%) presented moderate cognitive impairment and 84 patients (60%) presented mild cognitive impairment. Both groups, sarcopenia and non‐ sarcopenia, had on average the same educational level: 2,93 and 3,66 years respectively.ConclusionIn this sample of patients with AD, sarcopenia is associated with lower MMSE scores when compared to non‐sarcopenia.
The first female engineer at General Motor’s descent into Alzheimer’s with sundowners: A daughter’s scholarly research and case study as caregiver
Authors: Keely Amy J 
Published: December 2021

AbstractBackgroundAlzheimer’s with Sundowners continues to be one of the greatest challenges between the patient and caregiver. Sundowners familial caregivers are often reluctant to place their loved one’s into facilities in part due to the stigma around the aggressive behaviors and also concerns about the care their loved one will receive.MethodsIn a comparative analysis between my grandmother who had Alzheimer’s and my mother with Alzheimer’s with Sundowners, there are key differences supporting the behavioral nature of Sundowners from my mother's diagnosis in 2014. Investigations into the emerging research around dementia lucidity, is confirmed by levels of ‘awareness’ my mother had until her death in February 2020. Research captures levels of caregiver burnout and the types of tools for long‐term facilities to demarcate between ‘traditional’ Alzheimer’s and Sundowners. This behavioral research includes videos, caregiver case studies, and cognitive decline shown through artwork, that will provide evidence that dementia lucidity causes Sundowners behavior issues as patients are aware, scared, and terrified of an increasingly confusing world.ResultsBehaviorally “difficult” patients – like my mother – continue to be treated with ‘chemical restraints’ offered by harsh off label anti‐psychotic drugs with FDA black box warnings that are burning through their remaining delicate synapses. Training is required to provide Sundowner patients with a higher level of engagement. Treatment at earlier stages should include testing for melatonin/serotonin levels for treatment, different applications of music/light therapy, Art therapy, CBD/THC treatment, and behavioral redirects to keep Sundowners patients calm.ConclusionQuarterly online self‐directed training with assessment scoring and gamification will help embed behavioral redirects techniques (especially during the first six months at a facility) and support distressed families. Better levels of engagement results in calmer patients so they can have greater dignity as they go through the final throws of brain death. ‘I need to go home”, isn’t a physical place where they want to go, but a cry for help to find a mental place of comfort ‐ just as a child reaches for a favorite blanket – and we owe them that place of peace.
Sleep characteristics associated with mild cognitive impairment among rural‐dwelling older adults: The MIND‐China study
Authors: Liu Rui , Tang Shi , Ren Yifei , Wang Yongxiang , Cong Lin , Du Yifeng , Qiu Chengxuan 
Published: December 2021

AbstractBackgroundSleep characteristics associated with mild cognitive impairment (MCI) and its subtypes are poorly defined in old age. We sought to characterize the sleep disturbances associated with MCI, subtypes of MCI, and specific cognitive domains among rural‐dwelling older adults in China.MethodThis population‐based cross‐sectional study included 4469 participants (age ≥65 years, 56.4% women) who were free of dementia and living in the rural communities in Yanggu County, Shandong. We collected data through interviews, clinical examinations, neuropsychological testing, and laboratory tests. We used the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale to evaluate various sleep parameters. Specific domain of cognitive function were assessed with the Auditory Verbal Learning Test (immediate recall, long‐delayed free recall, and long‐delayed recognition) for memory, the Semantic Verbal Fluency Test for language, the Digit Span Test for attention, and the Trail Making Test A & B for executive function. MCI was diagnosed according to the Petersen’s criteria. Data were analysed using logistic and general linear regression models.ResultMCI was diagnosed in 1204 participants (940 with amnestic MCI [aMCI], 264 with nonamnestic MCI [naMCI]). The multivariable‐adjusted odds ratio (OR) of MCI was 1.45 (95% CI 1.14‐1.83) for sleep duration ≤4 hours/night (vs. >6‐8 hours/night), 1.39 (1.12‐1.72) for sleep duration >8 hours/night, 1.23 (1.06‐1.43) for poor sleep quality, 1.46 (1.25‐1.70) for low sleep efficiency, 1.29 (1.10‐1.50) for prolonged sleep latency, and 1.49 (1.17‐1.88) for excessive daytime sleepiness (EDS). These sleep characteristics were significantly associated with aMCI (multi‐adjusted OR range: 1.27‐1.46; p<0.05). EDS was significantly associated with naMCI (multi‐adjusted OR 1.56 [1.04‐2.33]). In addition, short and long sleep duration, poor sleep quality, low sleep efficiency, prolonged sleep latency, and EDS were associated with worse memory function. Long sleep duration, low sleep efficiency, and EDS were associated with worse language function. Low sleep efficiency and EDS were associated with worse attention function. However, none of the examined sleep parameters was significantly associated with executive function.ConclusionShort and long sleep duration, poor sleep quality, low sleep efficiency, prolonged sleep latency, and EDS were associated with an elevated likelihood of MCI, especially aMCI and poor memory function.
Novel use of tau imaging to enrich for pathological homogeneity within the PERISCOPE‐ALZ study of zagotenemab
Authors: Munsie Leanne M , Lo Albert C. , Fleisher Adam S , Andersen Scott W. , Shcherbinin Sergey , Sims John R. , Brys Mirek , Mintun Mark A 
Published: December 2021

AbstractBackgroundZagotenemab (LY3303560), a humanized monoclonal antibody targeting extracellular aggregated tau, is currently in development as a potential disease modifying treatment for early symptomatic Alzheimer’s disease (AD). The PERISCOPE‐ALZ study (Phase 2, NCT03518073) of zagotenemab implements tau PET for classifying AD pathological stage based on the NIA‐AA guidelines (Jack CR, Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535‐62) and serves as a key eligibility criterion. Here we summarize the study’s screening and baseline characteristics.MethodScreening procedures were performed at 60 sites in the United States, Canada, and Japan. Key eligibility criteria include age of 60‐85 years, Mini‐Mental State Exam (MMSE) score of 20‐28, and pre‐defined baseline tau load as assessed by flortaucipir F18 PET. This eligibility strategy was intended to exclude participants with minimal tau burden whose pathology may not be consistent with AD in absence of amyloid pathology confirmation and who are expected to have slower clinical progression. Participants with high tau levels, hypothesized to be less likely to respond to therapy, were also excluded.ResultThe most common reasons for screen failure were out of range baseline tau levels and cognitive screener score. Of screened participants who underwent a flortaucipir scan, 58% did not meet scan eligibility criteria. Seventy‐nine percent of the flortaucipir scans not meeting eligibility criteria were below pre‐defined tau levels required for inclusion. A higher proportion of females than males who were ineligible based on the tau scan harbored too high of tau levels for eligibility (27% v. 14%, chi‐square p=0.0004). The enrolled cohort had an average age at baseline of 75 years and 53% were female. Average MMSE score at baseline of the enrolled cohort was 23.7.ConclusionPERISCOPE‐ALZ successfully implemented flortaucipir PET imaging as the key inclusion criterion to enroll a pathological homogeneous cohort based on level of tau accumulation. As tau‐targeted therapies for AD advance into clinical research, staged tau pathology as eligibility criterion may be useful in phase 2 proof‐of‐concept trials to test disease modifying therapies. Topline trial results are anticipated in late 2021.
Hospital readmissions following infections in dementia: A nationwide and registry‐based cohort study
Authors: Janbek Janet , Frimodt‐Møller Niels , Laursen Thomas Munk , Waldemar Gunhild 
Published: December 2021

AbstractBackgroundUnplanned acute hospital readmissions put persons with dementia at risk for adverse health outcomes. It is crucial to identify avenues for effective interventions to decrease or prevent unnecessary readmissions, especially in particularly vulnerable patient groups such as those living with dementia and particularly for common and potentially preventable reasons for hospitalization such as infections. Relatively little is known about hospitalization trajectories for people with dementia who get admitted to a hospital with an infection, and surprisingly little is described and documented in literature. We aimed to investigate readmission risks (with dementia and without); identify types of infections behind risks; and highlight reasons for readmissions.MethodRegistry‐based cohort of elderly patients with acute inpatient hospital admissions for infections in Denmark included from January 1, 2000 or age 65 years. Primary outcomes: 7‐day readmissions (Risk Ratios [RR]: Risk following index admissions with dementia relative to without); risks by infection site, and reasons for readmission (secondary: 30‐ and 90‐day readmission). Competing risk of death was estimated.Result789,732 index admissions (421,133 people) were included and resulted in 55,303 readmissions in 7 days (10% followed admissions with dementia) and 78,732 deaths (14% followed admissions with dementia). Readmission and mortality RRs were higher following index admissions for infections than for other causes. Seven‐day readmission RR was increased in all ages and highest in the youngest (Women RR 1.37, 95% confidence interval [CI] 1.22‐1.53; Men RR 1.23, 95% CI: 1.12‐1.35). RRs reduced with increasing age and longer follow‐up (where some were insignificant or decreased). Readmission risks were notably higher following admissions with dementia in the youngest ages in all infection sites, and reasons for readmission varied by infection site and were most commonly due to infection (either linked/unresolved or other infection) and dehydration.ConclusionFindings highlight need for improvements in preventing and treating infections in people with dementia, and in ensuring successful transition from the hospital to the community that includes individualized care and close follow‐up by caregivers and skilled health personnel. In‐depth investigations of determinants related to readmission risk are needed, to highlight important avenues for interventions to decrease or prevent potentially avoidable readmissions.
More than a memory test: A new metric linking blocks, numbers, and words
Authors: Melin Jeanette , Cano Stefan , Flöel Agnes , Göschel Laura , Pendrill Leslie ,   EMPIR NeuroMET and NeuroMET2 consortiums
Published: December 2021

AbstractBackgroundThe extent to which existing legacy memory tests are accurate and sensitive in detecting early cognitive decline is questionable. This reflects the wider picture in neurodegenerative conditions where clinical rating scales have not been developed for early‐stage disease. Item banks delivered through computer adaptive tests can help. But, in order to be fit‐for‐purpose, this approach requires a metrological framework with recourse to units, traceability, and interoperability. Here we describe the initial research to build such an item bank, based on legacy tests.MethodMemory tests (i.e., Corsi Block Test [CBT], Digit Span Test [DST], Rey’s Auditory Verbal Learning Test [RAVLT] and Word Learning List [WLL]) data were collected in the European EMPIR NeuroMET and the SMART cohorts recruited in Charité Hospital (Healthy control n 86; Subjective Cognitive Decline n 99; Mild Cognitive Impairment n 37; and Alzheimer’s Disease n 45). In order to align with metrological requirements, Rasch measurement theory in conjunction with construct specification equations were chosen to analyse the data.ResultBased on the combined dataset, when analyzed on their own, the data from the CBT, DST, RAVLT and WLL revealed skewness, gaps, and large measurement uncertainties. The addition of items from each of the tests into a bank improved these psychometric issues, improving reliability from a minimum of 0.65 to 0.85. The metrological legitimization of the ‘NeuroMET Memory Metric’ (formed from the combination of items) was confirmed through construct specification equations, which provided a Pearson correlation coefficient for empirical values vs. predicted (zR) values of up to 0.98 for task difficulty.ConclusionOur early promising findings provide a strong foundation for a metric of memory ability, which can be used as the basis for computer adaptive testing, better targeted measurement, and more accurate discrimination of early cognitive decline. Establishing units can also provide for the potential of developing crosswalks between a wider range of memory test items. Further work includes further longitudinal data collection to confirm item estimates, development of a digital platform, and a quality assurance program to establish traceability, and interoperability.
Artificial Intelligence empowered recruitment for clinical trials
Authors: Linz Nicklas , ter Huurne Daphne BG , Langel Kai , Ramakers Inez HGB , König Alexandra ,   DeepSpA
Published: December 2021

AbstractBackgroundRecruitment of clinical drug trials for Alzheimer's disease (AD) is a lengthy process with an ultimately high screening failure rate, as current research focuses on prodromal stages. We evaluate the option of pre‐screening potential participants for AD trials via an automated phone‐based assessment using speech analysis.Method140 participants were recruited at the memory clinic in Maastricht as part of the MUMC+ study (SCI, MCI, ADD). They underwent a in‐person baseline assessment (0M) at the clinic. Cognitive assessments were performed and speech was recorded during each assessment using the Delta platform. For the next assessments (6M), participants were contacted via telephone by a trained research nurse. Cognitive assessments were performed on the phone and speech was recorded during each assessment. Speech from each assessment point was analysed automatically to extract relevant features. Machine learning models to predict disease status, Clinical Dementia Rating Scale (CDR) scores, and Mini‐Mental‐Status‐Examination scores were trained and evaluated on the data.ResultModels based on speech features extracted from the phone assessment were able to predict disease status with an AUC of 0.93±0.06, CDR score with a Mean Absolute Error (MAE) of 1.9±0.8, and MMSE score with an MAE of 2.3±1.1. Adding longitudinal data from baseline assessments increased accuracy across all models.ConclusionAutomated pre‐screening through speech analysis could be an effective tool to increase the efficiency and effectiveness of recruitment for AD drug trials.
Motor proficiency composite scores as a novel biomarker for Alzheimer's disease
Authors: Koppelmans Vincent , Ruitenberg Marit F.L. , Van der Geest Jos , Duff Kevin M. 
Published: December 2021

AbstractBackgroundMild cognitive impairment (MCI) and Alzheimer's disease (AD) are associated with various motor impairments in ambulatory and manual measures that involve speed, force, and precision. Prior studies suggest that such motor impairments are an early disease marker and predict AD progression. A composite motor score that combines motor measures spreading the breadth of motor domains could be a stronger predictor than individual motor measures. Here, we evaluate associations of motor composite scores with existing AD biomarkers in a combined group of individuals with MCI and AD, and cognitively normal individuals.MethodAll participants, who were classified by ADNI‐2 criteria, completed the following motor measures: 1) grip strength using a hand‐dynamometer; 2) general motor reaction time assessed as the time between the visualization of stimuli on a computer screen and pressing a button; 3) psychomotor speed using the Trail Making Test Part A; 4) unimanual and bimanual finger tapping speed using a keyboard; and 5) drawing speed and accuracy using the computerized Archimedes spiral tracing test. Motor composite scores were defined as the sum of the z‐transformed raw measures. Additionally, participants underwent APOE genotyping to determine the presence of e4 alleles, amyloid PET imaging to quantify amyloid deposition, and structural MRI scanning to obtain hippocampal volume. Correlational analysis was used to test the association between motor composite score and AD biomarkers.ResultTo date, 5 cognitively normal, 7 MCI, and 9 AD subjects completed all assessments. Motor composite scores were significantly and strongly associated with AD biomarker scores (p<.05 and Cohen's d>.8 for all outcomes; see Figure 1). Individuals with more APOE e4 alleles had worse motor composite scores (Rho=‐0.43). Higher amyloid burden was related to worse motor composite scores (r=‐0.51). Larger volume of the left hippocampus correlated with better motor composite scores (r=0.51).ConclusionMotor proficiency, as reflected in composite scores, is strongly associated with established markers of AD. Ongoing work focuses on expanding our sample size to allow for statistical correction for potential confounders such as age, stratify the sample to study potential sex differences, and compare motor scores to neuropsychological test scores collected in this sample.
Association of antiherpetic medication with incident dementia in Denmark, Wales, Germany and Scotland
Authors: Schnier Christian , Janbek Janet , Williams Linda , Wilkinson Tim , Laursen Thomas Munk , Waldemar Gunhild , Richter Hartmut , Kostev Karel , Lathe Richard , Haas Juergen 
Published: December 2021

AbstractBackgroundSeveral epidemiological studies from Taiwan, all using the same data resource, found significant associations between herpes virus infection, antiherpetic medication and dementia. We conducted a multicenter observational cohort study using health registry data from Wales, Germany, Scotland, and Denmark to investigate potential associations between antiherpetic medication and incident dementia, and also to comprehensively investigate such associations broken down according to medication type and dose, type of herpes virus, and dementia subtype.Method2.5 million people aged 65 and older were followed up using routinely collected linked electronic health records in four separate national observational cohort studies. Exposure and outcome were classified using coded data from prescriptions and from primary and secondary care. Data were analyzed using survival analysis with time‐dependent covariates. Confounders were age, year, sex, socioeconomic status, and comorbidities.ResultResults were heterogenous across cohorts (Figure 1), with a tendency for decreased dementia risk in people exposed to antiherpetic medication (Wales: HR 0.91, 95% CI 0.86 to 0.97; Denmark: HR 0.91 (0.89 to 0.93); Germany: HR 1.08 (0.98 to 1.20); Scotland: HR 0.98 (0.64 to 1.49). Associations were not affected by number of treatments, herpes diagnosis, type of dementia, or specific type of medication. People diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk in the German cohort (HR: 1.18; 1.09 to 1.28) but not in the Welsh cohort (HR: 0.95; 0.88 to 1.02).ConclusionResults from the four large cohorts allow us to exclude any major association of short‐term exposure to antiherpetic medication with dementia. Because neither type of dementia nor type of herpes infection modified the association, the small but significant decrease in dementia incidence with antiherpetic administration mayeflect unmeasured confounding and misclassification.