bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mayo‐PACC: Optimizing a parsimonious Preclinical Alzheimer’s disease cognitive composite comprised of public‐domain measures
Authors: Karstens Aimee J. , Twohy Erin L , Albertson Sabrina M. , Kremers Walter K. , Machulda Mary M. , Jack Clifford R. , Knopman David S. , Mielke Michelle M. , Petersen Ronald C. , Stricker Nikki H. 
Published: June 2023

AbstractBackgroundPreclinical Alzheimer’s cognitive composites (PACC) are designed to detect subtle cognitive changes in clinical trials. PACCs often include measures of memory, attention, and semantic fluency, with variations based on available measures. We created a Mayo Clinic PACC (Mayo‐PACC) to address limitations of existing PACCs by prioritizing parsimony, non‐proprietary measures, clinical applicability, and psychometric properties. We developed a Mayo‐PACC and examined sensitivity to detecting longitudinal cognitive change in amyloid positive (A+) older adults relative to the Preclinical Alzheimer’s Cognitive Composite‐Revised (PACC‐R). Exploratory analyses included comparison to other composites.MethodParticipants included 614 individuals in the Mayo Clinic Study of Aging (428 A‐ and 186 A+) age 65‐85 who were cognitively unimpaired at baseline with 7 years mean follow‐up. A+ was defined as PiB‐PET meta‐ROI SUVR ≥ 1.48 (centiloid 22). The Mayo‐PACC included the AVLT sum of trials (trials 1‐5, short delay, long delay), Trails B and Animal fluency. Measures included in the PACC‐R and other comparison composites are listed in Table 1. We calculated study‐specific z‐scores and examined psychometric properties of component measures including test‐retest reliability, practice effects, and distributional properties (ceiling/floor effects, skew, kurtosis). We examined sensitivity to preclinical cognitive change using slope estimates (difference in annualized change across A+ and A‐ groups) from linear mixed models (LMMs) for each composite. A jackknife procedure was used to calculate the standard error and subsequent confidence intervals of differences in rates of change (A+>A‐ indicating more significant decline in A+). Significance was determined based on whether the 95% Confidence Interval (CI) contained 0 (alpha = .05).ResultAll composites showed sensitivity to amyloid‐related longitudinal cognitive decline (A+>A‐ annualized change p<.05; see Table 2). Jack‐knife comparisons revealed comparable utility of Mayo‐PACC and PACC‐R (CI contained 0, see Table 3). Exploratory analyses revealed Mayo‐PACC performed similarly to an adaptation of the ADCS‐PACC, Global‐z, Memory‐z and Attention‐z. The Mayo‐PACC performed better than a 2‐measure Mayo‐PACC‐remote and a single memory measure.ConclusionThe Mayo‐PACC provides a parsimonious composite score that has comparable utility for detecting A+>A‐ cognitive decline compared to the PACC‐R and other composites and can be widely used in both research and clinical settings.
Comparison of word list recall and paragraph recall to distinguish dementia severity in the Uniform Data Set (UDS): Results from a diverse cohort
Authors: Loizos Maria , Zhu Carolyn W , Akrivos Jimmy , Sewell Margaret , Li Clara , Neugroschl Judith A. , Melnick Jonah , Grossman Hillel , Aloysi Amy , Schimming Corbett , Sano Mary 
Published: June 2023

AbstractBackgroundPrior research reported word list is more sensitive to changes early in the Alzheimer’s disease process. However, there is limited investigation into ethnic level differences between memory tests. This project examines: ethnic level (Black/African American) and testing language differences (Spanish) between word list and paragraph recall to distinguish dementia severity, and added benefit of using both tests.MethodBaseline UDS and site‐specific supplemental participant data collected at the Icahn School of Medicine at Mount Sinai’s Alzheimer’s Disease Research Center (ISMMS ADRC) were utilized to compare the efficacy of paragraph recall (Logical Memory and Craft Story) versus a word list test (CERAD) both together and alone in differentiating dementia severity as measured by the Clinical Dementia Rating (CDR) Scale. Composite scores for each memory test were established by calculating Z‐scores and taking the average. Logistic regression models were employed to distinguish between CDR 0 versus 0.5 and 0.5 versus 1. Receiver Operating Characteristic‐Area Under the Curves (ROC‐AUCs) were used as an indicator for overall performance in differentiating CDR. Subsample analyses were performed for White, Black/African American (AA), English, and Spanish language testing.Result1,319 participants who self‐identified as White (n = 788, 60%), Black/AA (n = 225, 17%), or Hispanic (n = 306, 23%). Results reveal high discriminability and no statistically significant difference between word list and paragraph recall in distinguishing between CDR 0 vs 0.5 (range AUC = 0.79 to 0.84; p>.05) or 0.5 vs 1 (range AUC = 0.81 to 0.87; p>.05). Discriminability was greater when combining tests in the overall group (0 vs 0.5 range AUC = 0.82 to 0.87; p<.01, 0.5 vs 1 range AUC = 0.81 to 0.93; p<.05) but this not always the case for the Black/AA group (0 vs 0.5 range AUC = 0.80 to 0.91; p>.05, 0.5 vs 1 range AUC = 0.83 to 0.93; p>.05) or Spanish speakers (0 vs 0.5 range AUC = 0.74 to 0.86; p>.05, 0.5 vs 1 range AUC = 0.85 to 0.90; p>.05).ConclusionOur findings confirm that there is utility in employing multiple memory tests to differentiate between CDR levels. However, these findings do not extend to all ethnically diverse or Spanish speaking participants. Researchers may want to consider burden of extra testing time when assessing the cognition of diverse participants.
A stakeholder‐engaged process to design and implement a dementia diagnosis Toolkit in primary care settings
Authors: Sideman Alissa Bernstein , Alagappan Cecilia , Segal‐Gidan Freddi , Alving Loren , Rosen Howard J. 
Published: June 2023

AbstractBackgroundDementia is frequently underdiagnosed or misdiagnosed in primary care, where most patients are initially seen. In 2018, in response to California State Bill 833, the ten California Alzheimer’s Disease Centers (CADCs) developed an instrument, the Assessment of Cognitive Complaints Toolkit for AD (ACCT‐AD), to guide primary care providers (PCPs) through the dementia diagnostic process. We examine how a stakeholder‐informed process shaped the development of the ACCT‐AD toolkit.MethodOur implementation study involved a two‐phase process. In Phase 1, experts from the CADCs provided consensus input to design the toolkit. We then conducted three focus groups with primary care providers to get feedback on toolkit design and workflow. Changes were made based on feedback. In Phase Two, we conducted 10 feedback sessions with providers who used or reviewed the toolkit and 124 surveys about experiences using the toolkit.ResultThe toolkit: The toolkit offers step‐by‐step instruction on how to collect information for a dementia diagnosis, including a series of questions, identified by CADC committee consensus. Each question is followed by examples of typical concerns. The toolkit interprets answers commonly encountered, indicating which are indicative of normal aging, Alzheimer’s disease (AD), or a non‐AD dementia. Focus groups: PCPs reported lack of systematic approach to diagnosing dementia and time constraints. They found the toolkit valuable as an educational tool but were concerned about length. They suggested modifications: a self‐administered questionnaire, streamline answer tracking, and electronic health record (EHR) integration. A major concern was how to identify patients who have Mild Cognitive Impairment (MCI). The team addressed all PCP concerns. Surveys, 66 providers found the toolkit extremely useful in identifying a probable diagnosis, 55 found it somewhat useful, 3 did not find it to be useful.ConclusionEngagement of stakeholders in the design and improvement of a dementia diagnosis toolkit is critical for improving its feasibility and usability for clinical practice. The ACCT‐AD toolkit is part of a larger vision to create a network of dementia‐proficient community practices connected to the CADC system. As potential treatments for AD and options for diagnostic testing evolve, this network can serve as a resource for disseminating knowledge.
Using electronic medical records to develop a predictive model of 30‐day hospital readmission for people with ADRD
Authors: Najarian Cyrus , Mahmoudi Elham , Wu Wenbo , Aikens James , Bynum Julie 
Published: June 2023

AbstractBackgroundHospitals are insufficiently equipped for Alzheimer’s disease and related dementia (ADRD) patients. Thus, readmission incidence is much higher and costlier among ADRD patients than the general population. Hospital discharges often occur without adequate preparation for the complex care management needs of ADRD patients and their caregivers. This study’s objective was to develop a risk‐assessment tool for hospitalized patients with ADRD. By supporting timely and better identification of who is at risk and why, already‐scarce resources can be allocated more efficiently to reduce readmissions.MethodsWe used 2016‐2019 EMR data from the University of Michigan health system (Michigan Medicine) and applied machine learning techniques (Random Forest, XGBoost, and Logistic LASSO) to develop a readmission risk‐assessment tool. We identified 2,899 individuals with ADRD who had at least one index hospital admission. All data features available in EMR – demographics, lab results, prior counts of healthcare use, and characteristics of index hospitalization – were included in our predictive models. Additionally, we geocoded the street address of place of residence using the National Neighborhood Data Archive (NaNDA) using the U.S. Census tract‐level information to include two composite measures of socioeconomic status: disadvantage and affluence.ResultsThe readmission rate for ADRD patients was 22% versus 17% for the general population. The best predictive model was the Random Forest (area under the receiver operating characteristic curve = 0.66; sensitivity = 0.64; specificity = 0.61). The accuracy of our model (0.61) was 42% higher than the LACE score (0.43), which is currently used by the hospital for all patients. The top 5 predictors of 30‐day readmission among people with ADRD included length of hospital stay, frailty index, living in a disadvantaged neighborhood, and total prior‐year healthcare charges.ConclusionADRD patients are highly vulnerable and require many resources, with substantially greater readmission risk and elevated rates of other adverse health events. Leveraging EMR data in a readmission risk‐assessment tool can help inform appropriate and efficient coordination and transitions of care for ADRD patients. Our risk‐assessment tool can identify ADRD patients at high risk for readmission and why they are at higher risk. This can enable better decision‐making upon discharge.
Lower extremity kinematic comparisons between patients with mild cognitive impairment and healthy individuals during single and dual tasks
Authors: Kuan Yi‐Chun ,   Dementia
Published: June 2023

AbstractBackgroundMild cognitive impairment (MCI) is one of the common health issues in modern societies, and it has a high rate of progression to dementia. Studies have shown that MCI has the potential to cause abnormal postural control and altered intersegmental coordination during functional activities, which may be one of the causes that lead to the increase of the risk of falls. The study aimed to compare the kinematics of the lower limb joints between patients with MCI and healthy controls during single‐task (gait) and cognitive or motor dual‐tasks (gait with arithmetic subtraction or tray handling).MethodSeventeen patients with MCI (age: 67.6±3.9 yrs; BMI:23.5±3.7) and seventeen healthy individuals (age: 67.9±3.7 yrs; BMI:24.0±4.2) were recruited in the study. Each participant performed single‐task (gait), cognitive dual tasks (gait while conducting arithmetic subtraction), and motor dual tasks (gait while balancing a ball on a tray), and the movements were recorded by a standard motion capture system. Peak angular magnitudes of the hip, knee, and ankle in the sagittal plane were extracted. Differences between the MCI and control groups were defined by independent t‐tests with a significant level at 0.05.ResultsThe significant differences between groups were found at the hip joint but not at the knee and ankle joint in all single‐ and dual‐tasks conditions. Compared to the healthy group, the MCI group demonstrated less maximum hip flexion and greater hip extension during the stance phase and less maximum hip flexion during the swing phase. The hip kinematics difference might be a change of the control of hip and pelvis muscles due to MCI thus altering the hip kinematic performance. This may also explain the increasing fall risks in patients with MCI due to this altered hip control strategy.ConclusionIn summary, the patients with MCI may have an alternative hip kinematic adaptation that is different from the healthy individuals. However, the cause of this adaptation is not clear at this point, and further investigation is necessary to make sure whether this is an important biomechanical marker or not.
Evaluation of cognitive performance and daily life activities in dementia patients with online cognitive tracking and exercise application
Authors: Bülbül Nazlı Gamze , Çınar Nilgün , Özge Aynur , Saka Esen , Oktar Ayla Çulha , Er Didem , Küspeci Özge Yılmaz , Okluoğlu Tuğba , Doğan Hasan , Evlice Ahmet Turan , Demirel Esra Acıman , Mungan Behiye , Adapınar Demet Özbabalık , Gelişin Özlem , Kibaroğlu Seda , Can Ufuk , Kenangil Gülay , Kandemir Arzu Uluakay , Yılmaz Gülcan Göçmen , Kiraz Mümine Özdağ , Taşkıran Aslıhan , Çakmaklı Gül Yalçın , Özer Özge Gönül , Sakallı Nazan , İşeri Pervin Kutluay , İnci İpek , Susuz Çiğdem , Bölükbaşı Okan , Akkaya Ömer Faruk , Gürsoy Görkem Tutal , Bizpınar Özlem , Ülker Mustafa , Şirinocak Pınar , Öz Didem , Mehdiyev Duygu , Çelik Çiğdem , Genç Hamit , Kutlar Hamdiye Nihal , Sarı Tacim , Menengiç Kübra Nur , KARALI Fenise Selin , Ateş Miruna Florentina , Şahiner Türker AH 
Published: June 2023

AbstractBackgroundBEYNEX (version 2.0) is an online application for tracking cognitive abilities using gamified follow‐up tests designed in eight different cognitive categories by Neurologists and psychologists. In this study, we aimed to determine and monitor the cognitive level of the person using this application by establishing an early alarm system, and to evaluate their relationship with daily living activities.MethodOur study was designed as multicenter and prospective. Free codes were given to the patients to enter the BEYNEX 2.0 application. The initial cognitive evaluations of the patients who entered the application using the codes were recorded by measuring with the online SLUMS (The Saint Louis Mental Status Examination Test), and a questionnaire was presented to evaluate the activity of their life at least once every seven days.Result265 patients aged between 58 and 75 years participated in the study. There was an increase especially in attention, language and memory scores, as the SLUMS score increased in patients with a SLUMS score above 17 (p = 0.001). No significant change was observed in speed and flexibility scores (p = 0.001). There was an increase in problem solving, memory and arithmetic scores of people with an SLUMS score below 17 as SLUMS increased (p = 0.001), but no change was observed in flexibility and language scores (p = 0.001). As the SLUMS score increases, the sleep quality of the patients, the time they spend on hobbies and social media increase in direct proportion.ConclusionOnline tracking and exercise applications may act as an early warning system in terms of providing feedback to caregivers in terms of monitoring cognitive functions and allowing patients to follow themselves at an early stage, and also monitoring the ADLs of dementia patients and observing their changes over time is as important as the medical treatment given to the patient.
Neural mass framework for decoding amyloid and Tau impact on neuronal activity under Alzheimer’s Disease
Authors: Sanchez‐Rodriguez Lazaro M , Medina Yasser Iturria 
Published: June 2023

AbstractBackgroundWe introduce a computational brain network model to understand the effect of abnormal microscopical processes into non‐invasive macroscopic neuronal activity observations and cognitive impairment across the Alzheimer’s disease (AD) spectrum. Amyloid‐beta (Aβ) plaques and tau protein aggregates (τ) modulate neuronal firing with the former likely increasing firing (hyperactivity) and the latter inhibiting activity (hypoactivity), especially in the abundant pyramidal populations ‐see (Maestu et al., 2021) for more details. We assume that such interactions scale up to macroscopic regions in humans, specifically influencing resting‐state fMRI signals.MethodMultimodal data, including amyloid ([18F]Florbetapir) and tau ([18F]flortaucipir) PET, baseline resting‐state fMRI, structural and diffusion MRI, and clinical/cognitive indicators were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The imaging modalities were processed to produce values for a parcellation consisting of 66 brain regions. We considered four neural masses interacting within a region. The regional excitatory and inhibitory activities then transform into BOLD signals (Valdes‐Sosa et al., 2009) ‐see Fig. 1A. Pyramidal excitabilities (v0E,k) contain the Aβ‐ and τ‐ parameters of interest, and their combined effect (Fig. 1B), which we estimated by minimizing the spectral distance between simulated signals and observations.ResultThe synergy between disease factors seems to change with disease states and subjects (Fig. 1C). Most of the considered healthy controls (HC) presented relatively low excitability change by Aβ and by τ, albeit having a greater, generally positive or ‘towards hypoactivity’ combined action. Mild cognitive impairment subjects appeared in two sub‐groups, one significantly close to the HC and another with stronger individual effects and smaller joined action. All AD patients presented positive synergistic effects and relatively high independent contributions to pyramidal population firing, as estimated from the data.ConclusionThe obtained significant, subject‐specific influences of pathological factors on neural activity verify the interactions reported by (Busche et al., 2020) in animal models experiments at the mesoscopic scale. There exist causal relationships between the amyloid and tau influence parameters and clinical variables. Further research must be performed to clarify characteristic disease trajectories as effective sub‐typing in early stages could improve therapeutic interventions.
Impact of the COVID‐19 pandemic on early career dementia researchers: a global online survey
Authors: Shaaban C. Elizabeth , Bartels Sara , Brum Wagner S. , Welikovitch Lindsay A. , Folarin Royhaan , Smith Adam ,   ISTAART PEERs PIA
Published: June 2023

AbstractBackgroundThe COVID‐19 pandemic has strained research around the world and has presented an unprecedented challenge to early career researchers (ECRs). The ISTAART Professional Interest Area (PIA) to Elevate Early Career Researchers (PEERs) works with worldwide dementia ECRs to attract, support, and retain them in dementia research. A key aim is to understand, bring attention to, and develop solutions for career challenges faced by ECRs. Our study objective was to understand the impacts of the pandemic on dementia ECRs.MethodsWe queried ECRs’ pandemic experiences in a global online survey conducted from September 1, 2021, through October 31, 2021. The survey was shared through ISTAART membership emails and newsletters, social media, podcasts, discussion boards, and emailing lists. Participation was open to individuals who self‐identified as ECRs (students through early career/pre‐tenure faculty) presently working in any dementia‐related research discipline or who left dementia research within the prior two years. Data were analyzed using descriptive statistics.ResultsECRs from 34 countries responded to the survey (n = 321; 68% women; 79% working in academia). Overall, 78% indicated experiencing research delays; 54% had to make project adjustments; 41% reported a negative impact on their career progression due to lack of funding or job opportunities; and 38% required additional or extended funding. Furthermore, 43% thought institutions/employers could have supported them better, and 20% felt their institutions/employers did not support them at all. We also noted 31% of respondents reported increased conference attendance during the pandemic.ConclusionWe recommend: 1) funders and institutions provide additional sources of funding, both specific to ECRs and on which ECRs may be co‐applicants; 2) principal investigators/supervisors and institutions support opportunities for ECRs to have enhanced research community participation online, such as networking, presenting their work in webinars, and online or hybrid conference attendance; 3) professional organizations maintain hybrid conference options in the future, given the expanded and more affordable access they give ECRs, especially those from low‐ and middle‐income countries; and 4) institutions and supervisors adjust promotion and tenure review requirements to accommodate inabilities to work in the same way during the pandemic. We also highlight resources specific to dementia ECRs.
A new synthesis of aberrant reward processing in frontotemporal dementias
Authors: Chokesuwattanaskul Anthipa , Jiang Harmony , Bond Rebecca L , van Leeuwen Janneke EP , Sivasathiaseelan Harri , Hardy Chris , Rohrer Jonathan D. , Warren Jason D 
Published: June 2023

AbstractBackgroundAberrant reward processing is a cardinal feature of frontotemporal dementias (FTD), driving abnormal socio‐emotional behaviours that define these diseases clinically. However, the hedonic architecture of FTD remains poorly characterised. Here we addressed this issue for a multimodal spectrum of hedonic behaviours in a large patient cohort representing all major syndromes of FTD.MethodTwenty‐seven patients with behavioural variant (bv)FTD and 58 with primary progressive aphasia (PPA) (24 non‐fluent variant (nfvPPA), 22 semantic (svPPA), 12 logopenic (lvPPA)) were studied in relation to 34 patients with typical Alzheimer’s disease (AD) and 42 healthy controls. Patients’ caregivers completed a questionnaire recording changes in liking and/or interest in stimuli or activities with primary (appetite/sweet tooth, sex) or non‐primary (music, religion, art, colour) reward value. We applied multiple correspondence analysis (MCA) to map the relationships between hedonic domains and extract core factors defining aberrant hedonic phenotypes. Voxel‐based morphometry (VBM) was used to define neuroanatomical substrates across the patient cohort.ResultThe most striking hedonic phenotypes defined bvFTD and svPPA: whereas both syndromes were characterised by altered hedonic valuation of food, they were polarised by their profiles in other hedonic domains (bvFTD ‐ decreased interest in sex and music, altered interest in art and colour; svPPA ‐ increased interest in sex, religion and music). Across the combined participant cohort, one MCA factor largely accounted for the presence of hedonic alterations: this factor was linked to a diverse repertoire of appetitive and socio‐emotional behaviours (apathy, disinhibition, inappropriate humour and affection) and underpinned by grey matter loss in a distributed frontotemporal and subcortical network anchored in right anterior temporal cortex. A second MCA factor largely determined the polarity of altered hedonic valuation (approach vs avoidance).ConclusionOur findings define new, multimodal hedonic phenotypes of bvFTD and svPPA and suggest a neurobiological synthesis in which involvement of right anterior temporal lobe and its connections drives the phenotypic expression of aberrant reward processing across the FTD and AD spectrum. This work has implications for the development of novel hedonic instruments and biomarkers in neurodegenerative diseases.