bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal neuroimaging correlates of NREM and REM sleep: EEG spectral power in aging
Authors: Andre Claire , Rehel Stéphane , Kuhn Elizabeth , Touron Edelweiss , Mézenge Florence , De la Sayette Vincent , Vivien Denis , Chetelat Gael , Rauchs Géraldine , Group Medit‐Ageing Research 
Published: December 2020

AbstractBackgroundSleep disturbances have been associated with cognitive decline and Alzheimer’s disease (AD), with growing efforts to understand how these changes may relate to AD pathophysiology. However, we lack a comprehensive overview of the associations between objectively‐measured sleep oscillations and brain changes in aging so that efficient treatment strategies could be developed. Using an unbiased, fast, and powerful quantitative (spectral) analysis of sleep EEG rhythms, we assessed the relationships between both non‐rapid eye movement (NREM) and REM sleep oscillations, and amyloid burden, gray matter (GM) volume and perfusion in cognitively unimpaired older adults (CUOA).Method125 CUOA from the Age‐Well randomized controlled trial underwent a neuropsychological assessment, an ambulatory polysomnography recording and a structural MRI. A Florbetapir‐PET scan was also performed with early and late acquisitions to measure brain perfusion and amyloid burden respectively. Normalized EEG spectral power values were obtained using the ASEEGA® algorithm for delta (0.1‐4 Hz), theta (4‐8 Hz), alpha (8‐12 Hz) and beta (16‐50 Hz) EEG frequency bands, over the Cz‐Pz derivation (Berthomier et al., 2007). Voxel‐wise multiple regressions were then conducted between EEG spectral power values and neuroimaging data (i.e., GM volume, perfusion and amyloid burden), separately for NREM and REM sleep, controlling for age, gender, education, the apnea‐hypopnea index, sleep medication use, and the ApoE4 status.ResultLower NREM sleep delta power, reflecting a decrease in slow wave activity, was related to decreased GM volume and perfusion in fronto‐cingulate areas, but not to amyloid deposition. By contrast, decreased REM sleep theta power was associated with i) greater amyloid deposition in frontal, cingulate, parietal and temporal areas; ii) lower GM volume in frontal, temporal, occipital and insular cortices, and iii) increased perfusion in frontal and parietal regions.ConclusionBoth NREM and REM sleep alterations were associated with structural and functional changes in regions sensitive to aging and AD pathophysiology. Importantly, REM sleep changes were associated with greater amyloid deposition. This may be due to early changes in cholinergic structures, acetylcholine playing a neuroprotective role against amyloid. Thus older individuals with REM sleep alterations may be more at risk of belonging to the Alzheimer’s continuum.
Using spatial filters to study regional reorganization of brain connectivity in familial early onset AD (PSEN1 E280A)
Authors: Quintero Carlos Andrés Tobón , Ochoa John F. , Aguillon David , García Francisco 
Published: December 2020

AbstractBackgroundThe most common cause of familial early onset Alzheimer Disease (AD) are the PSEN1 mutations. One of the largest family carriers of the mutation lives in Antioquia, Colombia. The study of mutation carriers provides a unique opportunity to characterize the preclinical changes and the brain reorganization strategies associated with predisposition to AD. The Electroencephalography (EEG) has an enormous potential to study the neurophysiological changes in neurodegenerative processes with promising clinical applications. During the 2012 – 2019 period different studies on a large database of high‐density EEG from PSEN1 E280A carriers were done trying to identify early changes that could be preclinical biomarkers of ADMethodA sample of 83 participants, belonging to families with genetic risk for AD by PSEN1 E280A mutation was included. They were distributed in three groups; asymptomatic carriers (AC, n=27), asymptomatic non‐carriers (ANC, n=33) and a symptomatic group with Mild Cognitive Impairment (SYMP, n=23). We used a 60 channel EEG for recording the brain electrical activity. The relative power values were obtained using Matlab’s chronux toolbox. The results obtained using a workflow based on Independent Component Analysis (ICA), introduced to improve the spatial resolution given by EEG, are discussed. A two‐parameter non‐parametric T‐test was used to calculate the statistical significance of the relative power among the populations analyzed.ResultThe comparison of carriers of PSEN1 E280A mutation and non‐carriers, show altered brain function even in asymptomatic stage complementing previous findings using functional Magnetic Resonance Imaging or Positron Emission Tomography. Regions, like the Precuneus, can be screened across the neurodegenerative process, offering new potential biomarkers of AD. The multivariate analysis of brain sources show generalized impairment in the brain connectivity for asymptomatic subjects. The results found using the workflow were compared with alternatives approaches of analysis, based on scalp EEG or data obtained through inverse solution methods, corroborating the findings.ConclusionThe neurophysiological correlates found opens the possibility of studying new biomarkers in AD based in EEG. The workflow proposed could be used in other neurodegenerative diseases or other brain mapping problems based in EEG.
Optimizing the unsupervised assessment of cognition in web‐based registries of individuals at risk for Alzheimer’s disease: Results from the Healthy Brain Project
Authors: Lim Yen Ying , Perin Stephanie , Buckley Rachel F. , Pase Matthew P. , Yassi Nawaf , Lavale Alexandra , Schembri Adrian , Maruff Paul T. 
Published: December 2020

AbstractBackgroundWeb‐based platforms are used increasingly to assess cognitive function in unsupervised settings. However, methods for ensuring the validity of cognitive data arising from unsupervised assessments are limited. We applied Human Computer Interaction (HCI) concepts of acceptability and usability to examine the validity of unsupervised cognitive testing in middle‐aged adults enrolled in the Healthy Brain Project (HBP).MethodA total of 1594 middle‐aged adults (mean age 56 years, SD 6.60 years) completed unsupervised assessments using a self‐administered version of the Cogstate Brief Battery (CBB) via our online platform, healthybrainproject.org.au. HCI acceptability was defined by the nature and amount of missing data, and HCI usability as (a) errors made during test performance, and (b) the time taken to read test instructions and complete the tests (learnability). We also explored whether cognitive performance varied across different testing environments (e.g., home/work alone, home/work with others around, public space).ResultOverall, we observed high acceptability (98% complete data) and high usability (95% met criteria for low error rates and high learnability). Test validity was confirmed by observation of expected inverse relationships between performance and increasing test difficulty and age. When accounting for the effects of age, no general influence of testing environment was found for any of the cognitive outcome measures in this study. Testing environment also had no significant effect on the proportion of individuals who satisfied our pre‐specified acceptability and usability criteria.ConclusionWith HCI acceptability and usability criteria considered, the data collected in this study retains similar psychometric characteristics to those collected from supervised testing of the same tests. The HCI definitions of acceptability and usability show great promise for use as real time algorithms for the collection of valid indices of cognition in unsupervised settings. This is of particular salience when considering the development of registries of individuals at risk for Alzheimer’s disease.
Dutch Brain Research Registry for online study participant recruitment: Design and first results
Authors: Zwan Marissa D , van Der Flier Wiesje , Cleutjens Solange , Vermunt Lisa , Jutten Roos J. , van Maurik Ingrid S , Sikkes Sietske AM , Weiner Michael W , Scheltens Philip , Prins Niels D 
Published: December 2020

AbstractBackgroundDifficulty in participant recruitment is a significant barrier to clinical dementia studies. The Dutch Brain Research Registry (www.hersenonderzoek.nl) was set up for online recruitment of participants for neuroscience studies in the Netherlands. Here we present first results with respect to participant registration and enrollment in studies. To evaluate this process, we investigated which demographic, social and health‐related factors were related to study participation.MethodRegistrants were primarily recruited through social media. The online registration process consists of a 10‐minute questionnaire including demographics, medical history, subjective memory complaints, medication and substance use. Registrants eligible for studies were selected based on provided data and invited by email. Those who accepted the invitation were contacted by the study investigator for further evaluation and enrollment. The relation of participant factors with study participation was analyzed using multivariate regression analyses.ResultIn the first eighteen months, 17.218 registrants signed up (58±11 years old, 78% female). Twenty‐eight studies have recruited participants via our platform, including 9 online observational studies, 14 onsite observational studies and 5 onsite intervention studies. Prescreening identified 34.696 eligible registrants, of whom 12.637 (36%) accepted the study invitation. After further evaluation by the study investigator, 10.661 registrants (31%) were successfully enrolled in studies. Compared to non‐participants, participants enrolled in studies were more often older (OR=1.32, CI=1.23‐1.40), male (OR=1.07, CI=1.00‐1.13), higher educated (OR=1.29, CI=1.22‐1.36), retired or not working (OR=1.14, CI=1.06‐1.21), non‐smoking (OR=1.59, CI=1.45‐1.73), reported a better health (OR=1.29, CI=1.18‐1.39) and had a 1st degree family member with dementia (OR=1.17, CI=1.11‐1.24).ConclusionThe Dutch Brain Research Registry facilitates effective matching of potential participants to brain research studies. Our findings demonstrate the feasibility to recruit participants via an online registry for a large number of studies with a high enrollment rate. In addition, participant factors related to study participation may reflect facilitators or barriers for study participation, as better self‐rated health and non‐smoking may express the participant’s interest in health‐related research. Furthermore, older age and a positive family history of dementia are associated with preclinical disease and therefore often used as prescreening for studies as well. These findings are useful for improving recruitment strategies.
Amyloid‐dependent association of grey matter network disruptions with phospho‐tau in preclinical Alzheimer’s disease
Authors: Lorenzini Luigi , Ingala Silvia , Wottschel Viktor , Wink Alle Meije , Mutsaerts Henri JMM , Haller Sven , Blennow Kaj , Schwarz Adam J. , Gispert Juan Domingo , Chetelat Gael , Waldman Adam , Visser Pieter Jelle , Tijms Betty M , Barkhof Frederik ,   the EPAD Consortium
Published: December 2020

AbstractBackgroundStructural Grey Matter Networks (GMN) show progressive disruptions in Alzheimer Disease (AD), starting from early, preclinical stages, and are related to amyloid aggregation. However, GMN associations with tau biomarkers remain unclear. Here, we investigated the relationship between GMN and phospho‐tau (p‐Tau) levels in CSF and whether this relationship was dependent on amyloid beta (Aβ), in a non‐demented population.MethodWe selected 423 individuals from the first data release of the European Prevention of Alzheimer Disease (EPAD, v500.0) that had MRI and CSF markers available; 84% were cognitively unimpaired (CDR=0) and 16% had CDR=0.5 (Table 1). Abnormal Aβ was defined by levels of <1025 pg/mL, and abnormal p‐Tau by levels of >24 pg/mL in the CSF. Single‐subject networks were extracted from 3D‐T1w structural MRI using a previously described method (Tijms BM et al., 2012), and for each individual we computed whole brain betweenness centrality, degree, density, clustering, modularity, path length and small world properties. Association of network metrics with Aβ and p‐Tau was investigated using linear models including Aβ, p‐Tau+ and Aβ‐p‐Tau interaction, both dichotomously (model 1) and continuously (model 2), adjusted for age, sex and Clinical Dementia Rating (CDR) scores.ResultsIn total 154 (36%) of individuals had Aβ+ (Table 1). Abnormal Aβ (both dichotomously and countinuously) was associated with lower degree, density, clustering and small‐world network properties, independently of tau (p<0.001). Higher p‐Tau levels were related to a reduction in clustering, modularity and small‐worldness values in the Aβ+ group only (p<0.05).ConclusionIn cognitively unimpaired subjects, grey matter networks show alterations in amyloid‐positive subjects, independently of tau, and within these individuals stronger GMN disruptions are related to higher p‐Tau levels. Our results indicate a relationship between molecular markers of AD and atrophy patterns at the single‐subject level, specifically going towards a more random and less clustered network topology, and suggest a possible role of GMN measures in identifying early stages of the pathology.
What patients want to know, and what we actually tell them: The ABIDE project
Authors: Fruijtier Agnetha D , Visser Leonie NC , Bouwman Femke , Lutz Rogier , Schoonenboom Niki SM , Kalisvaart Kees , Hempenius Liesbeth , Roks Gerwin , Boelaarts Leo , Claus Jules J , Kleijer Mariska , Beer Marlijn , van Der Flier Wiesje , Smets Ellen M 
Published: December 2020

AbstractIntroductionWe formerly identified 17 informational topics on which health care professionals, patients and care‐partners agree that these should be discussed during diagnostic consultations in memory clinics [1]. In addition, 8 topics were identified as highly relevant by at least one, but not all three groups. Here, we studied to what degree these 25 informational topics are actually discussed during diagnostic consultations and at whose initiative, i.e., the clinician, the patient or the care‐partner.MethodsAudio‐recordings of pre‐ and post‐test clinician‐patient consultations of 71 patients, seen by 32 clinicians (sample descriptives in table 1), were collected in eight memory clinics and independently content‐coded by two coders [2]. The coding scheme encompassed the 25 informational topics, grouped into 4 categories; (i) diagnostic testing, (ii) test results, (iii) diagnosis and prognosis, and (iv) practical implications.ResultsMany topics were discussed frequently, though individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of the patients. On average, 12 (SD=4) of the 25 topics were discussed per patient, during the diagnostic process. Topics in the category ‘diagnosis and prognosis’ were discussed least frequently (see figure 1). Patients and/or care‐partners rarely initiated discussion of a topic (topic initiated by clinician: 90%). When they did, the topic was most often one of the least frequently addressed topics (see figure 2), as well as one of the eight topics deemed highly relevant by at least one group (mostly patients and/or care‐partners), but not all three.ConclusionWe found most topics to be addressed quite frequently by clinicians in memory clinics, validating the feasibility of addressing these topics. Nevertheless, we observed considerable variation when looking at individual topics. Discussion of diagnostic or prognostic information was relatively limited, while patients and care‐partners consider this topic highly relevant, as substantiated by initiating discussion on diagnosis and/or prognosis. Hence, diagnostic or prognostic information should receive more attention in clinical practice. In addition, providing the topic list to patients prior to their visit could allow them to better prepare for the consultation and stimulate active participation.
Organizational, system, and policy level factors affecting dementia clinical research participation: Lessons from a pilot study
Authors: Bouranis Nicole , Gelmon Sherril B , Lindauer Allison , Waddell Elizabeth N , Richardson Dawn M , Woo Hyeyoung 
Published: December 2020

AbstractBackgroundFinding a dementia intervention is contingent on research participation. Current literature focuses on general factors affecting dementia clinical research participation, which do not speak to specific state or local factors nor the effects of local recruitment efforts. This study identified organizational, system, and policy level factors affecting local ADRD clinical research participation in Portland, Oregon.MethodA community advisory board (CAB) comprised of clinicians, researchers, advocates, people with dementia, family caregivers, and older African Americans was established for this project. Semi‐structured interviews were conducted with clinicians, advocates, and researchers. Interviews were audio‐recorded and coded; thematic analysis was used to allow themes to emerge from the data organically. The investigator was the single coder; the CAB then interpreted findings by identifying what was most important, surprising, or missing from the interviews.ResultNine clinicians, researchers, and advocates were interviewed. Interviewees were employed by or volunteered with health, research, and advocacy organizations of varying sizes and structures. Several findings emerged from the interviews. 1) Federal policy attempts to streamline research studies have not resulted in the intended outcomes at the local level. 2) People with ADRD and caregivers have a lack of awareness of research opportunities. In some cases, this was due to lack of provider knowledge; in others, it was due to organizational directives to not discuss or a provider’s personal preference. 3) Research opportunities are not shared in places where people with ADRD and their caregivers are likely to congregate. 4) Interviewees were often hesitant to join community collaborations or formal partnerships, and many were weary of including people with ADRD in their advisory boards.ConclusionIdentifying how these factors affect the decision of a person with ADRD to participate in local dementia clinical research is an important first step to increasing participation rates. Based on these factors, strategies can be developed and implemented to improve the ability and motivation of people with ADRD to join research studies in the Portland metropolitan area. This study should be replicated in other communities to determine contextual relevance and generalizability for other areas. Implemented strategies should be routinely evaluated to determine their feasibility and effectiveness.
Regional white matter hyperintensities predict Alzheimer’s‐like neurodegeneration
Authors: Rizvi Batool , Lao Patrick J , Chesebro Anthony G , Igwe Kay C , Amarante Erica , Beato Juliet M , Rivera Andres , Gutierrez Jose , Schupf Nicole , Zahodne Laura B , Manly Jennifer J , Mayeux Richard , Brickman Adam M 
Published: December 2020

AbstractBackgroundSmall vessel cerebrovascular disease, best visualized as white matter hyperintensities (WMH) on T2‐weighted MRI scanning, is associated with cognitive decline and increases risk for clinical Alzheimer’s disease (AD), particularly when it is distributed in posterior brain regions. There is much debate, however, about whether cerebrovascular disease represents a comorbidity or whether it is more fundamental to the pathogenesis of AD. The purpose of this study was to examine whether regional WMH volume predicts neurodegeneration, operationally‐defined as longitudinal decline in cortical thickness, among community‐dwelling older adults.MethodTwo hundred thirty‐eight participants(73.18+5.23 years old, 60% women, 35% APOE‐ε4 carriers, 30% non‐Hispanic White/32% Hispanic/38% Black, 14% with MCI) from the Washington Heights Inwood Columbia Aging Project (WHICAP) received high‐resolution structural 3T MRI scans at baseline and 4.09+1.57 years later. Regional WMH volume was derived with in house developed software and the FreeSurfer (v6.0) longitudinal processing stream was used to calculate change in cortical thickness. Using QDEC, we examined the relationship of total and regional WMH volume with annualized rate of decline in cortical thickness (symmetrized across the two visits) with vertex‐wise general linear models adjusted for age, sex, and APOE status. We additionally adjusted for a baseline marker of AD‐related atrophy (entorhinal cortex thickness).ResultBaseline total WMH volume predicted widespread cortical atrophy in a pattern consistent with AD‐associated atrophy, which included parahippocampal, temporal, and parietal regions. When examined regionally, the effects were most prominent for parietal lobe WMH, which predicted entorhinal cortex atrophy predominantly. Adjusting for baseline entorhinal cortical thickness did not alter the findings. In stratified analyses, the effects were strongest among Hispanic and Black participants compared with White participants, and similar across APOE groups.ConclusionWhite matter hyperintensity volume, especially in the parietal lobes, predicts Alzheimer’s‐like neurodegeneration, suggesting that small vessel cerebrovascular disease contributes to the ‘N’ aspect of the ‘A/T/N’ pathogenic models of AD. The results were independent of and stronger than baseline atrophy measures, suggesting that WMH are not simply a result of neurodegeneration. These effects may manifest differently across racial/ethnic groups, with small vessel cerebrovascular disease playing a more prominent role in future neurodegeneration among racial/ethnic minorities.