bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective and risk factors of cognitive decline and dementia with a special emphasis on social health: A systematic mapping review
Authors: Lenart Marta , Luc Mateusz , Pawlowski Marcin , Seifert Imke , Wiegelmann Henrik , Szczesniak Dorota , Gerhardus Ansgar , Wolf‐Ostermann Karin , Rouwette Etienne , Rymaszewska Joanna 
Published: December 2020

AbstractBackgroundInsufficient knowledge about dementia and factors influencing its course account for the scarcity of effective interventions and thereby, spiralling social costs related to care for an increasing population of people with dementia. This systematic mapping review is a part of JPND project Social Health And Reserve in the Dementia patient journey (SHARED), aimed to comprehensively map existing evidence on factors impacting cognitive functions and the development and course of dementia, along with a special emphasis on the social health.MethodThis review followed PRISMA Checklist. Medline, PsycINFO, CINAHL Complete, Cochrane Database and Epistemonikos were searched for systematic reviews and meta‐analyses from 2009 to 2019. Reviewers independently screened, reviewed and assessed methodological quality of articles.ResultAmong the 314 included studies, factors affecting cognitive functions and the development of dementia were recorded 586 times under 7 categories: personal (22), socioeconomic (33), lifestyle (143), psychological (53), environmental (25), neurobiological (278) and social health (32). Among these records, risk factors were the most frequently reported (350 times), while protective factors were mainly detected in the lifestyle (58) and social health (15) categories. In addition, the type of impact was unclear for 84 reported mentions.ConclusionThe results indicate the dominance of research on neurobiological (47.4%) over social health (5.5%) evidence, as well as on risk (59.7%) over protective (14.8%) factors. Obtained data show the potential of studies on social health in the context of dementia prevention and the need for further research on lesser known factors positively influencing cognitive functions.
Challenges in the development of accurate normative neuropsychological test data for older adults: Findings from the HELIAD Study
Authors: Arampatzi Xanthi , Margioti Eleni , Yannakoulia Mary , Hadjigeorgiou Georgios M. , Dardiotis Efthimios , Sakka Paraskevi , Scarmeas Nikolaos , Kosmidis Mary 
Published: December 2020

AbstractBackgroundNormative data collected from older adult cohorts may be tainted by the inadvertent inclusion of undiagnosed individuals at the very early stage of a dementia process or Mild Cognitive Impairment (MCI). To avoid this pitfall, we developed normative data from an older adult group who remained cognitively intact at follow‐up examination. The present work addresses the challenge and the absence of appropriate normative data for a range of neuropsychological tests in older adults in Greece.Method1031 community dwelling participants (age≥65) underwent neurological and neuropsychological assessment on two occasions with a mean interval of 2.8 years (range:1.2‐5.2; SD:0.8) for the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A value of 0 or 0.5 for the Clinical Dementia Rating (CDR) and a threshold value of ≥ 26 on the Mini Mental State Examination (MMSE) were used as clinical diagnostic criteria to determine the cognitive status of the participants. Based on these criteria, 750 individuals were cognitively intact in both evaluations and their data were used for norms development. Participants received a comprehensive neuropsychological assessment encompassing five cognitive domains: memory, language, attention/speed, executive and visual‐spatial functioning. Multiple linear regression models were performed, with age at baseline (years), education (years) and sex as the demographic predictors for regression‐based normative formulae, and raw test scores as the dependent variables. The effects of age, education and sex were investigated for each test and subtest separately. Discrete norms were also derived, stratified by four age strata (64‐69, 70‐74, 75‐79, 80‐89) and by three education strata (0, 1‐9, 10+).ResultRegression analyses revealed that education was associated with all test scores, whereas age was an important predictor of all but a few visuoperceptual, executive functioning and memory variables. Women outperformed men on verbal memory, attention/information processing speed and subtests of executive functioning. Men, however, outperformed women on visual memory recall and visuospatial perception.ConclusionThe current study provides sound normative data for widely‐used neuropsychological tests among older adults, untainted by potential early and undiagnosed cognitive impairment. We report both discrete and regression‐based norms for use in clinical settings to identify cognitive decline in older adults.
Neuroanatomical signature of super‐ageing: Structural brain study of youthful episodic memory in people over the age of 80
Authors: Pascual Marta Garo , Zhang Linda , Defelipe Javier , Gaser Christian , Medina Miguel , Strange Bryan A 
Published: December 2020

AbstractBackgroundSuperagers are people over the age of 80 that possess an episodic memory function of a person 20‐30 years younger. By drawing on a large (N=1213) longitudinal cohort of elderly individuals, we aimed to identify a superager subgroup and to determine key differences, including brain structure, between superagers and peers with normal episodic memory for their age.MethodA sample of 64 superagers (mean age 81.9 years, 59.4% women) and 19 age‐matched controls (mean age 82.6 years, 57.9% women) from the Vallecas Project cohort based at Fundación CIEN were selected according to their episodic memory score in the Free and Cued Selective Reminding Test; superagers scored at or above the mean value of a 50‐56yo person and controls scored within one standard deviation for their age. Demographic, genetic (APOE), lifestyle, clinical and neuropsychological variables were compared. Structural whole‐brain measures of grey matter volume are analised across groups at baseline and over time for up to 5 years (2‐6 time points) using CAT12 toolbox in SPM12.ResultThere were no differences in age, sex, years of education, current frequency of physical exercise or APOE genotype across groups. A history of anxiety, depression and cardiopathy was less frequent in superagers. At baseline, a higher grey matter volume in superagers compared to controls was shown in the bilateral anterior thalamus and regions within the temporal lobe including bilateral effects in the hippocampus, the amygdala, the entorhinal cortex, the parahippocampal gyrus and the fusiform gyrus (p < 0.05 FWE corrected). The longitudinal analysis revealed reduced grey matter volume loss over time in superagers in bilateral hippocampus, entorhinal cortex, parahippocampal gyrus, the left amygdala, bilateral basal forebrain, caudate, anterior insula, and right posterior cingulate (p < 0.05 FWE corrected).ConclusionBaseline differences between these two populations were located in a neuroanatomical network linked with memory function including key areas within the temporal lobe and also the anterior thalamus. The atrophy rate over time in these temporal regions is slower for the superager group, suggesting that they are more resistant than controls to the ageing decline of memory‐related areas.
Race or ethnicity is a factor that should be considered for establishing the normative data of subcortical brain volumes in normal aging
Authors: Choi Yu Yong , Kim Hoowon , Lee Kun Ho 
Published: December 2020

AbstractBackgroundThe norms of aging brain are important to diagnose degenerative brain diseases. However existing analyses have mainly focused on Caucasian samples. Particularly, the aging brain of East Asians has not been fully studied. The study aimed to investigate ethnic differences in aging process of regional brain volumes, specifically to determine to what extent ethnicity affects the normative volumes of subcortical brain structures in normal elderly people.MethodWe measured subcortical volumes from brain magnetic resonance (MR) images of 1,686 cognitively normal elderly Koreans aged 59 to 89 using FreeSurfer. For Caucasians, the brain images of 855 Caucasian‐Non‐Hispanic subjects were selected from the ADNI and OASIS datasets. The regression model predicting brain volumes were built using ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and scanner manufacturers as predictors. Based on the prediction model, the z‐scores of each individual were calculated. To validate the z‐score for diagnosis, 420 Alzheimer’s disease (AD) subjects of Koreans and Caucasians, and the same number of normal subjects were selected. The four validation groups divided by race and diagnosis were age‐ and sex‐matched using a propensity score matching method.ResultThe models predicting subcortical volumes had a considerate amount of explained variance (mean R2: 31.8%, range: 12.7%–45.5%). Ethnicity explained substantial variances for thalamus, accumbens, and hippocampus (for all subcortical volumes, mean R2: 3.5%, range: 0.1%–11.6%), comparable to age (mean R2: 4.0%, range: 0.0%–12.2%).ConclusionRace or ethnicity should be considered for establishing the normative data of subcortical brain volumes in normal aging. Otherwise, it can mislead clinicians into making an incorrect diagnosis.
Loneliness and isolation among people with dementia and their carers: Prevalence, risk factors and a dyadic analysis
Authors: Rippon Isla , Victor Christina R , Quinn Catherine , Martyr Anthony , Matthews Fiona E , Clare Linda 
Published: December 2020

AbstractBackgroundPeople with dementia and their carers may be vulnerable to loneliness and isolation. We investigated: (a) prevalence of, and risk factors for, loneliness and isolation among people with dementia and their carers and (b) the interrelationship between loneliness and isolation for dyads (person with dementia and carer).MethodThe IDEAL cohort of people with dementia and their carers includes two loneliness measures: the 6 item de Jong Gierveld (DJG) scale (range 0‐6 and classified: not lonely (0‐2), moderately lonely (3‐4) and severely lonely (5+)) and a single‐item question, plus a measure of social isolation, the six‐item Lubben social network scale (range 0‐30: not isolated (13+) or isolated (12 or less). For dyads consisting of a carer and a person with dementia, 1089 had complete data on loneliness and 1204 on social isolation. We report prevalence and examine loneliness/isolation risk factors using regression analysis for people with dementia and carers separately. We use Actor‐Partner Interdependence Models (APIM) to examine the relationship between isolation and loneliness within dyads and vice‐versa.ResultPrevalence of severe loneliness for people with dementia was 10% (single item score) and 5% (DJG score 5+) (15% and 18% respectively for carers). One third of people with dementia, 35%, were at risk of isolation (18% of carers). Social isolation was the only risk factor for loneliness consistent for both carers and people with dementia. Risk factors for loneliness in carers were caregiving stress and relationship quality and in people with dementia living alone, depression and life satisfaction/quality of life. Loneliness ratings were congruent in 43.1% of dyads (67.8% for isolation). Dyadic analysis using APIM demonstrates that loneliness is affected by both individuals’ own isolation and that of their partners.There were also actor and partner effects for the association between loneliness and isolation.ConclusionMost people with dementia and their carers are neither lonely nor isolated. Risk factors for loneliness are different for carers and people with dementia. Isolation in the carers influences the loneliness of the person with dementia and vice versa.
Czech National Action Plan for Alzheimer’s Disease and Related Illnesses 2020–2030: First implementation steps
Authors: Broulíková Hana M. 
Published: December 2020

AbstractBackgroundIn 2019, Czechia developed a National Action Plan for Alzheimer’s Disease and Related Illnesses (Plan), which will be implemented during the period 2020–2030. The Plan comprises three parts: a vision, a situational analysis, and proposed recommendations. The proposed recommendations consist of almost fifty activities organized around six strategic aims. Unlike its unsuccessful predecessor for the years 2016–2019, the Plan devotes its very first strategic aim to actions concerning development, monitoring and evaluation of the whole implementation process. These include for instance appointing a national dementia coordinator and an advisory stakeholder committee. The substantive strategic aims of the Plan are: 1) national interdisciplinary guidelines and a stronger network of services, 2) education, 3) dementia awareness and prevention, 4) epidemiology and research, and 5) legal protection.MethodThe goal of this conference contribution is to assess continuity between the development and implementation phase of the Plan by evaluating the completion of activities associated with the procedural strategic aim as well as initiated implementation of all other activities. This assessment is based on tools issued by the World Health Organization including Towards a Dementia Plan: A WHO Guide (World Health Organization, 2018). This guide is intended to assist countries in adapting their health and social care systems in order to accommodate the needs of people with dementia.ResultAs of January 2020, the position of the national dementia coordinator was anchored within the Ministry of Health. The works on an implementation roadmap and a first evaluation conference have been initiated. However, neither the coordinator nor the stakeholder advisory committee have been appointed yet. On the other hand, projects implementing some of the recommended activities such as interdisciplinary guidelines are already in the preparation phase.ConclusionThe Czech National Action Plan for Alzheimer’s Disease and Related Illnesses has transited to its implementation phase.
Is dysregulation of cerebral perfusion an early marker and cause of MCI and AD?
Authors: Marmarelis Vasilis , Shin Dae , Zhang Rong 
Published: December 2020

AbstractBackgroundOur previous work has shown that the dynamic vasomotor CO2 reactivity of cerebral vasculature is significantly reduced (p<0.01) in amnestic MCI patients relative to age‐matched controls [Marmarelis et al., J. Alzh. Dis. 56:89–105, 2017]. This quantitative result was obtained through dynamic modeling of the effects of spontaneous changes of arterial blood pressure (ABP) and end‐tidal CO2 (etCO2) upon cerebral blood flow or cortical tissue oxygenation (CTO) measured via Near‐Infrared Spectroscopy at the lateral prefrontal cortex. This study incorporated the dynamic effects of additional contemporaneous changes of heart‐rate (HR), respiratory‐rate (RR) and tidal‐volume (TV) to examine whether and how the intertwined dynamics of these complex mechanisms of physiological regulation influence differentially the cerebral/cortical perfusion in MCI patients versus age‐matched controls.MethodWe employed our novel multi‐variate predictive modeling methodology to quantify the input‐output dynamic relationship between contemporaneous changes of CTO (output) and five input variables: ABP, etCO2, HR, RR and TV, under spontaneous resting conditions. The obtained subject‐specific input‐output predictive models were used to compute indices that quantify relevant physiological mechanisms and compare differences between MCI patients (MP) and control subject (CS).ResultThe obtained model‐based indices were significantly different for MP vs. CS with regard to the dynamic relationships between CTO and etCO2 or TV changes. This is illustrated in Figure 1, where the average model‐kernels (representing the CTO response to a unit‐impulse change of etCO2 or TV) are shown for 40 MP (red line) and 15 CS (blue line), along with SD bounds (dashed lines). Improved delineation between MP and CS resulted (p<0.001) when the obtained model‐based indices of Dynamic Vasomotor CO2 Reactivity (DVCR) and Dynamic Cortical Oxygenation Reactivity (DCOR), respectively, were combined in a composite index defined by the Fisher Discriminant of the respective scatter‐plot (see Figure 2).ConclusionDysregulation of cerebral/cortical perfusion can be detected early and quantified through dynamic predictive modeling of spontaneous hemodynamic/respiratory time‐series data, allowing delineation between MCI patients and controls (p< 0.001) for improved MCI diagnosis. This is viewed as an indication that such dysregulation of cerebral perfusion may be an early trigger/link in the pathogenic cascade towards neurodegenerative disease.
Carotid stiffness is associated with brain amyloid‐β burden in amnestic mild cognitive impairment
Authors: Zhang Rong 
Published: December 2020

AbstractBackgroundVascular dysfunction has been implicated in the onset and progression of Alzheimer’s disease (AD), yet the relationship of arterial stiffening with brain amyloid‐β burden in at risk patients is unclear.ObjectiveWe aimed to determine the relationship of aortic and carotid arterial stiffening with Aβ burden in patients with amnestic mild cognitive impairment (aMCI), a proposed transitional stage between normal aging and AD.MethodsThirty‐two older adults with aMCI underwent 18Florbetapir PET amyloid imaging to ascertain Aβ burden via standardized uptake value ratio (SUVR). Carotid‐femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, and carotid β stiffness index and distensibility, which reflect local cerebral arterial stiffness, thus having direct impact on the cerebral circulation, were measured using applanation tonometry and ultrasonography.ResultsRegion‐of‐interest based analysis showed that precuneus and mean cortex Aβ SUVR were correlated positively with carotid β stiffness index and negatively with carotid distensibility after adjusting for age, sex, mean arterial pressure (MAP), pulse pressure (PP) and APOE4 status. Whole‐brain voxel‐wise analysis showed that Aβ SUVR was positively correlated with carotid β stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aβ SUVR.ConclusionsCarotid rather than aortic stiffening is independently associated with brain Aβ burden in patients with aMCI after adjusting for age, sex, MAP, PP, and APOE4 status. These findings provide evidence that arterial stiffening, particularly carotid artery stiffening, may contribute to AD pathology in patients with aMCI. Trial Registration: ClinicalTrials.gov identifier: NCT01146717.
ExploreQC: A toolbox for MRI quality control in the EPAD multicentre study
Authors: Lorenzini Luigi , Ingala Silvia , Wottschel Viktor , Wink Alle Meije , Kuijer Joost , Sudre Carole H , Haller Sven , Molinuevo Jose Luis , Gispert Juan Domingo , Cash David M , Thomas David L , Vos Sjoerd , Petr Jan , Wolz Robin , Pernet Cyril , Waldman Adam , Barkhof Frederik , Mutsaerts Henri JMM ,   the EPAD Consortium
Published: December 2020

AbstractBackgroundMagnetic Resonance Imaging (MRI) of the brain is prone to artefacts that may worsen image quality and subsequent analyses. Despite the growing number of large‐scale multi‐institutional imaging studies, standardized approaches for defining inclusion and exclusion criteria on the basis of image data quality are still lacking and quality assessment is often based on visual inspection. We introduce ExploreQC, a MATLAB‐based toolbox which implements a semi‐automatic pipeline to assess QC metrics, select the most relevant parameters, and to derive informed inclusion thresholds.MethodsThe efficacy of ExploreQC was demonstrated on scans from 436 participants of the multi‐centre European Prevention of Alzheimer’s Dementia (EPAD) longitudinal cohort study. Five different MRI sequences from five sites of the EPAD study were used: structural (T1w, FLAIR, diffusion MRI), resting state functional (rs‐fMRI) and ASL perfusion MRI. For each sequence, QC features were selected following a literature review of recently published studies on multi‐parameter QC (Alfaro‐Almagro, F. et al. 2018; Bastiani, M. et al. 2019; Esteban, O. et al. 2017; Fallatah, S. M. 2018; Shehzad, Z. 2015). Similar parameters were grouped in image feature domains (IFDs).ResultsTable 1 shows the 38 QC features within 19 IFDs computed in the EPAD cohort covering each MRI scan‐type. ExploreQC generated within‐ and between‐site distribution plots of each QC parameter to identify outliers for subsequent visual inspection in order to establish the relevance of the parameter (Fig 1).ConclusionsExploreQC facilitates the computation and visualization of informative QC parameters, within and between sites and modalities. Application of ExploreQC to the EPAD data showed that the investigation of distributions of different quantitative QC features can provide an overview of the general quality of the data, identify outliers and derive informed reference thresholds for exclusion criteria.
Alzheimer's genetic risk factor FERMT2 (kindlin‐2) controls axonal growth and synaptic plasticity in an APP‐dependent manner
Authors: Eysert Fanny , CoulonVreulx AudreyAnais‐Camille , Flaig Amandine , Mendes Tiago , Grenier‐Boley Benjamin , Demiautte Florie , Amouyel Philippe , Dumont Julie , Kilinc Devrim , Lambert Jean‐Charles , Chapuis Julien 
Published: December 2020

AbstractBackgroundAlthough APP metabolism is being intensively investigated, a large fraction of its modulators are yet to be characterized. In this context, we combined two genome‐wide high‐content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved.MethodWe combined genome‐wide high‐content screenings to identify miRNAs (n = 2,555) and target genes (n = 18,107) involved in the APP metabolism. To predict the function(s) of miRNAs that target these genes, pathway enrichment analysis was performed using DIANA Tools mirPath (v3.0). CRISPR/Cas9 technology has been used to generate HEK293 cell lines carrying rs7143400 variant located in the FERMT2 3’UTR and its impact on miRNA binding. Involvement of FERMT2 in axonal growth and synaptic connectivity was assessed using primary neurons cultured in microfluidic devices that fluidically isolate axons from their cell bodies. The functional impact of FERMT2 on CA1 basal synaptic transmission and long‐term potentiation (LTP) has been recorded in ex vivo mouse hippocampal slices, after stereotactic lentivirus injection allowing expression of shNT, shFERMT2 or shAPP.ResultOur systematic approaches led us to characterize 180 genes targeted by 41 miRNAs as modulators of APP metabolism. Among these genes, we focused on FERMT2, a known genetic risk factor of sporadic AD. We found that FERMT2 directly interacts with APP to modulate its metabolism and that FERMT2 under‐expression impacts axonal growth, synaptic connectivity and long‐term potentiation in an APP‐dependent manner.Lastly, the rs7143400‐T allele, which is associated with an increased AD risk and localized within the 3’UTR of FERMT2, induced a down‐regulation of FERMT2 expression through binding of miR‐4504. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls.ConclusionAltogether, our data provide strong evidence for a detrimental effect of FERMT2 under‐expression in neurons and insight on how this may influence AD pathogenesis.