bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within‐ and Between‐Session Changes on Motor Learning and Amyloid Status
Authors: Duff Kevin , Schaefer Sydney Y , Hoffman John M. 
Published: December 2023

AbstractBackgroundThere is a growing body of literature that suggests that motor learning may be indicative of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). For example, motor learning may provide unique information for enriching clinical trials in MCI and AD if it is related to biomarkers of interest. The current study sought to examine motor learning patterns relative to amyloid deposition in the brain.MethodOne hundred fifty‐four older adults who were cognitively intact or had amnestic MCI or mild AD participated. Each participant completed a motor learning task that consisted of six trials of moving beans with a spoon between three cups, and the total time to complete the task was measured. This task was repeated at two additional visits, about one week and one year later. Each participant also completed an amyloid positron emission tomography (PET) scan within a month of the motor testing. Based on FDA‐approved prescribing and visual interpretation information, the amyloid PET scan was classified as positive (n = 94) or negative (n = 60). A second repeated‐measures analysis examined trial one at the initial, one‐week, and one‐year visits to look for between‐session changes based on amyloid status.ResultWithin the initial visit, both groups significantly improved their response time on this motor learning task across the six trials (p<0.001) and those classified as amyloid negative performed significantly faster than their amyloid positive peers (p = 0.01). However, there was no significant time by amyloid status interaction (p = 0.92). Like in the within‐session results, there were main effects of time (p<0.001) and amyloid status (p = 0.003), but there was not a significant interaction of the two (p = 0.37).ConclusionOlder individuals who are amyloid positive performed worse on this motor learning task than their amyloid negative peers, both within the same session and between sessions. Additionally, notable learning was present in both groups within the same session, but this was somewhat reduced in the amyloid positive individuals across sessions. Even though there was no clear interaction between time and amyloid status, motor learning tasks may provide unique information in identifying individuals for clinical trials who are more likely to be amyloid positive.
Evolution of behavioral and psychological symptoms of dementia in the logopenic variant of primary progressive aphasia
Authors: Tastevin Tastevin , Laforce Robert , Lavoie Monica , Poulin Elizabeth , Sablonnière Justine De La , Carrier‐Auclair Julie 
Published: December 2023

AbstractBackgroundThe logopenic variant of primary progressive aphasia (lvPPA) is known to be associated with behavioral and psychological symptoms of dementia (BPSD) such as depression and apathy. However, few data are available regarding the evolution of BPSD, particularly in advanced stages and end of life, which is often of great concern for patients and families.MethodWe performed a retrospective chart review in a cohort including 42 deceased patients with a diagnosis of lvPPA. Symptoms of BPSD were assessed from disease onset to death by three experienced raters and, when possible, interviews were performed with proxies of patients to complete the missing data.ResultDepression and anxiety were mostly prevalent at the early stages but decreased over time. In particular, at one‐year after first visit, 36% of the patients were affected by anxiety symptoms and 19% were suffering from depressive symptoms. Apathy increased with the follow‐up with a peak at 5 years from the first clinical visit (46% of the patients). Other BPSD such as rituals, hyperorality, or agitation were less prevalent throughout the disease. Nevertheless, patients frequently presented with dishinibition during the follow‐up (between 20‐36% of the patients during the 5 years following the first visit).Antidepressants were used in around 20‐28% of the patients from first visit to later stages, followed by anxiolytics (3‐22%). Antipsychotics were mostly used in the advanced stages. At the first visit, 42% of the patients were treated with acetylcholinesterase inhibitors. During the follow up, this rate fluctuated between 40‐64%.ConclusionAffective symptoms were most prevalent in prodromal and early stages, whereas in the advanced stages, lvPPA was mostly characterized by apathy. Dishinibition was also frequent during the follow‐up. These findings could support a psychiatric assessment in the early stages, since depression and anxiety are known to respond well to psychotropic treatment.
An Automated Montreal Cognitive Assessment MoCA‐Report for Optimal Clinical Management of Alzheimer’s Disease and Initial Eligibility Assessment for Newly Approved Therapies
Authors: Klil‐Drori Sivan , Bodenstein Katie C , Ghantous Youssef , Nasreddine Ziad S 
Published: December 2023

AbstractBackgroundThe Montreal Cognitive Assessment (MoCA) is one of the cognitive screening tools most frequently used in primary care. Early detection of Alzheimer’s disease will allow rapid intervention, including initiation of recently approved disease modifying therapies, which carry potential benefits for patients, e.g., maintained cognition and function, along with improved prognosis. However, patients with cognitive impairment detected in primary care are commonly referred to specialty clinics for further evaluation. This causes large volume of referrals and long waiting‐time to cognitive specialists which delay diagnosis and treatment. Therefore, an automated report of cognitive screening with rapid interpretation of the results may allow primary care clinicians to identify the patients with high probability for Alzheimer’s disease and potential eligibility to approved therapies.MethodWe completed an extensive literature review and gathered data derived from the MoCA that is relevant for clinical management and suitability for approved disease‐modifying therapies. Following this, we developed an automated report for the digital‐MoCA software that will present pertinent information that is applicable for clinical management, staging, conversion to other useful well‐known scales, and initial assessment of eligibility for approved disease modifying therapies.ResultBased on published studies, we developed a detailed MoCA‐Report to be automatically generated upon completion of the digital‐MoCA. The MoCA‐Report presents the patients’ score on each subtest as well as the total score in comparison to normative data, the Memory Index Score (MIS), MoCA score conversion to Clinical Dementia Rating Scale, Mini Mental State Examination, and risk for amyloid pathology. The MoCA‐Report also includes relevant information on staging, risk for driving errors, and possibility of conversion to dementia. It is designed to provide primary care clinicians assistance in clinical management, initial identification of eligibility for disease modifying therapies, and selection of referrals to specialty clinics, thus improving patient care and supporting the healthcare systems.ConclusionThe MoCA‐Report integrates information and interpretation of cognitive screening in an automated modality, with minimal use of staff and time. Rapid interpretation of the cognitive screening in primary care may support clinical management in a timely manner and promote early detection and intervention for patients with Alzheimer’s disease.
The influence of Area Deprivation Index on cognition in cognitively‐normal adults as measured by Principal Component Analysis of Neuropsychological Data
Authors: Conner Drew C , Botchway Albert , Scaife Steve , Unnam Pavani , Roller Hunter R , Zec Ronald F , Ala Tom , Hascup Erin R. , Trivedi Mehul Alkesh 
Published: December 2023

AbstractBackgroundPrevious research has demonstrated that neighborhood disadvantage is associated with worse health outcomes including increased risk for dementia. The Area Deprivation Index (ADI) measure represents the theoretical domains of income, education, employment, and housing quality, which allows for the ranking of neighborhoods based on socioeconomic disadvantage. In the present study, we hypothesized that greater neighborhood disadvantage (i.e., higher ADI scores) would be associated with lower cognitive function after controlling for age, education, and sex.MethodPrincipal component analysis (PCA) was used to examine the component structure of a neuropsychological test battery administered to 852 adult participants enrolled in the Southern Illinois University Longitudinal Cognitive Aging Study (SIU LCAS). The vast majority of the cohort was White/Not Hispanic (>98.0%) and female (72.4%). Mean age and education were 67.5 years and 14.8 years, respectively. Linear regression analysis was used to examine the relationship between ADI and PCA cognitive component scores after controlling for age, education, and sex.ResultPCA identified four cognitive components, which were labeled speed/flexibility, visuospatial skills, word list learning/memory, and story memory (immediate and delayed recall). Regression analysis revealed that all three demographic variables were significantly associated with each cognitive component score (p<0.001). After controlling for age, gender, and education, higher ADI scores were associated with lower cognitive component scores for only the speed/flexibility component (p = 0.03). Age, education, and sex accounted for 23% of the variance in the speed/flexibility component. ADI accounted for only an additional 0.4% of the variance in the speed/flexibility component. There was no significant relationship between ADI scores and the visuospatial skills, word list learning/memory, and story memory components.ConclusionOur results suggest that the relationship between greater neighborhood disadvantage and poorer cognitive function are very subtle and may only be present for some, but not all, cognitive domains. One major limitation in the present study was that collection of cognitive data and ADI calculations were not synchronous. More studies are needed to better understand the relationship between neighborhood disadvantage and cognitive functioning.
Estimating the prevalence of mild cognitive impairment from clinical notes in U.S. Veterans
Authors: Jasuja Guneet , Li Xuyang , Aguilar Byron J. , Shishova Ekaterina , Morin Peter J , Berlowitz Dan , Miller Donald R , O'Connor Maureen K. , Nguyen Andrew H. , Zhang Raymond , Monfared Amir Abbas Tahami , Zhang Quanwu , Xia Weiming 
Published: December 2023

AbstractBackgroundIndividuals with mild cognitive impairment (MCI), a noticeable decline in cognitive abilities, are at increased risk of developing Alzheimer’s disease (AD) or other dementia. Risk factors for dementia, such as obesity, stroke, depression are highly prevalent among U.S. veterans We report on the trends in the prevalence of MCI using clinical notes over the past 5 years in the Veteran Affairs, the largest integrated healthcare system in the U.S.MethodPrevalent cases of MCI were identified from VA clinical notes for all Veterans aged 50 years and older in VA care from fiscal years (FYs) 2015‐19. VA clinical notes are maintained in searchable text integration utility files (TIU) available in the VA Corporate Data Warehouse (CDW). Pharmacy clinical notes were excluded. “Mild cognitive impairment” keyword was searched in clinical notes to identify patients with MCI. We validated the keyword “mild cognitive impairment” in 199 clinical notes. The positive predictive value for this validation was approximately 91%. For each FY, age and sex adjusted rates directly standardized to the 2010 U.S. Census general population were estimated.ResultA total of 308,930 prevalent cases of MCI were identified from VA clinical notes from FYs 2015‐19. Standardized prevalence rates for MCI increased steeply, with prevalence of 0.9% in FY 2015, increasing to 1.31% in FY 2019. Standardized age adjusted MCI prevalence rates also increased sharply for male (0.77% in FY 2015 to 1.10% in FY 2019) and female veterans (1.01% in FY 2015 to 1.50% in FY 2019) with rates higher for females than males for each FY.ConclusionWe observed recent trends of increasing prevalence rates for MCI among veterans identified from VA clinical notes. Considering the increased risk of dementia among individuals with MCI, our study finding of increasing prevalence of MCI among veterans highlights the critical need for effective interventions and treatment to target veterans with MCI.
Radiopharmaceutical selection for tau PET imaging
Authors: Ozsahin Ilker , Onakpojeruo Efe Precious , Uzun Berna , Ozsahin Dilber Uzun , Butler Tracy A 
Published: December 2023

AbstractBackgroundThe accumulation of pathologically misfolded tau is a feature that is shared by a group of neurodegenerative disorders that are collectively referred to as tauopathies. AD is the most prevalent of these tauopathies. Neurofibrillary tangles are characterized by the presence of hyperphosphorylated protein (tau), and senile plaques are characterized by the presence of amyloid peptide aggregates. PET imaging is fully quantitative and enables accurate spatial assessment. However, as a result of non‐specific binding and the limited spatial resolution of PET scanners, this technique requires not only the presence of tau inclusions in a brain region but also sufficient density and spatial extent of those inclusions in order to generate a sufficient signal‐to‐noise ratio. With the development of tau‐specific ligands for use with PET, it is now possible to investigate the role that tau pathology plays in the development and progression of these disorders. The purpose of this study is to analyze, compare, and rank the currently available tau PET tracers for imaging in research and routine clinical settings.MethodWe proposed using the fuzzy Preference Ranking Organization Method for Enrichment of Evaluations (PROMETHEE), a multicriteria decision‐making (MCDM) tool. First‐generation tau PET tracers ([18F]AV1451, [11C]PBB3, [18F]THK5117, [18F]THK5351, [18F]THK5317, and [18F]THK5105) and second‐generation compounds ([18F]MK‐6240, [18F]JNJ‐067, [18F] PI‐2620, [18F]RO‐948 (previously referred to as [18F]RO69558948), [18F]PM‐PBB3, [18F]GTP1, [18F]JNJ‐64349311 ([18F]JNJ311), [11C]RO‐6931643, and [11C]RO‐6924963) were selected to investigate in this study. The evaluation is based on relative parameters, such as specificity, target binding accuracy, neocortical uptake, radiation exposure, brain penetration, free fraction in plasma, defluorination, and adverse reactions, and the importance that is placed on each of these parameters is weighted differently.ResultThe results from this study show that [18F]RO‐948 is the most favorable tau PET ligand, while[18F]THK5105 is the least favorable one based on the considered weighted criteria in this study.ConclusionFuzzy PROMETHEE can be used as a decision‐aid system to select the proper radiopharmaceuticals for tau PET imaging. This study can be extended to include more tracers and criteria and might help researchers and concerned readers to select the optimal tau PET tracer.
Proposal for Efficient Access to Cognitive Screening: using MoCA‐XpressO Pre‐screen, MoCA‐Duo Videoconference Screen, and MoCA‐Report for Post‐screen Interpretation
Authors: Klil‐Drori Sivan , Bodenstein Katie C , Ghantous Youssef , Nasreddine Ziad S 
Published: December 2023

AbstractBackgroundThe continuously aging population worldwide results in increased prevalence of cognitive decline and growing demand for cognitive screening. This demand is expected to increase with newly approved disease modifying therapies. However, scarce resources for professional cognitive assessments, requires efficient screening tools that are accessible and easily applied. Therefore, a simple process of brief self‐administered cognitive pre‐screening, videoconference‐screening, and an automated report with result interpretation, may be highly efficient and will increase access to cognitive screening.MethodWe integrated validated novel tools for accessible, home‐based cognitive pre‐screening and screening. It includes development and validation of the Montreal Cognitive Assessment (MoCA)‐XpressO: a brief self‐administered cognitive pre‐screening tool, and cognitive screening via MoCA‐Duo: videoconference version of MoCA. Finally, we developed the MoCA‐Report, an automated summary of MoCA‐Duo with result interpretation according to various cognitive domains and suggestions for further inquiries.ResultThe MoCA‐XpressO includes assessment of memory tasks, logical tasks, and processing speed. Validation of MoCA‐XpressO showed high accuracy (AUC 0.85) therefore may identify the healthy population with no objective cognitive impairment: the “worried‐well” who will not require further screening. Cognitive screening can then be applied via MoCA‐Duo only to selected patients with identified cognitive impairment. MoCA‐Duo by videoconferencing carries significant benefits: (1) allows home‐based validated assessment; (2) allows matching between patients and certified raters across the globe, with similar country of origin and language, which is highly valuable in cognitive evaluations. Ultimately, post‐screening interpretation is provided automatically by MoCA‐Report which presents interpretation of the scores according to normative data, present the Memory Index Score (MIS), conversion to Mini Mental State Examination and Clinical Dementia Rating scores, optional cognitive manifestations, prediction of conversion to dementia, prediction of amyloid pathology, and potential risk for driving errors. It will also explore potential eligibility for newly approved disease modifying therapies.ConclusionThe estimated increase in the prevalence of dementia, and newly approved disease modifying therapies are expected to increase demand for cognitive screening. Integration of self‐administered cognitive pre‐screening by MoCA‐XpressO, and videoconference cognitive screening via MoCA‐Duo including an automated report with result interpretation, propose efficient and comprehensive cognitive screening for high volume of patients.
A novel approach to measure dyadic patterns of subjective cognitive changes: its association to Alzheimer’s disease biomarkers and ability to predict clinical progression in cognitively normal older adults
Authors: Vannini Patrizia , Gagliardi Geoffroy Pierre , Cacciamani Federica , Mimmack Kayden J. 
Published: December 2023

AbstractBackgroundDiscrepancy in the dyadic relationship of subjective cognitive change has revealed both increased/heightened awareness and decreased awareness/unawareness in the predementia stages of Alzheimer’s Disease (AD). The dyadic relationship is often calculated using the mean discrepancy between an individual and their study partner’s scores on a memory complaints questionnaire. However, participants may display heightened awareness on some questions and unawareness on others, canceling out each other’s effect and masking subtle changes in either direction. Here, we present a new item‐level methodological approach allowing us to examine individual subtle changes in these two awareness dimensions separately. Moreover, we compared them to AD pathology and investigated their ability to predict clinical progression.MethodA total of 503 ADNI participants (Table.1) with baseline clinical dementia rating (CDR) = 0 and baseline CSF (Aβ1‐42 and t‐tau) were included. A subset (N = 329) had at least two follow‐up CDR time points to compute clinical progression. A traditional score was calculated as the average discrepancy between the partner and participant’s responses on the Everyday Cognition questionnaire, with positive scores indicating heightened awareness and negative scores indicating unawareness. An unawareness (resp., heightened awareness) sub‐score was computed by applying a ceiling (resp., floor) at zero to item‐level differences before averaging. Each measure was compared by AD pathology, adjusted for age and sex. Survival analyses examined the relationship of the new scores with clinical progression.ResultCSF t‐tau, but not Aβ1‐42, was a significant independent predictor of the traditional and unawareness scores in models adjusting for each other. There was no significant interaction between the two (Table.2). Survival analyses showed a one‐point improvement on the unawareness sub‐score associated with an 84% reduction in progression hazard (HR = 0.16, p<0.001), or equivalently. A one‐point decline and 525% increase in progression hazard, with no significant effect for the heightened awareness score.ConclusionDecomposing the traditional awareness score into two sub‐scores, allowed the investigation of the relationship between AD and awareness with more specific, sensitive measures. Of these, the unawareness sub‐score was associated with t‐tau and a strong predictor of clinical progression, providing further support that discordant self‐ and informant‐reported cognitive decline may provide important clinical information.
Dyadic patterns of subjective cognitive decline relate to Alzheimer’s disease biomarkers differently in preclinical and prodromal clinical states
Authors: Houston Michelle L , Zhang Panpan , Liu Dandan , Hohman Timothy J. , Blennow Kaj , Zetterberg Henrik , Jefferson Angela L. , Gifford Katherine A. 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) may provide an early indicator of evolving neurodegenerative disease. Dyadic SCD patterns, or understanding the self/patient’s in relation to an informant/loved one’s endorsement of SCD, may more accurately reflect underlying Alzheimer’s disease (AD) pathology in particular. We related dyadic discrepancies in SCD to markers of core AD pathology, including amyloid‐β42 (Aβ42) and phosphorylated tau (p‐tau).MethodVanderbilt Memory and Aging Project participants free of clinical dementia [n = 150, 72±7years, 37% mild cognitive impairment (MCI)] and their informants completed the Everyday Cognition questionnaire. Dyadic discrepancy (self‐reported score minus informant‐reported score) was calculated. Positive scores indicate self>informant SCD and negative scores indicate informant>self SCD. Participants also underwent fasting lumbar puncture to obtain cerebrospinal fluid (CSF) for quantification of Aβ42 and p‐tau. Linear mixed‐effects regression models related dyadic score to individual CSF biomarkers adjusting for age, sex, self‐reported race/ethnicity, cognitive status, apolipoprotein E‐ε4 status (positive, negative), and depression symptoms (Geriatric Depression Scale) with false discovery rate (FDR) corrections for multiple comparisons. Models were repeated with a diagnosis x biomarker interaction.ResultSCD discrepancy in the negative direction (informant>self‐SCD) was associated with higher CSF p‐tau (β = ‐0.64, pFDR<0.001). Cognitive status modified the association between discrepancy score and Aβ42 (β = 10.81, pFDR = 0.02). Stratified analyses by cognitive status revealed that MCI participants with negative discrepancies (informant>self‐SCD) had lower Aβ42 levels (β = 5.592, pFDR = 0.02), indicating more cerebral amyloid deposition. The opposite pattern was observed in cognitively unimpaired participants, though findings did not survive FDR correction (β = 1.16, p = 0.03, pFDR = 0.24). Additionally, in MCI participants, negative SCD discrepancy was associated with higher p‐tau levels (β = ‐0.7223, pFDR = 0.02). All significant results survived outlier exclusion. See Figure for details.ConclusionDyadic SCD discrepancy correlates with AD biomarkers differently in preclinical and prodromal states. In MCI, greater informant‐SCD related to more amyloid and p‐tau deposition, likely due to patient anosognosia and increasing functional changes noted by others. Conversely, in an earlier, preclinical stage before the onset of overt problems, more self‐SCD appears indicative of greater amyloid pathology. Results are consistent with the purported pathological cascade of AD and highlight the relevance of considering dyadic SCD to inform underlying disease.