bluuebunny/crossref_metadata_2025_split huggingface dataset:
The status of digital pathology and machine learning within Alzheimer’s Disease Centers
Authors: Dugger Brittany N. , White Charles , Stahly Brian , Schneider Julie A. , Robichaud Elizabeth , Reichard Ross R. , Prokop Stefan , Perrin Richard J. , Nelson Peter T. , Lieberman Andrew P. , Kukull Walter A. , Kofler Julia , Keene C. Dirk , Kapasi Alifiya , Irwin David J. , Flanagan Margaret E. , Crary John F. , Chan Kwun Chuen Gary , Murray Melissa E. ,   The Alzheimer's Disease Center Digital Pathology Working Group
Published: December 2020

AbstractBackgroundDigital pathology and machine learning (ML) workflows have paradigm shifting potential especially in the field of Alzheimer’s disease and related disorders. However, many institutions/centers may not have access to these technologies. To provide benchmark data, a survey was developed and distributed to National Institutes of Health’s Alzheimer’s Disease Centers (ADCs) in the United States.MethodSurvey questions covered topics such as: infrastructure (i.e. type of digital slide scanners used), funding sources (i.e. how the scanner was funded), and data management/storage (i.e. size of digital files). After development, review, and approval by the ADC digital pathology working group, the survey was distributed via email to 35 past and current ADC directors and/or ADC neuropathology core leaders. Participation in the survey was completely voluntary and answers did not contain any personal data.ResultThe survey generated over a 90% response rate, and the majority of those who completed the survey were neuropathology core leaders; 81% stated their ADC had access to a digital slide scanner, most common brand being Aperio/Leica. One third of respondents stated there was a fee for service to utilize the scanner. For digital pathology and/or ML resources, 40% of respondents stated none are supported in any way by their ADC. To cover the purchase and operation of the scanner, 50% stated they had institutional support. Many were unsure of the approximate average scanned file size of digital images (37%) and total amount of storage space that files occupied (50%). Many (75%) were aware of other departments at their institution working with digital pathology and/or ML, but a similar percentage was unaware of multi‐university or industry partnerships.ConclusionThese results demonstrate many ADCs have access to a digital slide scanner and had institutional support to cover the purchase. However, further investigation is needed to understand hurdles and barriers for implementing both digital pathology and ML workflows aiding in standardized methods across ADCs.
Monitoring disease pathophysiology longitudinally using multiparametric PET acquisitions: The McGill TRIAD cohort
Authors: Stevenson Jenna , Chamoun Mira , Benedet Andréa Lessa , Rahmouni Nesrine , Gagné Guylaine , Savard Mélissa , Cellucci Tasha Vinet , Poltronetti Nina Margherita , Pascoal Tharick A. , Lussier Firoza Z. , Tissot Cécile , Therriault Joseph , Stevenson Alyssa , Vitali Paolo , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2020

AbstractBackgroundThe Translational Biomarkers in Aging and Dementia (TRIAD) cohort aims at describing the biomarker trajectories and interactions between pathophysiological processes as drivers of dementia. While focusing on advanced personalized and preclinical dementia diagnosis, TRIAD’s main objectives include understanding the interactions between amyloid‐β and tau and their role in the progression of brain atrophy and cognitive decline; as well as the role of neuroinflammation, epigenetics and synaptic depletion as mediators of cognitive decline.MethodInclusion into the TRIAD cohort begins with a telephone screening ensuring the participant’s eligibility. Participants sign an ethically approved consent form where they agree to donate biofluids (blood, urine, saliva and cerebrospinal fluid) at the first on‐site visit. The second visit consists of an extensive neuropsychological battery, followed by PET and MRI visits. The PET scans completed are dependent on their diagnosis and the project in which they are enrolled. TRIAD cohort uses a variety of tracers in their different projects to detect the presence of different protein accumulation in the brain. These tracers include [18F]MK6240, [18F]AZD4694, [18F]AV1451, [18F]PI2620 and [18F]RO948, [11C]PBR28 or [18F]DPA, [18F]FEOBV [11C]MRT and [18F]SDM‐8. TRIAD participants complete intermediate telephone follow‐up calls at 6 and 18 months and return for follow‐up clinical and imagery visits 12 and 24 months after baseline, with a retention rate of 75%.ResultSince 2017, the TRIAD registry has recruited 1,285 people and enrolled 576 participants. Enrolled in the TRIAD studies are individuals without cognitive impairment (n=345), with mild cognitive impairment (n=75), sporadic and autosomal‐dominant Alzheimer’s disease (n=90), atypical dementia (n=27) and individuals under evaluation (n=39). The TRIAD cohort currently banks 495 baseline blood collections and 108 follow‐up collections with 85 participants having completed 12‐month follow‐up scans and neuropsychological evaluation.ConclusionWith a strong participant retention rate, TRIAD presents a striking opportunity to further understand the progression of Alzheimer’s disease with resources ready to uphold the use of affordable biomarkers, capable of diagnosing and measuring disease progression.
Defining longitudinal change on the auditory verbal learning test using a conditional normative model to account for practice effects: Preliminary validation in preclinical Alzheimer’s disease
Authors: Alden Eva , Lundt Emily S. , Christianson Teresa J. , Machulda Mary M. , Kremers Walter K. , Jack Clifford R. , Knopman David S. , Petersen Ronald C. , Mielke Michelle M. , Stricker Nikki H. 
Published: December 2020

AbstractBackgroundPractice effects can obscure interpretation of longitudinal cognitive performance. Reliable change indices (RCIs) provide data for determining a significant change, typically for a single repeat assessment, but multiple follow‐up visits are common clinically and in research cohorts. Further, regression‐based or linear mixed effects models improve prediction of future cognitive decline and have higher correlations with neuroimaging biomarkers than RCI approaches. We present norms for change for the Auditory Verbal Learning Tests (AVLT) with conditional normative z‐scores for up to 7 repeat assessments, and demonstrate application of this method to individuals with preclinical Alzheimer’s disease (AD).MethodNormative Sample: Robust conditional norms were derived from 1001 adults ages 50‐90 from the Mayo Clinic Study of Aging (MCSA) who completed the AVLT across 4‐8 visits approximately 15 months apart and remained cognitively unimpaired (CU) across all available visits. Linear mixed effects models were used to compute a conditional normative z‐score for AVLT 30‐minute recall and sum of trials. Models included adjustment for baseline performance, number of prior test exposures, demographic factors (age, sex, education), and interactions (baseline*time; sex*time). Test Sample: We used a preclinical AD sample with positive amyloid and tau imaging (n= 27 CU A+T+; Jack et al. 2017) expected to have a higher rate of intra‐individual cognitive decline relative to CU A‐T‐ individuals (n = 268) to compare mean performances of conditional normative z‐scores to typical age‐corrected Mayo’s Older Americans Normative Studies (MOANS) norms. Participants had at least 1 and up to 4 follow‐up visits, with their most recent AT data used for classification.ResultAVLT performance based on typical norms did not differ across A+T+ and A‐T‐ groups. Specifically, across 2‐4 follow‐up visits, the typical norms mean z‐score was similar across groups (p=0.945; see Table 1). However, the conditional norms mean z‐score that accounts for practice effects and typical trajectories of AVLT performance was lower in the A+T+ relative to the A‐T‐ group for 30‐minute recall (p=0.055) and sum of trials (p=0.060).ConclusionConditional normative methods that account for practice effects are more sensitive to preclinical AD than typical norms, and show promise for identifying transitional cognitive decline.
Association of the cognitive‐motor syndrome with the incidence of dementia
Authors: Vargas Anamaria Rosales , Acosta‐Castillo Gilberto Isaac , Sosa‐Ortiz Ana Luisa 
Published: December 2020

AbstractBackgroundThe cognitive‐motor syndrome (CMS) describes the association of cognitive and gait alterations, being potentially useful for predicting dementia. The criteria proposed for the CMS are: cognitive complaint, decrease in gait speed, preservation of daily life activities, and absence of dementia.MethodThis work is a population‐based cohort secondary analysis. We studied 1,823 adults older than 65 years, without dementia at the baseline evaluation. The follow‐up evaluation was done after three years. We first estimated the association of the CMS with sociodemographic and clinical variables, followed for the dementia incidence, using a cumulative incidence reasons model.ResultThe incidence of dementia cases was associated with the following sociodemographic variables: age, education level, and the number of assets and services at home. Regarding the clinical variables analyzed, we found that the incidence of dementia was associated with diabetes mellitus and depression.According to the cumulative incidence ratios, the patients that presented the cognitive‐motor syndrome have a risk ratio of 1.69 (95% CI: 0.68‐419) for developing dementia (p = 0.25).ConclusionAccording to the criteria used in this analysis, we did not find an association between the CMS and the incidence of dementia. One limitation to consider in our study is the short follow up period and the low prevalence of CMS opposite to other epidemiological studies that describe a prevalence of up to 7% with n = 997 (Verghese et al., 2013). We propose to explore new alternatives for the operationalization of this syndrome since the CMS has emerged as a robust short‐term predictor for the development of dementia.
The impact of hearing loss on cognitive decline and risk of progression to mild cognitive impairment in healthy adults
Authors: Bucholc Magda , McClean Paula , Bauermeister Sarah D. 
Published: December 2020

AbstractBackgroundHearing loss is the third most commonly reported chronic disease in older adults. Its prevalence ranges from 30% in individuals aged 65‐74 years to 40%‐60% in those aged 75 years or older. Evidence suggests that age‐related hearing impairment is strongly and independently associated with the decline in cognitive abilities and that individuals with hearing loss develop cognitive decline earlier than people with normal hearing. In this study, we used data from a large referral‐based cohort to investigate the effect of hearing impairment on cognitive decline and progression to mild cognitive impairment (MCI) in healthy adults.MethodThe longitudinal National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS), consisting of observations from the period 2005‐2018, was used to assess the impact of hearing loss on cognition and conversion to MCI in cognitively healthy individuals. The incidence of MCI was determined based on the clinical diagnosis. The analytic sample for this study included 691 participants (age >40) with hearing impairment. Kaplan‐Meier survival functions were used to estimate the distribution of survival times for patient subpopulations i.e. patients with and without hearing impairment. The survival duration was defined as the number of years between the baseline ‘healthy’ diagnosis and the first MCI diagnosis during the follow‐up. Cox proportional hazards regression model was developed to study time to incident MCI. Sensitivity analysis was performed to control for confounding.ResultPatients diagnosed with hearing impairment were at substantially higher risk of converting to MCI (hazard ratio [HR] 1.3; 95%CI, 1.07‐1.55; p = 0.008). Kaplan‐Meier analysis for the cumulative risk of MCI revealed large differences in survival rates by hearing impairment status (p = 0.0003). Sensitivity analysis confirmed the robustness of our findings. The results obtained after prosperity score matching again showed a significant association between hearing impairment and risk of conversion to MCI (HR 1.43; 95%CI, 1.14‐1.80; p = 0.002).ConclusionWe demonstrated the impact of hearing loss on cognition of healthy individuals. Future work will focus on evaluating the relationship between the use of hearing aids and conversion to MCI in hearing‐impaired healthy adults as well as investigating the mechanistic basis of this association.
Neuropsychological profile of language alterations in subcortical dementia of the white and gray matter
Authors: de Lacerda Maria Carolina Cabral , Caixeta Leonardo Ferreira 
Published: December 2020

AbstractBackgroundIn the twentieth century, it was believed that the injury cortical was the substrate of cerebral dysfunction neuropathological. Studies of dementia were primarily focused on disorders of the cerebral cortex and sub cortical gray region, which originated the concepts of cortical and subcortical dementia respectively. The report of dementia mainly involving the white brain received less attention.Method15 patients were evaluated with DSB, 8 with DSC and 14 control subjects. We applied the following tests: Boston for Diagnostic of Aphasia Examination (BDAE), the Boston Naming Test (BNT), Token Test, Verbal fluency ‐ semantic category and board Theft of biscuits.ResultThe results showed that the subcortical group showed worse performance with the control group, showing significant differences in the Boston Naming Test and on the evidence of comprehension and oral production and graphics for the Boston Diagnostic Test of Aphasia. The DSB group showed more significant changes when compared with the control group than in the comparison between DSC X control group. Despite the language is related to cortical involvement, our study showed that such changes are found in subcortical dementia and receiving influence of cognitive processes involved in language. Symptoms of changes in language were similar between groups subcortical, but in greater or lesser degree of commitment. The DSB group showed more impairment of comprehension and oral apraxia and DSC group is highlighted by changes in prosody and the presence of hyperkinetic dysarthria.ConclusionThe subcortical groups showed greater language impairment than the control group, formed by patients with cortical dementia and the domains most seriously involved were those of complex ideational understanding, oral and graphic speech, naming and apraxia, also another symptom present exclusively in this group.
Circulating extracellular vesicles as an emerging tool for the early detection of Alzheimer’s disease or other dementia
Authors: Khedher Mohamed Raâfet Ben , Haddad Mohamed , Laurin Danielle , Ramassamy Charles 
Published: December 2020

AbstractBackgroundAlzheimer disease (AD) and vascular dementia (VaD) are the most common form of dementia worldwide. Actually, the search for early peripheral biomarkers for AD and other dementia represent a great challenge. Exosomes or extracellular vesicles (EVs) are key players in cerebral function. We have demonstrated that the levels of some pathogenic proteins related to AD (amyloid, Tau..) were higher in circulating EVs (pEVs) than in plasma with a differential regulation in controls, mild cognitive impairment (MCI) and AD patients. However, it is not clear whether these changes are specific to AD or other dementia subtypes. Our prospective study aims to identify, in pEVs and in plasma, early specific biomarkers in pre‐clinical cognitively impaired non demented patients (CIND) that develop different types of dementia.MethodpEVs were isolated from plasma of healthy volunteers, AD patients and CIND patients stratified according to the type of dementia these patients develop five years after as follows: CIND, CIND‐AD, CIND‐VaD and CIND‐mixed dementia. EVs were characterized by NTA analysis, transmission electron microscopy and western‐blot measurement of vesicular proteins such as TSG101 and CD63. The selected brain‐specific proteins were assessed by Luminex assay.ResultOur results showed that pEVs display a better discriminating capacity than plasma for most of the studied proteins. DJ‐1 and NSE concentration in EVs were increased in CIND‐VaD patients but not in CIND‐AD suggesting their utility as early markers for VaD. The levels of ANGPTL‐4, lipocalin and α‐synuclein in pEVs were able to discriminate specifically the apparent‐stages of AD. The α‐synuclein/DJ‐1 ratio measured in pEVs was reduced in all groups and could not provide a fair classification of dementia subtypes. In addition, the levels of APP, MMP‐9, progranulin S100B and pentraxin‐2 were unchanged in pEVs and plasma.ConclusionThe present work show that several proteins contained in pEVs are differently expressed depending on the type of dementia and prompt the use of pEVs in early dementia diagnosis. This work was supported by the Chaire Louise & André on Alzheimer’s disease, Foundation Armand‐Frappier (CR) and CIHR grant (TF).
Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease
Authors: Gate David , Saligrama Naresha , Levanthal Olivia , Davis Mark , Wyss‐Coray Tony 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is an incurable neurodegenerative disorder in which neuroinflammation plays a critical function. Yet, little is known about the contribution of the adaptive immune response in AD. Here we used integrated analyses of multiple cohorts to identify peripheral and central adaptive immune changes in AD.MethodFirst, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of AD consisting of increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells.ResultIn a second cohort, we found that CD8+ TEMRA cells were negatively associated with cognition. Furthermore, single cell RNA sequencing revealed their enhanced T cell receptor (TCR) signaling. Notably, by utilizing multiple single cell TCR sequencing strategies on a third cohort, we discovered clonally expanded CD8+ TEMRA cells in patient cerebrospinal fluid (CSF). Finally, we used machine learning, cloning, and peptide screens to demonstrate specificity of clonally expanded AD CSF TCRs to two separate Epstein‐Barr virus antigens.ConclusionThese results reveal a novel blood‐CSF adaptive immune response in AD and provide evidence of clonal, antigen‐experienced T cells patrolling the intrathecal space of brains affected by age‐related neurodegeneration.
Relation between working into old age and MMSE: A study on older dressmakers in Japan
Authors: Sooudi Kazuyo K 
Published: December 2020

AbstractBackgroundThe number of older adults in Japan with dementia including MCI is estimated to increase to 13 million by 2025. The author’s earlier study indicated that a top concern among Japanese is dementia. The government also plans to increase the age to receive pension, which means older adults must work much longer. Purpose: To identify any benefits of working beyond retirement age from a dementia point of view.MethodsConducted the MMSE and one‐on‐one interviews with working seniors about their beliefs and life values (n=11). Analyzed interview contents using text mining tool. Ethical considerations: Ethics Committee of Nakamura Sewing Company approved research plan.ResultsFifty percent of subjects work full time (Av. Age: 73, 66‐80 YO. old, SD=4.1). All subjects achieved a perfect score on the MMSE, except on calculation (Av. score 2.6, 1‐5). Through text mining, top 4 words (word cloud) were “health, customer, satisfaction, responsibility” and top 3 words (word frequency) were “age, responsibility, equal.” All subjects walk to office (Av. 3km). Discussion: Although previous studies have stated that cognitive decline in memory starts in one’s late 30’s and reasoning/verbal ability in one’s 50’s, the subjects in this study did not show any obvious decline through the MMSE and the interview process. Most of them work as dressmakers an average of 30hours/w. This small study indicates that working into older age may contribute not only to financial security but also to delaying dementia. All subjects stated that they are very conscious not to use their age as an excuse for any error they make and expect to get equal remuneration for their work.ConclusionsActive lifestyle including working into the old age may be a way for older Japanese to maintain personal health (delaying and/or avoiding dementia) and also to sustain financial security.
Metabolic correlates of neuropsychological assessment in behavioral variant frontotemporal dementia
Authors: Matias‐Guiu Jordi A. , Cabrera‐Martín María Nieves , Delgado‐Álvarez Alfonso , Delgado‐Alonso Cristina , Valls‐Carbó Adrián , Moreno‐Ramos Teresa , Carreras José Luis , Pytel Vanesa , Matias‐Guiu Jorge 
Published: December 2020

AbstractBackgroundNeuropsychological assessment is an essential tool in the diagnosis and monitoring of patients with neurodegenerative disorders. Cognitive functions underlying neuropsychological tests are complex, and accordingly interpretation is often challenging. In behavioral variant frontotemporal dementia (bvFTD), neural correlates of cognitive testing are largely unknown, and they could be different to other settings such as Alzheimer’s disease (AD). In this study, we aimed to analyze the metabolic underpinnings of neuropsychological test results in a series of patients with bvFTD.MethodSeventy‐two patients with bv‐FTD according to the consensus criteria were included. Patients were examined with a comprehensive neuropsychological protocol and 18F‐FDG‐PET. Voxel‐based analysis was used to study the correlation between regional brain metabolism and cognitive performance of the following tests: Boston Naming Test (BNT), Trail Making Test (TMT), Rey‐Osterrieth Complex Figure, verbal fluency (semantic and phonological), Free and Cued Selective Reminding Test (FCSRT), Stroop Color Word Interference test, Tower of London, and Visual Object and Space Perception Battery (VOSP). Age, sex, and years of education were introduced as nuisance covariates. A healthy control and Alzheimer’s disease groups were also examined with the same protocol for comparison. Neuroimaging analyses were conducted using SPM12.ResultMean age in the bvFTD group was 71.33+/‐7.75 years, and 43 (59.7%) were men. In bvFTD, BNT was positively correlated with the left anterior temporal lobe; FCSRT was correlated with the left frontal cortex; Phonological fluency with left frontal lobe and right superior frontal; semantic fluency with left frontal, temporal and thalamus; TMT‐B was negatively correlated with bilateral medial frontal lobes, especially with the right side; VOSP was correlated with the right frontal lobe.ConclusionWe showed the brain regions associated to the performance of different standardized neuropsychological tests in bvFTD. The differences observed between bvFTD and AD suggests that neural underpinnings underlying these tests are different according to each disease, confirming the multiple cognitive processes involved during performance of each particular test. Overall, our study provides useful information to achieve a better understanding of neuropsychological examination in patients with bvFTD. In addition, these findings could be useful to detect cognitive subtypes within the syndrome of bvFTD.