bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delphi consensus on outcome measures for Alzheimer’s disease in clinical practice
Authors: Frisoni Giovanni B , Ellison Tim S , Cappa Stefano F , Georges Jean , Iwatsubo Takeshi , Lehmann Maryna , Lyketsos Constantine G. , Maier Andrea B. , Merrilees Jennifer , Morris John C , Naismith Sharon L , Nobili Flavio , Pahor Marco , Pond Dimity , Robinson Louise , Soysal Pinar , Vandenbulcke Mathieu , Weber Christopher J. , Visser Pieter Jelle , Weiner Michael W. 
Published: June 2023

AbstractBackgroundPrevious consensus initiatives on outcomes in Alzheimer’s disease (AD) have focused on clinical trials, may not be applicable to real‐world settings, and did not necessarily consider a comprehensive list or prioritize outcomes. The aim of this initiative was to achieve consensus among experts on priority outcomes and outcome measures for use in clinical practice when caring for patients with symptomatic AD.MethodThe Consensus Group consisted of 20 international voting members and a non‐voting Chair representing diverse specialities relevant to AD. A Delphi approach was used to generate shortlists of the most important outcomes and measures, and to develop consensus statements/recommendations (Figure 1). Initial lists of outcomes/measures were obtained from the ROADMAP project (roadmap‐alzheimer.org), and panel members were given the opportunity to suggest additional ones. The threshold for consensus was predefined as ≥70% voting “agree” or “strongly agree”. Shortlists of outcomes and measures were ranked by priority, their relative importance for mild and moderate disease was indicated, and assessment frequency was recommended. The modified GRADE criteria were used to rate the strength of recommendations and quality of evidence.ResultStrong consensus was readily reached on 37 statements/recommendations, grouped by ‘General Considerations’ (9) and nine domains (28) (Table 1), as well as on priority shortlists of outcomes and measures across the nine domains; an example of a priority shortlist for the domain ‘Cognitive abilities’ is shown in Table 2. The level of evidence for most items was low; therefore, most statements are based on panelists’ expert opinion. Key recommendations include: patient quality of life (QoL) outcome assessments should measure what the person performs well in addition to deficits, and take into account the values of patients and/or caregivers; there is a need for a more comprehensive measure to assess language and communication; ‘functional ability & dependency’ should include an assessment of motor function.ConclusionThis Delphi consensus highlights outcomes of highest importance in AD from a professional perspective and includes recommendations regarding the most appropriate measures for use in clinical practice. Further studies are needed to raise the strength of the recommendations and to explore patient/caregiver views.
Yesavage’s Geriatric Depression Questionnaire(GDS‐VE): Analysis of its internal structure inolder adults living in Buenos Aires, Argentina
Authors: Tartaglini María Florencia , Hermida Paula Daniela , Ofman Silvia Deborah , Feldberg Carolina , Heisecke Silvina Lidia , Somale Maria Veronica 
Published: June 2023

AbstractBackgroundDepression represents one of the most frequent and disabling mood disorders in the elderly population. To measure it, one of the most used scales is the Geriatric Depression Questionnaire, developed by Yesavage, in its abbreviated version (GDS‐VE). Despite its ample acknowledgment and frequent use, an analysis of these characteristics has not yet been carried out on the Argentine population. Currently, because of the COVID‐19 pandemic and the isolation context, the American Psychological Association recommends adapting face‐to‐face to virtual practices. Given this need, the present work aims to analyze the internal structure of the GDS‐VE, for pencil/paper and Internet modalities examining the metric equivalence between both of them.MethodA confirmatory factor analysis was carried out and the internal consistency was estimated for both modalities.ResultFactor invariance between both forms of administration was also examined. A total of 696 older adults participated and responded to the questionnaire, using two modes of administration (50% pencil‐paper and 50% Internet). As a result, an adequate adjustment of the model to the empirical data was verified for both versions (pencil‐paper and Internet), as well as an adequate metric invariance between them.ConclusionThese findings provide evidence of validity and reliability of the GDS‐VE instrument on the Argentine population.
The results of dementia care policy implementation in Eastern Taiwan
Authors: Tseng Wenting , Wang Naiyen , Lin Chiahui , Wang Chihong 
Published: June 2023

AbstractBackgroundHualien county locates in the eastern part of Taiwan is the biggest county but only 321,358 residents in Taiwan. There are 17.2% of the population over the age of 65, and the middle‐aged population migrated away for job‐seeking . Senile citizens’ health, especially dementia is a critical issue in this area.MethodMennonite Hospital Shoufeng Branch undertakes the Dementia Care Center Project of the Ministry of Health and Welfare, which sets up a one‐stop diagnostic and care service to people with dementia. Dementia Care Center provided caregivers with counseling for psychological support, home environmental improvement, problem solving skills for physical caring and behavioral and psychological symptoms of dementia. Case managers link and refer resources such as long‐term care resources, acute medical services, Day‐care center, psychiatric or neurological consultation from hospitals, NGO, or the government. In addition, we provide dementia awareness and health education for ordinary people, volunteers, polices, firefighters, teachers, and students in schools.Result1,245 people with dementia were enrolled, and according to CDR classification, Mild Cognitive Impairment (CDR = 0.5) accounted for 1%, mild(CDR = 1) 32%, moderate(CDR = 2) 43%, severe(CDR = 3) 17%.A total of 936 people with dementia were referred to care resources, the first five items of referral care and long‐term care resources are home services(23%), community care stations for dementia(18%), community health stations(11%), day care center (6%)and acute medical care(4%), and 88.3% were satisfied with family services. 6,590 people were educated in the community.ConclusionThe Dementia Care Center provides accessible care resources to help families with dementia in remote areas, the goal of aging in place of the dementia could be achieved.
Neuropathological correlates of neuropsychiatric symptoms in dementia
Authors: Gibson Lucy L , Grinberg Lea T. , Leite Renata Elaine Paraizo , Rodriguez Roberta Diehl , Ferretti‐Rebustini Renata Eloah de Lucena , Pasqualucci Carlos Augusto , Nitrini Ricardo , Jacob‐Filho Wilson , Aarsland Dag , Suemoto Claudia Kimie 
Published: June 2023

AbstractBackgroundNeuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia.MethodParticipants who passed away between 2004 and 2021 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies. Neuropathological data was collected for Lewy body neuropathology (LBD Braak score), neurofibrillary tangles (NFT Braak score), amyloid‐β burden (CERAD‐NP), TDP‐43, lacunar infarcts, cerebral amyloid angiopathy and hyaline atherosclerosis. Post‐mortem interviews were used to collect information regarding neuropsychiatric and cognitive status using the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR). A total of 948 cases were classified according to neuropathological assessment: (1) No pathology (NP) (n = 678); (2) Alzheimer’s Disease (AD) (n = 183); (3) LBD (n = 57); (4) AD+LBD (n = 30).ResultMultinomial logistic regression models comparing LBD, AD and AD+LBD to NP, adjusted for age, ethnicity, sex, and education level, showed significantly higher odds of hallucination and delusions across all groups compared to NP with the relative risk of hallucinations most elevated in AD+LBD cases (RRR = 19.3,[95%CI = 8.00‐46.3], p<0.001). All groups had increased risk of higher NPI scores relative to NP, but the greatest increase was for AD+LBD (RRR = 1.04, [95%CI = 1.02‐1.06], p<0.001). There were significantly greater risk of agitation and apathy in AD and AD+LBD groups relative to NP. (Table 1) Additionally, hallucinations were associated with higher Lewy body Braak scores (OR = 1.30, 95%CI = 1.13‐1.49, p<0.001). Higher NFT Braak scores were associated with depression (OR = 1.28, 95%CI = 1.09‐1.50, p<0.001), agitation (OR = 1.30, 95% CI = 1.07‐1.57, p = 0.009) and overall NPI score (IRR = 1.15, 95%CI = 1.05‐1.27, p = 0.004). Lacunar infarcts were associated with delusions (OR = 4.68, 95%CI = 1.12‐19.5, p = 0.03). More frequent neuritic plaques was inversely associated with apathy (OR = 0.70, 95%CI = 0.52‐0.93, p = 0.01). Cerebral amyloid angiopathy, hyaline atherosclerosis, and TDP‐43 did not associate with any of the neuropsychiatric symptoms in the multivariable logistic models. (Table 2)ConclusionLewy body pathology was the most significant contributor to the aetiology of hallucinations, while NFT were important contributors to depression and agitation in dementia. Supporting the dual importance of these pathologies, subjects with AD and LBD co‐pathology showed the greatest burden of NPS.
Differences in dynamic functional connectivity across the Alzheimer’s disease spectrum
Authors: Pfeil Julia , Hönig Merle C. , Drzezga Alexander , van Eimeren Thilo 
Published: June 2023

AbstractBackgroundTo examine differences in dynamic functional connectivity (DFC) in cognitively normal subjects (CN), and patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD).MethodResting‐state functional magnetic resonance imaging (rsfMRI data of 76 participants (40 CN, 24 MCI, 11 AD) from the ADNI database (http://adni.loni.usc.edu/) was used for analysis. Groups were matched according to age, sex and education. rsfMRI data were pre‐processed using the CONN toolbox. For data reduction purposes, spatial independent and principal component analyses were performed on the normalized rsfMRI using GIFT. Resulting meaningful independent components were clustered into 13 functional resting‐state networks. Using GIFT, a sliding window approach was employed to determine dynamic functional connectivity states across the scan period of 9 minutes. Afterwards, non‐parametric t‐tests were performed comparing the groups in measures of DFC such as dwell time (i.e. staying in a state), number of transitions (i.e. switching between states), fraction time (i.e. total time spent in a state), and meta state characteristics.ResultThe DFC analysis resulted in 4 distinct functional connectivity states, which were characterized by either global connectivity patterns or distinct connectivity patterns between certain rs‐networks. Group comparisons yielded that one state was particularly more occupied by the AD group compared to the CN group (p = .02) and the MCI group (p = .001). The AD group showed a lower meta state span and number of meta states compares to the MCI and CN groups.ConclusionNetwork reorganization may influence dynamic functional connectivity patterns in pre‐ and clinical AD.
FLAIR MRI biomarkers of the Normal‐Appearing Brain Matter (NABM) are related to APOE‐4 status and CSF markers Aβ42 and Tau
Authors: Chan Karissa , Fischer Corinne E. , Khosravani Houman , Black Sandra E. , Tyrrell Pascal , Maralani Pejman Jabehdar , Moody Alan R. , Khademi April 
Published: June 2023

AbstractBackgroundReduced amyloid‐beta‐42 (Aβ42) and elevated total tau (t‐tau) protein concentrations in the CSF are characteristic of Alzheimer’s disease (AD) pathology [1]. Aβ42 contributes to extracellular plaque formation between neurons [2]. The total level of tau, a microtubule‐stabilizer in neuron axons [3], is associated with neuronal death [1]. Additionally, presence of ApoE4 (ε4) alleles is an established identifier for increased risk of AD [4]. Non‐invasive imaging‐based correlates of the CSF markers are lacking. This study examines correlations of novel FLAIR texture, intensity, and volume biomarkers, along with white matter lesion (WML) burden, with Aβ42, t‐tau, and ε4 status.MethodFLAIR volumes (n = 4044) from the ADNI database were used for analysis with CSF biomarkers. A subset (n = 921) was used for ε4 analysis based on available data. Normal‐appearing brain matter (NABM) was obtained by removing CSF and WML. Macrostructural damage (MAD), microstructural damage (MID), and integrity (MII) texture biomarkers [5] were extracted from each NABM volume (Fig. 1), along with median intensity, NABM/ICV ratio, and normalized WML volume [5]. Relationships between FLAIR biomarkers and AD markers were described using parametric statistical analyses. Statistical significance was set at p<0.05.ResultAll FLAIR biomarkers were statistically significantly correlated with CSF Aβ42 levels. All features except MID and WML burden were significantly correlated with CSF t‐tau levels (Table 1). MAD, MID, and WML burden showed negative correlations with Aβ42, while MAD showed a positive correlation with t‐tau. Opposite trends were seen with MII, intensity, and NABM/ICV (Fig. 2). Significant differences between groups without and with one ε4 allele were found in all FLAIR biomarkers except WML burden. Significant differences in MAD, MII and NABM/ICV were found between groups with one and two ε4 alleles (Table 2).ConclusionFLAIR biomarkers were inversely associated with CSF Aβ42 concentrations, suggesting they may be surrogate markers of Aβ plaque formation. They were associated with CSF t‐tau concentrations, suggesting they could also be indicators of GM degeneration and neuronal death. They could also be indicators for patients at increased risk of AD, as they demonstrated significant differences with the presence of ε4. Further longitudinal studies are required to establish the exact mechanism of neurodegeneration.
Reliability, validity, and feasibility of a smartphone‐based cognitive assessment for preclinical Alzheimer disease
Authors: Nicosia Jessica , Aschenbrenner Andrew J. , Balota David A. , Sliwinski Martin J. , Tahan Marisol , Adams Sarah , Stout Sarah Holtz , Wilks Hannah M , Gordon Brian A. , Benzinger Tammie L.S. , Fagan Anne M. , Xiong Chengjie , Bateman Randall J. , Morris John C , Hassenstab Jason J. 
Published: June 2023

AbstractBackgroundSmartphone‐based ecological momentary assessments (EMA) have the potential to capture subtle changes in cognition associated with preclinical Alzheimer disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on EMA principles and administers brief tests of associative memory, processing speed, and working memory ∼4 times per day over 7 consecutive days. Participants perform these 7‐day cycles every ∼6 months, longitudinally. ARC was designed to be performed unsupervised, on participants’ personal devices, and in their everyday environments in order to increase accessibility, testing, and reliability.MethodWe evaluated the reliability, validity, and feasibility of ARC in a large, well‐characterized sample of cognitively normal older adults (ages 65‐97) and individuals with very mild dementia (ages 61‐88). Participants completed at least one 7‐day cycle of ARC testing along with conventional cognitive assessments. Most participants also had cerebrospinal fluid, amyloid and tau PET, and structural MRI data available. The reliability, validity, and feasibility of ARC as an unsupervised, high‐frequency cognitive assessment tool using participants’ personal smartphones was tested by examining (1) between‐subjects and test‐retest reliability, (2) correlations with age, conventional cognitive measures, and AD‐related biomarkers, and (3) adherence and attrition rates of older adults with varying technology familiarity.ResultFirst, ARC tasks demonstrated good reliability such that between‐person reliability across the 7‐day cycle and test‐retest reliabilities at 6‐month and 1‐year follow‐ups all exceeded intraclass correlations of 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures. Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, high adherence rates and low attrition rates indicated that ARC was feasible and, to some extent, enjoyable, for older adult participants.ConclusionUltimately, these results suggest that ARC is a reliable and valid measure of cognition in older adults at risk for AD and is a feasible tool for assessing subtle cognitive changes associated with the earliest stages of AD.
The relationship between emotion and cognition in cognitively healthy cohort: Using NIH toolbox emotion battery
Authors: Umucu Emre , Van Hulle Carol A. , Fischer Barbara L. , Wyman Mary F. , Lee Beatrice , Zuelsdorff Megan , Salazar Hector , Simó Carola A. Ferrer , Carlsson Cynthia M. , Johnson Sterling C. , Asthana Sanjay , Gleason Carey E. 
Published: June 2023

AbstractBackgroundThe NIH Toolbox was designed to provide brief, reliable, and valid measures of neurological and behavioral functions. Emotion assessment using the NIH Toolbox Emotion Battery has recently received significant attention given emerging evidence that emotional health is predictive of physical health and overall well‐being. The purpose of this study is to examine whether the modified emotion toolbox model is associated with cognition in sample of cognitively healthy adults.MethodParticipants were 529 enrollees in the Wisconsin ADRC who had normal cognition. The majority of participants were female (65.8%) and White (78.3%). Average age was 63.69 (SD = 8.37). NIH Toolbox Emotion Battery factors and a measure of executive function, Trail Making Test (TMT) Parts A & B were examined using SEM. To evaluate the overall goodness‐of‐fit, we used the following criteria: χ2 nonsignificant, χ2/df between1‐3, comparative fit index (CFI)>0.95, Tucker–Lewis index (TLI)>0.95, standardized root mean square residual (SRMR)<0.05, and the root mean square error of approximation (RMSEA)<0.08.ResultThe initial SEM results indicated a non‐acceptable fit for the data: χ2(51,N = 529) = 275.99, p<.01 (should be not significant), χ2/df = 5.41 (<3), CFI = 0.92(>.95), TLI = 0.90 (>.95), SRMR = 0.05, and RMSEA = 0.09 (<.08), 90% confidence interval (CI) = [0.08, 0.10] based on previously reported goodness‐of‐fit criteria. Based on modification indices, conceptually and statistically meaningful correlated error terms were added to the model (e,g., proximity between emotional support and friendship; emotional support and instrumental support; stress and sadness). After correlating some error terms based on theoretical background and modification indices, the modified SEM results indicated an acceptable fit for the data: χ2/df = 2.52 (<3), CFI = 0.98, TLI = 0.97, SRMR = 0.03 and RMSEA = 0.05, 90% confidence interval (CI) = [0.04,0.06].ConclusionOur modified model using the NIH Toolbox Emotion Battery had an acceptable fit for the data in a cognitively healthy cohort. Although we did not include all emotion toolbox variables, our modified model still had a great fit to the data. We specifically found that positive emotions including social satisfaction measures were correlated with cognition. We did not find any correlation between negative affect and cognition, which could be due to limited sample size. Measuring and identifying positive and negative emotions are important in clinical and research practice.
Amyloid on autopsy in the oldest‐old may be associated with sleep duration thirty years earlier: The 90+ Study
Authors: Melikyan Zarui A. , Mander Bryce A , Greenia Dana E. , Fletcher Evan M , Decarli Charles , Montine Thomas J. , Bukhari Syed A. , Paganini‐Hill Annlia , Kawas Claudia H. , Corrada María M. M. 
Published: June 2023

AbstractBackgroundAmyloid production and clearance from the brain are thought to be related to sleep duration. The association between brain amyloid accumulation and self‐reported sleep duration has been mostly established in cross‐sectional studies using PET. Our aim is to examine the longitudinal association between amyloid in the oldest‐old (90+ years), measured on autopsy and PET, with sleep duration self‐reported ∼30 years earlier.MethodWe analyzed data on 289 individuals with one‐time report of their usual nocturnal sleep duration as part of Leisure World Cohort Study (LWCS) in the early 1980s, and brain autopsy or 18F‐florbetapir (amyloid) PET between 2004 and 2021 with The 90+ Study. Sleep duration was analyzed as continuous and categorical variables (<7(short), 7‐8(optimal, reference) and >8 hours(long)). National Institute on Aging Alzheimer Association (NIA‐AA) amyloid (A) and neuritic (C) plaque scores were dichotomized as negative (0‐1, reference) and positive (2‐3). Standardized uptake value ratio (SUVr) for the posterior cingulate/precuneuswas analyzed as continuous and binary (SUVr <0.76 vs. ≥0.76) variables. We analyzed sleep duration, as predictor, in relation to amyloid on autopsy (A and C scores) and PET (SUVr), as outcomes, using multiple logistic and multiple linear regressions, controlling for age, sex, education, positive items from the Zung depression scale, and time between sleep report and PET or autopsy.ResultSleep was reported on average at 68 years, autopsy was done ∼29 years and PET was done ∼32 years later (Table 1). Long sleep, compared to optimal sleep, was associated with 67% decrease in the odds of being NIA‐AA A positive (Table 2). Although PET amyloid results were not significant, they suggest that every hour increase in sleep duration may be associated with 0.01 unit decrese in SUVr and with 11% lower odds of being PET amyloid positive (Table 3). PET amyloid by sleep group analysis was underpowered and not done.ConclusionIn this group of oldest‐old individuals, long, compared to optimal, sleep duration self‐reported 29 years earlier is associated with lower odds of amyloid deposition on autopsy. One of the plausible mechanisms is that longer sleep duration may support greater amyloid clearance and decreased production.