bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability and participant acceptance of remotely administered RBANS in an MCI and Alzheimer’s disease cohort
Authors: Hunter Matthew B , Saunders Stina , Russ Tom C , Ritchie Craig W. , Muñiz‐Terrera Graciela 
Published: December 2021

AbstractBackgroundIn light of the COVID‐19 pandemic, it is increasingly likely that researchers will adopt home‐based remote administration of cognitive tests for the continuation of clinical studies. Yet, there are limited data on the reliability of remotely administered cognitive assessments compared to in‐person. Specifically, cross‐modal reliability of the RBANS has not been assessed under naturalistic home conditions in older persons with MCI and Alzheimer’s Dementia (MCI/AD). As this population has difficulties with communication and technology, an evaluation of participant acceptability of remote administration is warranted to gauge future engagement. The aim of this study was to provide cross‐modal test‐retest reliability estimates for the RBANS in a cohort of people with MCI/AD, obtain participant attitudes toward remote assessment, and explore the relationship between attitudes and test scores.MethodMCI/AD participants were recruited from NHS Scotland clinical services onto an ongoing community‐based longitudinal cohort study. Participants received multiple at‐home RBANS assessments, followed by an at‐home remote assessment ‐ due to local changes in travel restrictions following the COVID‐19 pandemic. Remote administration was conducted via telephone or videoconference, depending on participant preference. Following adjustment for multiple in‐person data points, intraclass correlations, means, and variance tests were selected to statistically analyse cross modal reliability. A locally developed 13 item Likert scale acceptability questionnaire was administered to assess call quality, and participant attitudes toward remote assessment.ResultAt time of submission, N=46 MCI/AD participants completed both in‐person and remote (N=29 videoconference, N=17 telephone) RBANS assessments. Data collection is ongoing and up‐to‐date findings would be presented at the AAIC. Test‐retest reliability data will be presented at the item and index level for telephone and videoconference administrations, providing a comprehensive reliability analysis. Questionnaire data will be presented quantitatively and will portray attitudes toward remote assessment in comparison to in‐person assessment, controlling for call quality and test performance.ConclusionThis study will provide ecologically valid RBANS reliability data in an MCI/AD population. The results of the acceptability questionnaire will provide evidence for individuals’ willingness to engage in future remote assessment.
Regression based machine learning model for dementia diagnosis in a community setting
Authors: Salem Fatima Abu , Chaaya Monique , Ghannam Hiyam , Al Feel Roaa E , El Asmar Khalil 
Published: December 2021

AbstractBackgroundAs the world’s population ages, the prevalence of cognitive decline, dementia and Alzheimer’s disease is on the increasing trend. From a public health perspective and the absence of a cure, the early identification of individuals at risk of dementia becomes of paramount importance for proper early prevention. We developed a ML application for dementia diagnosis that is based on the 10/66 one stage dementia diagnostic algorithm.MethodTraining and testing data belonged to three community based surveys conducted in Lebanon as part of a larger dementia cohort study. Our training sample was 802, our testing sample 200, with the dataset showing imbalance (20% positive, 80% negative). In our supervised approach, we explore techniques for imbalanced learning beginning with artificially oversampling the minority class and undersampling the majority class, in order to decrease the bias of any model to be trained on the dataset. Additionally, we incorporate cost‐sensitive techniques to over‐penalise the models when misclassifying an instance in the minority class. We explore both models that produce a probability that a person has dementia, as well as models that produce a crisp class label (dementia or not).ResultThe best model hyperparameters including the cost to be incorporated and the percentage of oversampling/undersampling are tuned via three times repeated, 10‐fold stratified cross validation. The balanced random forest was considered as our most robust probabilistic model ‐ using only 20 features/variables‐ with a F2 score=0.82 and G‐Mean= 0.88 and ROC AUC=0.88. The Calibrated Weighted SVM for the same number of features was our best classification model with F2‐score=0.74 and a ROC AUC=0.80ConclusionCompared to the regular 10/66 one stage dementia diagnostic algorithm, our proposed models show very promising results and high level of accuracy by using only a 20 variables predictive model. With additional data, such models can gain in accuracy, precision and efficiency. Machine learning based models would serve as a valuable community dementia screening and diagnostic tools.
Does targeted medication therapy management increase cognitive reserve? Results from the INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression (INCREASE) study
Authors: Moga Daniela C , Abner Erin L , Schmitt Frederick A , Eckmann Lynne , Huffmyer Mark , Martinez Ashley I , Beech Brooke F , George Rosmy , Khouli Riham H El , Ali Doaa , Jicha Gregory A 
Published: December 2021

AbstractBackgroundThe INCREASE study is based on the hypothesis that targeted reductions in inappropriate medication use will bolster cognitive reserve (CR) in individuals at risk for Alzheimer’s Disease (AD), delaying the onset of clinical symptoms, and reducing the prevalence and duration of symptomatic disease.MethodWe conducted a 12‐month, randomized controlled trial to: (1) evaluate the impact of a medication therapy management (MTM) intervention in reducing unnecessary and inappropriate medication use in community‐dwelling, non‐demented older adults, (2) determine the impact of preclinical amyloid burden on CR deficits and decline to evaluate efficacy of delaying symptomatic disease progression in preclinical AD (pAD). Primary outcome measures included pre‐ to post‐intervention measures of: (1) medication use ( Medication Appropriateness Index, MAI); 2) CR Change Score (CRCS) defined as the difference in the scopolamine‐challenged vs unchallenged neurocognitive scores (Trail Making Tests A and B; California Verbal Learning Test, CVLT) . For the second aim, we used baseline determination of total brain relative standardized uptake values for amyloid β‐ positron emission tomography to examine the relative impact of pAD pathology on CRCS at baseline and over time in the placebo group, as well as the interplay of pAD pathology with inappropriate medication use at baseline and optimization of medication use after one year.ResultWe randomized 90 community‐dwelling participants (N=104 screened for eligibility). Mean (SD) age at enrollment was 73.9 (6.0), with N=57 (63%) female, and N=10 (10%) non‐white participants. At baseline, participants reported using a mean (SD) of 12.72 (4.87) medications, with 2.37 (1.29) potentially inappropriate (Beers 2015 criteria). In preliminary analyses, participants with pAD (N=29) had lower baseline CR for tests of executive function (mean (SD) change score ‐0.17 (1.37) and ‐0.13 (1.10) [p=0.90] for pAD and non‐pAD respectively) and total learning (‐0.85 (0.84) and ‐0.29 (0.83) [p=0.01]). At the time of abstract submission, we anticipate that data collection will be finalized by March 31, 2021 and we are planning to present main study results during AAIC 2021.ConclusionThe results of the INCREASE study will provide insights on the impact of optimizing medication use to bolster CR, as well as the interaction with preclinical amyloid burden.
Brain health actions: Evidence from the electronic Person‐Specific Outcome Measure (ePSOM) development programme
Authors: Ritchie Craig W. , Saunders Stina , Sheehan Shane , Luz Saturnino , Muñiz‐Terrera Graciela 
Published: December 2021

AbstractBackgroundAs Alzheimer’s disease (AD) clinical trials move to an earlier phase in the neurodegenerative disease process, any outcome measures used to assess an intervention’s efficacy would need to be appropriate for the earlier pre‐clinical or prodromal study population. Evidence suggests that 40% of dementia cases could be prevented by targeting modifiable risk factors. Our study explores attitudes towards looking after one’s brain health and by proxy, actions individuals take to prevent dementia.MethodAs part of the electronic Person Specific Outcome Measure (ePSOM) online study focusing on what outcomes matter to individuals, we collected data on specific actions individuals take to maintain their brain health. The question on brain health offered pre‐defined answers as well as an option for free text answers. Here, we report both the results from the pre‐defined answers as well as the analysis of the large free text answers data set. We used Natural Language Processing (NLP) techniques based on pretrained GloVe vectors to cluster the free text responses. The survey received ethical approval and ran August – November 2019 (UK).Result5808 people completed the ePSOM survey. Most were female (76.9%), married (63.4%) and living in an urban area (61.8%). The mean age in women was 57.35 (SD=13.8) and 62.88 (SD=13.08) in men. The most common activities undertaken to maintain brain health from the pre‐defined answers were “trying to keep brain active” (86.6%) followed by “trying to keep physically active” (70.8%). However, the NLP analysis of the 621 individual free text answers revealed 45 clusters which were not included in the pre‐defined categories. Some of the largest clusters were around mindfulness; learning new words/languages and preventing mood swings. These results will be presented in further detail by key demographic groups.ConclusionThe ePSOM study has generated evidence on what activities individuals purposefully undertake to maintain brain health. The results of our study provide evidence for public health campaigns on which modifiable risk factors are more or less commonly known to prevent dementia.
Correlation of a mobile‐based cognitive test app with traditional neuropsychological tests in a community‐based cohort
Authors: Au Rhoda , Devine Sherral , Young Katie , McManus Chelsea , Lin Honghuang 
Published: December 2021

AbstractBackgroundOver the past decade, a number of digital health devices and mobile apps have been developed to monitor cognitive health. These digital technologies provide the potential as a convenient and cost‐effective solution for cognitive health. However, many of them were tested only in a controlled environment with limited samples, whereas their validity for longitudinal cognitive health monitoring is largely unknown.MethodThe study included participants from the Framingham Heart Study (FHS) who previously completed traditional neuropsychological (NP) tests in the FHS research center. Participants were asked to complete additional cognitive tests using Defense Automated Neurobehavioral Assessment (DANA), which is the first FDA cleared mobile app with 9 different cognitive tests, including Code Substitution, Go No Go, Insomnia Severity Index, Match to Sample, Memory Search, Patient Health Questionnaire, Procedural Reaction Time, Simple Reaction Time, and Spatial Processing. Participants were asked to complete at least three tests at the baseline, and every three months. The correlation between DANA tests and 18 traditional NP tests were assessed by the Pearson correlation coefficient test.ResultOne hundred and twenty one participants were included in the current study (mean age 71±8, 64.5% women). These participants completed an average of 2.9 repetitive tests during a median of seven month follow‐up period. All DANA tests were correlated with at least one NP test with nominal significance (P<0.05). Three NP tests were correlated with Procedural Reaction Time and two NP tests were correlated with Code Substitution after Bonferroni correction for multiple testing (P<3.1x10‐4). The most significant correlation was observed between Procedural Reaction Time from DANA and the Trails B test that was conducted in the FHS research center, with correlation coefficient of 0.44 (P=6.8x10‐7). The correlation remained significant during follow‐up DANA tests (correlation coefficient=0.44, 0.34, and 0.41 for the 2nd, 3rd and 4th DANA exams, respectively).ConclusionOur study suggests that traditional NP tests were highly correlated with some DANA tests, which might be used as an alternative approach for habitual cognitive health monitoring in a person’s natural environment.
Transgender adults report greater cognitive and related functional challenges: Findings from the 2015‐2019 Behavioral Risk Factor Surveillance System
Authors: Cicero Ethan , Flatt Jason D , Wharton Whitney 
Published: December 2021

AbstractBackgroundThere is limited research investigating cognitive impairment and Alzheimer’s disease and related dementia (ADRD) among transgender adults. Transgender adults experience more health disparities and psychosocial stressors, including high rates of depression, discrimination, and chronic health conditions, compared to cisgender adults. The inequities endured by transgender adults are linked to an increased risk of cognitive impairment in other marginalized groups. Subjective cognitive decline (SCD), a self‐reported experience of worsening memory or thinking, is one of the first clinical manifestations of ADRD.MethodCombined data from the 2015‐2019 Behavioral Risk Factor Surveillance System (BRFSS) surveys, representing 33 states that used the SCD and gender identity modules, were analyzed to examine SCD and associated functional limitations among transgender and cisgender adults. BRFSS, an annual cross‐sectional telephone survey, collects data on the health and health behaviors of non‐institutionalized adults aged >18 living in the US. The sample included 386,529 adults aged >45 (transgender, N=1,302; cisgender, N=385,227). Logistic regression methods were used to determine the SCD and SCD‐associated functional limitations prevalences and test for differences in prevalence, demographic characteristics, and chronic health conditions among transgender and cisgender adults.ResultTransgender adults were 1.73x more likely to report SCD (17.06% vs 10.64%, 95% CL: 1.44‐2.08, P<0.001) and 2.30x more likely to report SCD‐related functional limitations (64.71% vs 44.37%, 95% CL: 1.62‐3.27, P=<0.0001) when compared to cisgender adults. Among those reporting SCD, transgender adults were younger (mean 61.89 vs 65.15 years, P=0.0005), more likely to be a racial/ethnic minority (37.31% vs 19.53%, P<0.0001), a high school graduate or less (59.56% vs 43.42%, P=0.0003), uninsured (17.04% vs 5.53%, P=0.0007), have a depressive disorder (58.82% vs 45.74%, P=0.0028).ConclusionAdditional studies are needed to further understand correlates and modifiable risk factors of cognitive impairment among transgender adults. This understanding is necessary for identifying and targeting of preventive intervention strategies for transgender adults who are at higher risk of cognitive impairment and ADRD, developing culturally relevant screenings, and shape policies to improve the health and well‐being of transgender adults.
Characteristics of chemokines and pro‐inflammatory cytokines in elderly with major depressive disorder
Authors: Nie Jing , Li Xia , Qiu Qi 
Published: December 2021

AbstractBackgroundResearch evidence has shown that late life depression (LLD) and amnestic mild cognitive impairment (aMCI) are both related to Alzheimer's disease (AD) and usually accompanied by inflammatory dysregulation, but few studies have compared the levels of chemokines and cytokines between these two disorders.MethodSixty‐nine study subjects were age‐ and gender‐matched outpatients with LLD or aMCI without dementia (based on DSM‐IV criteria) and normal controls (NC) in community. All individuals were administered Chinese versions of MoCA, Chinese version of neuropsychological test battery and Geriatric Depression Scale. Chemokines and pro‐inflammatory cytokines, including C‐X‐C chemokine ligand(CXCL5, CXCL6, CXCL8, CXCL9, CXCL11,CXCL16),C‐C chemokine ligand (CCL1,CCL7,CCL3, CCL8,CCL19,CCL20,CCL24,CCL11,CCL23,CCL27, CCL2, CCL13, CCL15, CCL17, CCL25), high sensitive C‐reactive protein (hsCRP), Interleukin 1‐beta (IL‐1β), macrophage inflammatory protein (MIP)‐2, Interferon‐γ‐inducing factor(IFN‐γ), vascular cell adhesion molecule‐1(VCAM‐1), interleukin‐2(IL‐2),interleukin‐4(IL‐4), tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6) were assessed in all subjects by Luminex assays.ResultElderly with major depressive disorder had less education, lower rate of having habits in taking regular exercise or drinking tea and even lower scores on cognitive tests than aMCI patients and healthy controls. LLD group showed higher level of IL‐6( P < 0.05 ) than the control or mild cognitive impairment subjects. However, They exhibited a significantly lower levels of CXCL5,CXCL6,CXCL16, and CCL5 (all p < 0.05) than the NC groups. Furthermore, The results also showed that LLD group had lower levels of CCL2,CCL17,CCL15,CXCL11 and CCL13 than the aMCI group. The multiple regression analysis showed that CCL25,CXCL6 was significantly related to cognitive scores in female.ConclusionWe are the first to report that LLD show different characteristics in inflammatory dysfunction from amnestic mild cognitive impairment patients and normal controls. Low levels of CCL2, CCL5,CCL13, CCL15,CCL17, CXCL5,CXCL6,CXCL11and CXCL16 were found in LLD than in aMCI. These results may suggest a quite different inflammatory dysregulation in LLD from aMCI though elderly with depression also show deficits in cognition. Future longitudinal studies should further explore the heterogeneity of LLD and whether these cytokines could be early markers to predict dementia.
Accelerated long‐term forgetting: Prognostic utility in familial Alzheimer’s disease
Authors: Alston Duncan , O'Connor Antoinette , Weston Philip SJ , Lu Kirsty , Pavisic Ivanna M , Rice Helen , Street Rebecca E , Bowman Erinna , Crutch Sebastian J , Fox Nick C 
Published: December 2021

AbstractBackgroundIn Alzheimer’s disease (AD), temporal lobe pathology begins years before onset of clinical symptoms1. Early detection of temporal lobe dysfunction would be valuable for trials. Accelerated long‐term forgetting (ALF) – failure to recall learnt material when the interval of testing is extended to days as opposed to the traditional interval of minutes – has been shown to be a sensitive measure of early cognitive change in AD. However, it is not clear if ALF can predict future progression. Here we investigate the prognostic utility of ALF by assessing whether baseline performance is associated with subsequent cognitive and clinical decline.MethodThirty‐five at‐risk participants were recruited from UCL’s Longitudinal Cohort Study of Familial Alzheimer’s Disease (FAD). At baseline ALF was assessed by comparing recall performance at 7 days to performance after a 30‐minute interval. Visual (figure) and verbal (list and story) measures were used. Annual follow‐up visits included a detailed neuropsychological battery, mini‐mental state examination, Clinical Dementia Rating scale (CDR), measures of anxiety and depression and subjective memory decline. We tested for an association between baseline performance in ALF and rates of change in cognitive and clinical measures.ResultsAt baseline, mean time to estimated symptom onset (based on parental age at onset) for mutation carriers was 7.2 years (SD 4.5 years). Four mutation carriers became symptomatic (CDR>0); baseline performance in these cases was in the 5th‐23rd percentiles for verbal measures of ALF. We will present the value of accelerated long‐term forgetting in predicting cognitive decline in this cohort.ConclusionALF is a feature of presymptomatic AD with potential utility in stratification and prognostication. References: 1. Bateman, R.J. et al. N. Engl. J. Med.
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Multifunctional edaravone‐N‐benzyl pyridinium derivatives: AChE inhibition kinetics, in vitro neuroprotective activities and BBB permeability studies
Authors: Zondagh Luke Shand , Joubert Jacques , Omoruyi Sylvester , Mentor Shireen , Malan Sarel F , Ekpo Okobi E , Fisher David 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that is mainly prevalent in the older population. Approximately fifty million people are diagnosed with dementia, with AD accounting for 60–70% of these cases. Amyloid beta (Aβ) is considered a pathological hallmark of AD. The shorter Aβ 25 – 35 peptide fragments, formed from the amyloidogenic Aβ 1–40 peptide, plays a crucial role in the peptide’s neurotoxic activity (Pike et al., 2002). Acetylcholinesterase (AChE) as well as oxidative stress have shown to trigger Aβ formation and aggregation (Belluti et al., 2011; Cheignon et al., 2018). Previously, we synthesized multifunctional edaravone‐N‐benzyl pyridinium compounds that exhibited potent AChE inhibition and antioxidant activity as well as predicted to cross the blood‐brain barrier (BBB) using in silico models (Zondagh et al., 2020).MethodSelected compounds were chosen to further investigate their AChE inhibitory kinetics, Aβ 25 – 35 and MPP+ attenuating ability, cytotoxicity and in vitro BBB permeability. The AChE inhibitory kinetics were determined using a modified Ellman’s method. The data was analyzed, and a double‐reciprocal Lineweaver‐Burk plot was drawn. Mode of inhibition was determined from the Lineweaver‐Burk plot. The compounds in vitro Aβ 25 – 35 and MPP+ attenuating activity and cytotoxicity at concentrations of 10 – 100 µM was assessed on the SH‐SY5Y cell line. The in vitro BBB permeability of the compounds were assessed on the b.End5 cell line.ResultAll of the compounds exhibited mixed non‐competitive – uncompetitive mode of AChE inhibition which correlate with previous molecular docking studies. Four of the five compounds exhibited no cytotoxic effects to the SH‐SY5Y cell line, with some exhibiting proliferating effects. Compound 5a, 5e and 5j caused greater cell proliferation compared to the control at 10 μM. Most of the compounds exhibited significant activity at attenuating MPP+ and Aβ 25 – 35. Compounds 5a, 5b and 5e exhibited the most promising attenuating affects over all concentrations. Compound 5e caused greater cell proliferation when compared to the control.ConclusionThese multifunctional compounds exhibited significant neuroprotective effects against neurotoxins, especially against Aβ 25 – 35. The compounds have shown promising activity as potential anti‐Alzheimer’s agents.