bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidomain interventions for dementia risk reduction: Can we detect a change in the signal?
Authors: Lussier Isabelle , Guillemont Juliette , Bacon Simon L , Boivin Michel , Ferland Guylaine , Lavoie Kim , Paré Guy , Belleville Sylvie 
Published: December 2021

AbstractBackgroundThere is increasing evidence that modifiable lifestyle factors account for around 40% of worldwide dementia cases. Given the multifactorial etiology of dementia, multidomain lifestyle interventions have generated major interest. Results from randomized controlled trials (RCTs) suggest that implementing multidomain interventions in at‐risk individuals is an effective strategy to delay disease onset. As per the Obesity‐Related Behavioral Intervention Trials (ORBIT) model, to ensure successful interventions, pre‐efficacy trials are needed to ascertain that each intervention component can yield a predefined clinically significant change (CSC). Therefore, the main objective of this Proof‐of‐Concept was to determine if each individual part of an online multidomain dementia risk reduction program can achieve a CSC in the targeted behavioural risk outcome.MethodThis was a 12‐week, within‐subject, treatment‐only study with three single‐domain groups (Diet, Physical Activity [PA] or Cognitive Engagement [CE]) and one multidomain group. The study enrolled cognitively healthy individuals aged 50‐70 with at least one risk factor among the targeted domains. The personalized intervention was delivered via a digital, coach‐supported application. Primary outcomes were the percentage of participants showing a CSC at study end in each domain. CSCs were defined as a change ≥ 1 point on the Canadian Mediterranean Diet Score, ≥ 300 METs‐min/week on the short version of the International Physical Activity Questionnaire, and ≥ 6 points on the Cognitive Activity Questionnaire, respectively. Additional outcomes comprised feasibility indicators.ResultThirty‐nine participants (mean age=63.1 [51‐68]; 82.1% female) were recruited, with 31 participants enrolled in the single‐domain groups (Diet, N=11; PA, N=7; CE, N=13). Within the single‐domain groups, participants received 7.9 (6‐9) coaching sessions. The number of participants achieving a CSC was 5 (45.5%) in the Diet group, 3 (42.9%) in the PA group and 6 (50.0%) in the CE group. Overall compliance and retention were 93.5% (89.6‐98.0) and 97.4% (92.3‐100), respectively.ConclusionThe results of this study support moving forward to the next ORBIT framework step, which includes refinement of the Luci intervention components and the design of a pilot feasibility trial to test the program in a larger sample of participants.
Analysis of recruitment planning for under‐represented participants in NIA‐funded Alzheimer’s disease and Alzheimer’s disease related dementias clinical trials
Authors: Han Sae H , Massett Holly A , Shakur Mujaahida , Lockett Jaron , Mitchell Alexandra K 
Published: December 2021

AbstractBackgroundInclusion of underserved participants is mandated by the National Institutes of Health (NIH), yet they remain under‐represented in NIH research, including Alzheimer’s and Related Dementias (AD/ADRD) clinical trials. Diverse representation is critical in AD/ADRD trials as African Americans (AA) and Hispanics/Latinos (H/L) are disproportionately affected by the disease. Research indicates that a priori recruitment planning is critical to successful recruitment into trials. This abstract analyzes the planned inclusion enrollment reports (IERs) and recruitment strategies described in grant applications for active National Institute on Aging (NIA)‐funded AD/ADRD clinical trials (N=271)MethodThis analysis used two methods: 1) documented the planned IERs for each NIA‐funded AD/ADRD clinical trial (active as of 10/16/2020); 2) conducted content analysis documenting: a) justification for IER, b) presence of a plan (yes/no), c) key enrollment strategies proposed (overall and for under‐represented populations), and d) quality of proposed recruitment planning (intercoder reliabilities: 80‐90%).ResultAcross the trials, median percent of total enrollment goal by IER categories were: Non‐Hispanic (91%) vs. Hispanic (9%); White (74%), AA (16%), Asian (4%), Other Races (2%). The top reason (62%) justifying trials’ IERs was “proportions represents trial site demographics.” Only 5% reported “proportions represent disease studied.” Most trials (91%) provided recruitment plans; however, 55% included no strategies specific to recruiting under‐represented populations. The majority (52%) of plans were rated medium quality (2‐3 strategies); the remaining were equally split between low and high quality (24% each). A median of 2 recruitment strategies were listed per trial; top strategies were: 1) traditional advertisements, 2) underserved‐focused community outreach, and 3) provider referrals. Additional analyses will be reported by intervention type, trial phase, and site type.ConclusionOur findings show inclusion planning for active NIA AD/ADRD clinical trials is heavily weighted towards non‐Hispanic Whites. Even if trials meet their IER goals, they will be under‐enrolling H/L, Asians, and Other Races as compared to the US Census data (2019). Most trials have recruitment plans, though not focusing on strategies targeted at recruiting those under‐represented. NIA should consider developing more robust guidelines to ensure grant applications have targeted, achievable, evidence‐based minority recruitment goals and plans set a priori.
Tau‐load in the lingual gyrus impacts anxiety levels during the COVID‐19 pandemic in participants of longitudinal observational studies in aging
Authors: Servaes Stijn , Lussier Firoza Z , Bezgin Gleb , Wang Yi‐Ting , Stevenson Jenna , Tissot Cécile , Elgbeili Guillaume , Arias Jaime Fernandez , Therriault Joseph , Benedet Andréa Lessa , Chamoun Mira , Pascoal Tharick A. , Bzdok Danilo , King Suzanne , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2021

AbstractBackgroundBy obtaining a better grasp on the impact of the COVID‐19 pandemic on individuals with cognitive impairment, this knowledge could be used to improve the delivery of information to this particular group. We aimed to assess the relationship between tau deposition and the change in anxiety levels, before and during the pandemic. We hypothesized that since the pandemic, higher tau loads would lower the change in anxiety. Furthermore, we expected these anxiety levels not to be associated with COVID‐19 related stress in participants with cognitive decline.Methods63 participants of the Translational Biomarker of Aging and Dementia (TRIAD) cohort (cognitively healthy, N=38; cognitively impaired, N=25, of which 7 had dementia due to Alzheimer’s disease), were assessed to evaluate their individual change in anxiety levels (GAD‐7). This was done at three different timepoints, of which the latest fell during the COVID‐19 lockdown period. Two rates of change, one before and one during the pandemic, were determined using the following definition: (next timepoint – current timepoint)/time difference. In addition, at the latest timepoint, subjective stress due to COVID‐19 was measured using the Montreal Assessment of Stress related to COVID‐19 (MASC). To assess the levels of tau, standard uptake value ratios (SUVR) from previously obtained [18F]MK‐6240 PET‐scans were used.Results[18F]MK‐6240 tracer binding in the lingual gyrus was negatively associated with the rate of change in GAD‐7 scores after correcting for age, sex, years of education and the presence of APOE ε4, but only in cognitively impaired individuals during the pandemic (fig 1A). In addition, the GAD‐7 score at the latest timepoint was associated with stress related to COVID‐19, but only in cognitively healthy individuals (fig 1B and 1C).ConclusionsThe presence of tau in the lingual gyrus negatively affected the rate of change in GAD‐7 scores during the COVID‐19 pandemic in individuals with cognitive impairment. This could indicate that information pertaining to the pandemic does not reach these individuals in an efficient manner. The missing association between COVID‐19 induced stress and the latest GAD‐7 scores in these individuals is a further indication of this.
The use of cognitive measures in older adults with concurrent hearing and vision impairment: A scoping review
Authors: Dumassais Shirley , Aubin Gabrielle , Jaiswal Atul , Gupta Shikha , Santhakumaran Sangeetha , Wittich Walter 
Published: December 2021

AbstractBackgroundOlder adults with dual sensory impairment (DSI/combined hearing and visual impairment), are more likely to obtain poorer scores on cognitive tests. Whether these results are due to poor cognitive function or inappropriate or absent adaptation of test administration for sensory impaired older adults is unclear. Given that this population is at higher risk of developing dementia, e.g., due to Alzheimer’s disease, ensuring optimal test administration is imperative to provide adequate cognitive care. Therefore, we mapped the existing scientific literature on various cognitive measures/tools that have been used to screen or assess cognitive impairment in older adults with DSI.MethodA scoping review was conducted using the Arksey and O’Malley framework (2005). Scientific articles were searched across eleven databases (CINAHL, Embase, Global Health, Mednar, OAIster, OpenGrey, PsycEXTRA, PsycINFO, PubMed, Web of Science, and WorldWideScience). The inclusion criteria were: the articles considered and/or measured cognitive function, in individuals with DSI, aged 65 and older. Extracted data included sample cognitive status, cognitive measure type (objective or subjective), reported cognitive domains evaluated by the measure, psychometric properties as well as reported, if any, sensibility measures during administration.ResultOf 11,595 articles retrieved, fifty‐six (n = 56) met the inclusion criteria. All but five (n=5) studies employed an objective measure of cognitive function. The most commonly used cognitive test in studies with older adults with DSI is the Mini‐Mental State Examination (1975) with almost 1/3 of the studies reporting its use (n=17). More importantly, none of the studies in this scoping review used cognitive tests that were adapted for vision and hearing impairment, highlighting that optimal cognitive assessment in DSI is neglected.ConclusionMost objective cognitive tests include vision‐ and hearing‐dependent items and require functional vision and/or hearing for both the administration and the execution of these tests. Our study confirmed the use of commonly used standardized tests, initially validated in a healthy population, to measure the cognitive function of older adults with DSI. Identifying these generally utilized tools is the first step to developing optimal adaptations in their administration for this vulnerable population.
Platform extension for second‐generation Elecsys β‐amyloid(1−42), pTau, and tTau cerebrospinal fluid (CSF) immunoassays on cobas e analyzers
Authors: Rutz Sandra , Wittig Martina , Geiselmann Gudrun , Müller‐Hübner Laura 
Published: December 2021

AbstractBackgroundThe Elecsys® β‐Amyloid(1−42) CSF Gen2 (Abeta42 Gen2), Phospho‐Tau (181P) CSF Gen2 (pTau Gen2), and Total‐Tau CSF Gen2 (tTau Gen2) immunoassays currently in development for the detection of Alzheimer’s disease will become available on cobas e 801 and e 402 platforms (Roche Diagnostics International Ltd). This study evaluated the analytical performance of second‐generation Elecsys CSF immunoassays on extended cobas e platforms.MethodCSF samples were analyzed using the Elecsys Abeta42 Gen2, pTau Gen2, and tTau Gen2 CSF immunoassays on cobas e 801 and e 402 analyzers at the Roche Penzberg site. Repeatability and intermediate precision were evaluated per the CLSI EP05‐A3 protocol using two assay‐specific PreciControl samples and a panel of native CSF samples covering the assay measuring range (two runs per day with two aliquots over 21 days; n=84). Coefficients of variation (CVs [%]) and standard deviations were calculated. Method comparisons (lot‐to‐lot and between platform) were conducted according to the CLSI EP09 protocol. For the lot‐to‐lot comparison, native CSF samples were analyzed for Lot A and B with all three Elecsys immunoassays on cobas e 801. For the platform comparison, native CSF samples were analyzed with all three Elecsys immunoassays on cobas e 801 and e 402. Passing‐Bablok regression and Pearson’s correlation were calculated.ResultGood precision was observed for all three Elecsys CSF immunoassays on cobas e 801. CVs for repeatability were ˂5% for Elecsys Abeta42 Gen2 and ˂2% for Elecsys pTau Gen2 and tTau Gen2, and for intermediate precision were ˂6%, ˂3%, and ˂2% for Elecsys Abeta42 Gen2, pTau Gen2, and tTau Gen2, respectively (Tables 1‐3). Method comparison experiments demonstrated good lot‐to‐lot agreement on cobas e 801 (Pearson’s r: 0.999−1.000) and good platform agreement between cobas e 801 and e 402 (Pearson’s r: 0.999−1.000) (Table 4). Broader on‐board and calibration stability were observed for the Elecsys CSF immunoassays on cobas e 801 and e 402 compared with cobas e 601 (data not shown).ConclusionSecond‐generation Elecsys CSF immunoassays demonstrated good analytical performance on extended cobas e platforms, including good precision, lot‐to‐lot and platform agreement, supporting their use and the implementation of CSF biomarkers in clinical routine.
Patient preferences for prognostic counseling in idiopathic/isolated REM sleep behavior disorder
Authors: Gossard Thomas R , Teigen Luke N , Timm Paul C , Feemster John C , McCarter Stuart J , St. Louis Erik K 
Published: December 2021

AbstractBackgroundTo examine patient preferences regarding prognostic counseling for idiopathic/isolated REM sleep behavior disorder (iRBD). Idiopathic/isolated REM sleep behavior disorder (iRBD) carries an approximate 73‐91% long term risk for phenoconversion to dementia with Lewy bodies (DLB) and Parkinson disease (PD). Previous research has shown that most providers counsel their patients concerning this risk, yet patients’ values and preferences regarding counseling are unknown.Methods122 participants with iRBD in the Mayo Clinic iRBD Patient Registry enrolled. Participants were sent a survey concerning prognostic counseling and their experience in being diagnosed with iRBD.ResultsOf 81 respondents (67.2% response rate), 74% were men with an average age of 65.7 ± 9.7 years. Responses indicated a strong preference toward receiving prognostic information; 92.5% felt knowledge concerning neurodegenerative disease risk was important, while 87.6% felt prognostic discussion was important to maintain trust in their physician. Additionally, 95.7% indicated they desired more information, while only 4.3% would have desired less information regarding prognostic risk following iRBD diagnosis. Most respondents agreed strongly that prognostic information was important for discussions with their family and friends and future life planning, and expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia.ConclusionsiRBD patients indicated a strong preference for disclosure of neurodegenerative prognostic risk information, preferred more rather than less information, and felt prognostic information was important for family discussions and life planning. This data informs prognostic counseling practices regarding iRBD and other neurodegenerative diseases.
Clinical and analytical comparison of three assays for plasma p‐tau isoforms on an ultrasensitive platform
Authors: Bayoumy Sherif , Dulk Ben Den , Hussainali Zulaiga , Verberk Inge M.W. , van der Flier Wiesje M , Zwan Marissa D. , Dage Jeffrey L. , Teunissen Charlotte E. 
Published: December 2021

AbstractBackgroundPlasma phosphorylated Tau (P‐tau) protein is a promising biomarker for early detection of Alzheimer’s Disease (AD), reflecting abnormal tau metabolism in CSF and brain. Different Tau isoforms have been shown as specific biomarkers to detect AD including plasma tau phosphorylated at threonine 181 (P‐tau181) and at threonine 217 (P‐tau217). Novel plasma tests have been developed on various platforms for different isoforms and using various reagents, but these have not been compared directly for their analytical and clinical performance. In this study, we directly compared three novel P‐tau blood assays to investigate the clinical and technical differences between each assay.MethodWe included the following assays: plasma P‐tau181 from Quanterix, P‐tau181 Lilly and P‐tau217 Lilly assays, all run on the Simoa HD‐X (Quanterix). We analytically compared the novel assays for the parameters: precision, linearity, parallelism, limit of detection, recovery and sensitivity. The clinical performance of each assay was evaluated using plasma samples from 40 non‐demented healthy individuals of www.hersenonderzoek.nl (median age 66 years, 68 % females) and 40 AD‐dementia cases of the Amsterdam dementia cohort (median age 66, 60 % females). Using a receiver operating characteristics (ROC) curve analysis, we compared the discriminatory ability of each assay. Here, we present the clinical performance results.ResultPlasma P‐tau217 and both plasma P‐tau181 assays were highly correlated, with correlation coefficients over 0.82 (all p< 0.001). Patients with AD‐dementia showed elevated levels of P‐tau181 and P‐tau217 in comparison to healthy controls (P‐tau 217 AUC = 0.995 (0.986‐1.00), P‐tau181 Quanterix AUC=0.936 (0.885‐987), P‐tau 181 Lilly AUC= 0.938 (0.87‐1.00)). The P‐tau217 Lilly assay numerically outperformed both the P‐tau 181 assays in discriminating between AD‐dementia and control cases with a sensitivity of 97.5% at a specificity of 95%. The P‐tau181 Quanterix and Lilly showed a sensitivity of 100% at 89.5%, 79% specificity, respectively.ConclusionOur findings suggest that the novel plasma P‐tau isoform tests are useful for the diagnostic work up of AD‐dementia.
AlzPED: Optimizing the predictive power of drug efficacy studies in Alzheimer’s disease animal models
Authors: Chakroborty Shreaya , Sharma Ali , Martin Zane , Yuan Jean , Petanceska Suzana S , Refolo Lorenzo M 
Published: December 2021

AbstractBackgroundPoor translation of preclinical efficacy from animal models to the clinic is a major challenge to successful therapy development for Alzheimer’s disease (AD). Assessments of preclinical animal studies highlight the need for an emphasis on rigor in study design and methodology and a consensus towards a uniform set of study design elements and best practices. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), a searchable and publicly available knowledgebase developed by the National Institute on Aging, has identified and compiled a standardized set of best practices and experimental design guidelines to effectively promote the translation of preclinical therapeutic studies in AD animal models to the clinic.MethodUsing key word‐driven literature searches published studies are acquired and curated by two experts for data on authors, funding source, AD animal models, therapeutic targets and therapeutic agents, study design, and outcome measures, prior to publication in the database. Rigor in study design and methodology is evaluated with a Rigor Report Card consisting of a standardized set of expert‐recommended study design elements.ResultAlzPED hosts curated summaries from more than 1100 published preclinical therapeutic studies in AD animal models, and data related to 223 therapeutic targets, 1020 therapeutic agents, 200 animal models, more than 1500 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from each study demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation, blinding for treatment, blinding for outcomes, randomization, balancing for sex, animal genetic background, and inclusion/exclusion criteria, these being reported by fewer than 30% of the more than 1100 curated studies.ConclusionAnalysis of curated studies demonstrates serious deficiencies in reporting critical elements of methodology. These deficiencies diminish the scientific rigor, reproducibility, and translational value of the preclinical studies. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of preclinical drug testing data to the clinic.
Amelioration of tau related pathology with a novel anti‐prion protein monoclonal antibody in an AD mouse model
Authors: Boutajangout Allal , Zhang Wei , Abdali Wed , Kim Justin Sung Tae , Prelli Frances , Wisniewski Thomas 
Published: December 2021

AbstractBackgroundA number of studies have shown that amyloid β oligomers (Aβo) mediate their toxicity, in part, via the cellular prion protein (PrPC) on the surface of neurons. We hypothesized that tau oligomers may also mediate toxicity and spread of pathology via PrPC. We have generated a novel monoclonal anti‐PrP antibody (TW1) and assessed the efficacy of passive immunization with this antibody in a mouse model of AD with only tau related pathology.MethodHTau/PS1 transgenic AD model mice were injected at 5 months of age intraperitoneally once a week with TW1 from the age of 5 months. Control mice received only saline. Their behavior was assessed at 8 months of age and brain tissue subsequently harvested for analysis at 9 monthsResultThe treated and control mice did not show any significant differences in sensorimotor testing. Significant statistical differences were observed with the novel object recognition test in the immunized mice on percentage time spent in zones (two tailed, t‐test p = 0.0019). On the closed field symmetrical maze immunized mice performed significantly better (Day1: two tailed t‐test p=0.0001; Day2: two tailed t‐test p=0.0015; Day3: two tailed t‐test p=0.0002). Fifty percent less tau pathology was observed in the dentate gyrus with PHF‐1 immunolabeling (two tailed t‐test p= 0.02) and a 60% reduction was seen in the piriform cortex (two‐tailed, t‐test p=0.01) in treated vs control animals. CP13 immunolabeling showed a significant difference in the piriform cortex (p=0.02, two‐tailed t‐test) in treated mice versus controls. There was no significant difference in astrogliosis or microgliosis in treated versus control mice. Western blots using PHF‐1 showed that TW1 therapy reduced phosphorylated tau pathology (two‐tailed t‐test p=0.03) and improved the ratio of pathological soluble tau to tubulin (two‐tailed t‐test p=0.0006). The same effect were observed with the CP13 antibody (two‐tailed t‐test p=0.0007) and improved the ratio CP13/tubulin (two tailed, t‐test p=0.0014).ConclusionThese results indicate that passive immunization with the TW1 antibody can significantly decrease tau pathology and improve cognition in a transgenic mouse model of AD.