bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of endogenous Aβ in plasma of patient with Alzheimer’s disease differentiates Aβ oligomerization tendencies caused by synthetic Aβ
Authors: Choi Youngki , Yu Ji Sun , Joh Yechan , Kang Sungmin , Youn Young Chul , An Seong Soo , Kim Sangyun 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. A number of studies have presented accumulating evidence that oligomeric amyloid‐β (Aβ) is the major factor in the AD pathogenesis. To detect oligomeric Aβ, Multimer Detection System‐Oligomeric Amyloid‐β (MDS‐OAβ), a technique for measuring Aβ oligomerization in plasma to diagnose AD was previously developed. In this study, In this study, we aim to evaluate the role of the seeding effect in plasma in differentiating between AD and individuals without AD pathology.MethodPlasma was spiked with synthetic Aβ peptides and incubated to confirm the tendency of Aβ oligomerization in AD samples and samples without AD pathology. AlphaLISA assay was performed in comparison with MDS‐OAβ to confirm the relationship between endogenous Aβ and spiked synthetic Aβ peptides in plasma. In addition, Aβ immuno‐depletion in plasma confirmed the effect of synthetic Aβ peptides on the Multimer Detection System (MDS) signals.ResultThe difference in the seeding effect between AD plasma and normal control plasma was confirmed. AlphaLISA assay presented that synthetic Aβ peptide recruits endogenous Aβ in plasma and the seeding effect is significantly increased in AD plasma than normal control plasma. In addition, the absence of the MDS signals in Aβ‐depleted plasma supported that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aβ in plasma. MDS‐OAβ can differentiate between AD patients and non‐AD controls by measuring the degree of Aβ oligomerization after spiking synthetic Aβ into plasma samples with incubation.ConclusionSpiking of synthetic Aβ peptides had a greater seeding effect in AD plasma than in normal control plasma. Therefore, the measurement of Aβ oligomerization in plasma using MDS‐OAβ has high utility in AD diagnosis.
Why don’t Alzheimer’s disease patients know that they forget?
Authors: Razafimahatratra Solofo , Guieysse Thomas , Medani Takfarinas , Lejeune François‐Xavier , Houot Marion , George Nathalie , La Corte Valentina , Klarsfeld André , Dreyfus Gérard , Pantazis Dimitrios , Dubois Bruno , Andrade Katia 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) patients are often unaware of their memory deficits even at early stage of disease. Anosognosia has been related to frontal dysfunction although its underlying neural mechanism is still unknown. We hypothesized that it may result from an inability to monitor ongoing behavior due to a failure in the error‐monitoring system. Our main objective was to study this system in individuals at risk for AD.MethodThe study involved the 318 cognitively normal individuals of the INSIGHT cohort. All were age 70 and over at entry with a known brain amyloid status assessed by PET. We recorded the error negativity (ERN) and error positivity (Pe) of event‐related potentials (ERPs) in each of these individuals annually over 5 years. The cognitive task was the recognition of words, which had been memorized one hour before. ERPs were obtained by averages that were time‐locked to the erroneous response. All differences were tested through linear mixed‐effects models with group (Prog A+, NotProg A+; i.e., amyloid positive individuals who progressed or not to AD) and time (M0, M60, or Mdiag; i.e., months from study admission or month of AD diagnosis), as well as interaction between both as fixed effects, the subject identifier as a random effect to account for the paired measurements at M0 and M60 or Mdiag, and inclusion of age at M0 for covariate adjustment. Post hoc tests were performed on the interaction.ResultOur study focused on two subgroups identified after 5 years of follow‐up: 1) amyloid positive (A+) individuals who progressed to AD (Prog A+, n=15); and 2) A+ individuals who did not progress to AD (NotProg A+, n=35). When compared to M0 for intragroup analysis or to M60 for intergroup analysis, the Prog A+ group at Mdiag displayed significantly slower reactions and higher error rates, and its Pe amplitude was also significantly lower.ConclusionOur results indicate the existence of a monitoring system failure in early stages of AD, which may be the substrate of anosognosia.
Age‐dependent functional connectivity changes across large‐scale brain networks disrupt memory consolidation processes
Authors: Fassbender Ronja V. , Risius Okka , Dronse Julian , Nellessen Nils , Richter Nils , Fink Gereon R. , Kukolja Juraj , Onur Oezguer A. 
Published: December 2021

AbstractBackgroundEpisodic memory decline characterizes “normal” aging but is also a core symptom of Alzheimer’s disease. Therefore, considerable efforts have been undertaken to study this memory domain and its neural substrates. Recent studies have mainly focused on encoding‐ and retrieval‐ related processes. However, some findings suggest that episodic memory deficits are at least in part due to impaired consolidation processes.MethodsWe investigated age effects on consolidation‐related functional network changes and their vulnerability to cognitive interference, using fMRI data of 13 young (20–30 years) and 16 senior (49–75 years) participants. FMRI scanning was performed prior to and during a spatial memory paradigm, consisting of encoding, consolidation, and retrieval phases. To ensure that the observed connectivity changes were due to consolidation processes, the consolidation phase was manipulated over two sessions: (1) no manipulation and (2) repeated stimulus‐presentation with interfering spatial context information.ResultsWe compared the fractional amplitude of low‐frequency fluctuations (fALFF) to analyze spontaneous brain activity changes from pre‐ to post‐encoding rest. In the control condition, fALFF decreased within left supramarginal gyrus (SMG), right middle temporal gyrus (MTL), and left precuneus (Pc), whereas, fALFF increased within parts of the occipital and inferior temporal cortex. To evaluate the integration in large‐scale brain networks, connectivity analyses between the fALFF‐derived seeds and network ROIs were performed. We observed significant coupling between consolidation‐related brain regions and large‐scale brain networks during consolidation, with connectivity between the SMG and large parts of the memory network modulated by aging. There was also a disruptive effect of interference on connectivity between the Pc and parts of the salience network. Of particular importance for successful consolidation, however, is the connectivity between parts of the occipital lobe, the inferior and middle temporal gyrus. Connectivity within this network, which corresponds to the ventral visual stream, may predict subsequent memory performance. The predictive value appears to be higher in young than in seniors.ConclusionOur results support the assumption that age‐related memory decline is at least partly caused by impaired consolidation processes. We showed that consolidation requires a complex interplay between large‐scale brain networks, which is partially disrupted by aging and thus becomes insufficient.
Association of body mass index with brain structure and biomarkers of inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid pathology
Authors: Grau‐Rivera Oriol , Sala‐Vila Aleix , Operto Greg , Garcia Marina , Arenaza‐Urquijo Eider M , Suarez‐Calvet Marc , Sánchez‐Benavides Gonzalo , Milà‐Alomà Marta , González‐de‐Echávarri José Maria , Minguillón Carolina , Suridjan Ivonne , Kollmorgen Gwendlyn , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Gispert Juan Domingo ,   ALFA Study
Published: December 2021

AbstractBackgroundObesity has been linked to brain atrophy and peripheral inflammation. However, the association between body mass index (BMI) and brain structure can be confounded by Alzheimer’s disease (AD) pathology‐related weight loss, and its association with neuroinflammation remains unknown. We explored associations of BMI with brain structure and biomarkers of peripheral and central nervous system inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid (Aβ) pathology.MethodWe analyzed data from 385 ALFA+ study participants. We measured plasma C‐reactive protein (CRP), CSF p‐tau and t‐tau with the Elecsys® immunoassays and CSF Aβ42, Aβ40 and neuroinflammation biomarkers (sTREM2, GFAP, YKL40, S100 and IL6) with the exploratory Roche NeuroToolKit robust prototype assays. We used separated linear regression models to analyze associations of BMI with plasma CRP, CSF AD and neuroinflammation biomarkers, and mean cortical thickness (CTh) in a composite AD signature region. We explored voxelwise associations (p<0.001, k=100) between BMI and gray matter volume (GMv) with SPM12. We stratified all analyses by Aβ status (defining positivity as Aβ42/40<0.071) and adjusted by age, sex, systolic blood pressure, triglyceride, glycated hemoglobin and physical exercise levels.ResultBMI was positively associated with CRP levels in Aβ‐ and Aβ+ groups (p<0.001). We found no significant associations between BMI and CSF AD or neuroinflammation biomarkers. BMI was negatively associated with mean CTh in the AD signature region in the Aβ‐ (p<0.001), but not in the Aβ+ group (p=0.543). Voxel‐based morphometry analyses showed widespread negative associations between BMI and GMv in Aβ‐ participants involving bilateral prefrontal, medial temporal, parietal, occipital, thalamic and cerebellar regions (Figure 1), without positive associations. Among Aβ+ participants, we found positive associations with BMI in small clusters in the cerebellum, middle frontal and anterior cingulate gyri (Figure 2), without negative associations.ConclusionIn the absence of Aβ pathology, higher BMI is associated with brain atrophy involving AD‐related areas, suggesting that midlife obesity may increase dementia risk by mechanisms unrelated to AD pathology. Conversely, among individuals on the AD continuum, higher BMI appears to be associated with more preserved brain structure. We found no evidence of an association between higher BMI and neuroinflammation.
Eye‐tracking task detects early executive function deficits in presymptomatic frontotemporal dementia
Authors: Russell Lucy L , Convery Rhian S , Greaves Caroline V , Kaski Diego , Rohrer Jonathan D 
Published: December 2021

AbstractBackgroundAs research moves from understanding the natural history of frontotemporal dementia (FTD) to therapeutic trials, reliable and valid psychological measures are required to assess the efficacy of treatments. Current psychometric tests have only been able to identify subtle changes in genetic FTD around 5 years before the onset of symptoms suggesting more sensitive tasks are required.MethodThe aim of this study was to investigate whether an anti‐saccade eye‐tracking task could detect impaired executive function in a cohort of individuals that are at‐risk of developing genetic FTD. A total of 18 mutation carriers (MCs) and 20 mutation negative control participants completed the task, being instructed to look in the opposite direction to the red dot when it appeared on the screen. There were eight trials in the horizontal direction at 5 and 8 degrees of visual angle (°VA) and four trials in the vertical condition at 5°VA. The number of correct and self‐corrected anti‐saccades was calculated and a linear regression, covarying for sex, was used to assess performance between mutation carriers and controls.ResultOf the 18 mutation carriers, 8 had expansions in chromosome 9 open reading frame 72, 6 had progranulin mutations and 5 had mutations in microtubule‐associated protein tau. The mean age for the mutation carriers group overall was 33.2 years, and 34.3 for the control group. The mutation carriers had significantly fewer correct anti‐saccades than the control group when the stimuli was presented in the vertical direction (MCs: mean = 1.44, SD = 1.29; controls: 2.32, 0.95; p = 0.016). There were no significant differences observed in the number of correct anti‐saccades in the horizontal direction, nor in the number of self‐corrected anti‐saccades made in either direction.ConclusionThis preliminary study suggests that early executive function deficits can be detected presymptomatically in FTD using an anti‐saccade eye‐tracking task. It is possible that tasks like this, using eye‐tracking with very simple instructions, may be able to help assess the efficacy of therapeutic trials in the near future.
Independent effects of white matter hyperintensities on frailty among individuals with Alzheimer's disease
Authors: Yang Hyun‐ju , Park Joon Hyuk 
Published: December 2021

AbstractBackgroundWith an aging global population, recent years have seen rapid expansion in the attention of the frailty. Thus, understanding, and determinant the potentially modifiable risk factor for frailty is a major concern for health care policy and provision.MethodSubjects were recruited for the study from the dementia clinic of Jeju National University Hospital between January 2018 and January 2020. All of the subjects were evaluated by using CERAD‐K and diagnosed probable AD and possible AD by a panel of two experienced dementia research neuropsychiatrists. WMH volume was calculated using automated segmentation analysis and further partitioned into three categories (Kim, BIOL PSYCHIATRY 2008). Frailty evaluated by Korean Frailty Index (KFI) and classified into three categories according to the cutpoints. Other physical performances such as BMI, muscle mass index, grip strength, and gait speed measures were performed by experienced researchers specialized in geriatric assessment. comorbidity status using the Charlson comorbidity index, and depressive symptoms using GDS was examined.ResultIn total, 34 subjects (23.6 %) were classified as frail 47 subjects (32.6 %) were classified as prefrail, and 63 subjects (43.8 %) were classified as a non‐frail group. The frail group had higher WMH volume compared to the non‐frail group (p=0.002), and these trends remained significant after linear regression analyses. According to the new subclassification of WMH, using the non‐frail group as a reference, total WMH volume (OR=6.297, p=0.013), JVWMH volume (OR=12.955, p=0.014), and PVWMH (OR=3.382, p=0.025) were associated with frail. Furthermore, according to the path model, only the gait speed mediated the association between WMH and frailty.ConclusionIn our study provides evidence of a cross‐sectional relationship between WMH and frailty, and there is a difference in the association between the subclassification of WMH volume and frailty. Furthermore, we suggest that gait speed could be a useful biomarker for assessment of the frailty.
What elements are important in current treatment and care guidelines to provide culturally sensitive care for people with a migration background with dementia? A systematic analysis
Authors: Schmachtenberg Tim , Monsees Jessica , Thyrian Jochen René 
Published: December 2021

AbstractBackgroundAmong people with a migration background, problems such as underdiagnosis of dementia and underprovision are more widespread than in people without a migration background. The development of guidelines for culturally sensitive care of this population can be the first important action to address these inequalities. This article aims to provide a systematic overview of the key elements and measures regarding culturally sensitive care referred to in papers, reports, and guidelines.MethodUsing a triangulation of the models from a systematic literature analysis by Becker (2018), discourse analysis by Keller (2011), and qualitative content analysis by Mayring (2014), written statements from n=64 documents and oral statements from n=4 events were collected, paraphrased, and coded.ResultGuidelines for the care of people with a migration background and dementia should focus on these topics: raising awareness in migrant communities about dementia and available healthcare services; building structures that promote the intercultural opening of healthcare systems; ensuring early and valid dementia diagnosis among people with a migration background; supporting, informing, and training care providers; overcoming communication barriers between care providers and people with a migration background with dementia; ensuring unrestricted access to healthcare for people with a migration background; providing culturally and linguistically sensitive support, care and treatment of people with a migration background with dementia; and conducting research on the care situation of this population.ConclusionDue to the specific needs and the particular challenges regarding the care of people with a migration background with dementia, which require a specific healthcare strategy with a comprehensive set of measures, the development of separate guidelines for the care of people with a migration background with dementia at the national level is recommended. In addition, the development of European guidelines for culturally sensitive care of people with a migration background with dementia can be an instrument for reducing dementia‐specific care inequalities. As a first step, a consensus on the definition of the term "migrant" should be sought at the European level.
Maintain Your Brain trial: Early findings and lessons learned from adherence and compliance data
Authors: Brodaty Henry , Heffernan Megan , Anstey Kaarin J , Fiatarone Singh Maria A , Jorm Louisa , Lautenschlager Nicola T , Maeder Anthony , McNeil John , Sachdev Perminder S , Valenzuela Michael , Chau Tiffany ,   Maintain Your Brain Collaborative Team
Published: December 2021

AbstractBackgroundTechnology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia. Key issues in online interventions are recruitment and retention. To devise strategies to improve population reach We investigated which factors influence recruiting and maintaining participants in such an intervention, the in‐progress Maintain Your Brain trial.MethodInvitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). For MYB, participants were required to be eligible for at least one of four modules to be enrolled (physical activity, nutrition, brain training and mental wellbeing). All participants received modules based on their risks and were randomly allocated to either personalised coaching (intervention) or static information (control). Associations between participant characteristics (listed Table 1) and likelihood of completing set assessment tasks was assessed at two key stages – end of baseline and end of 12‐month follow‐up using stepwise (forward) regression.ResultsOf 96,418 people invited, 12,281 (13%) participants started baseline and completed a mean of 6.2 (SD 4.3) of ten assessments. Of these, 6,236 (6%) were enrolled in the trial. At 12‐months participants completed a mean of 5.0 of 8 assessments (SD = 3.8). Completion rate of the primary outcome (two tasks) was 62% (3,869). In the final regression model for baseline (Table1), overall associations were weak even though statistically significant, with only years of education not entered in the final model. The follow‐up model included retirement status, gender, baseline dementia risk and baseline wellbeing. However, this model (df1 = 1, df2 =6231; R2 = .01) accounted for even less variation than baseline model (R2 = .04).ConclusionOverall, regression models of participant characteristics accounted for a low amount of variation in task completion rates at both baseline and follow‐up. Participants were less likely to complete baseline tasks if they were older, male, not living with a spouse or alone and not retired or had lower dementia risk score and more psychological distress.
Prevalence of dementia in people with migration background in Europe
Authors: Monsees Jessica , Schmachtenberg Tim , Thyrian Jochen René 
Published: December 2021

AbstractBackgroundThe proportion of elderly people with migration background increases, therefore it can be assumed that the proportion of people with migration background and dementia will increase as well. So far, prevalence data for dementia and migration on an European level is only scarcely available. This study is part of a project to create an EU‐atlas on dementia and migration and depicts the prevalence data on dementia and migration in the 27 EU and 4 EFTA member states as well as the UK.MethodPrevalence data will be estimated based on dementia prevalences of the country the people are living in and the number of people with a migration background from different ethnicities in that country.ResultAn extensive collection of information about dementia and migration depicting prevalence of dementia in people with a migration background on a European level will be provided.ConclusionObtaining this information can help to uncover gaps in the health care systems and communities on an European level by highlighting a vulnerable population that is not receiving the attention and support that it needs. This can serve as a starting point to see where action must be taken and may therefore lead to better health care for people with migration background and dementia.
Exploring discordant data in dementia clinical trials
Authors: Kott Alan , Miller David S. 
Published: December 2021

AbstractBackgroundWe have observed numerous apparent inconsistencies in direction of scale (eg – MMSE, ADAS‐Cog and CDR) change between visits across multiple dementia clinical trials. While all instruments are not expected to move in the same direction, clinically meaningful changes in opposite directions may signal scoring and/or administration errors in one or more scales. In this analysis, we explore a) the extent to which such discordances between the MMSE, ADAS‐Cog and CDR occur in dementia clinical trials, and b) whether any associations between the presence of such discordances and scoring and/or administration errors exist.MethodBlinded data were obtained from multi‐national dementia clinical trials in early AD. Visit‐to‐visit point change was calculated for the MMSE, ADAS‐Cog and CDR‐sb. Clinically meaningful changes were defined as ≥ 4 points for the ADAS‐Cog, 3 points for the MMSE and 1 point for the CDR‐sb. We defined discordance occurring when at least 2 of 3 instruments showed clinically meaningful change, but in opposite directions. We also evaluated data from the corresponding Endpoint Quality reviews of both the worksheet and audio recordings of these assessments. These were performed by calibrated, independent Clinicians and assessed whether there were any administration and/or scoring errors. Descriptive statistics and logistic regression analyses were used to address our questions.ResultData were collected from 4,892 randomized subjects. Visit‐to‐visit discordances were identified in 1,732 out of 15,321(11.30%) collected visits. Discordances were significantly less likely at baseline than after randomization (OR=0.54; CI=0.49‐0.61). The presence of baseline discordances significantly increased the odds of post‐baseline discordances (OR = 1.7; CI=1.4‐2.1). No association between the presence of discordances and administration or scoring errors was identified.ConclusionWe have identified over 11% of study visits affected by clinically meaningful discordances between the visit‐to‐visit changes between the MMSE, ADAS‐cog and CDR‐SB. Despite the expected lower presence of baseline than post‐baseline discordances, discordances at baseline affected over 8% of randomized subjects. The lack of association between the discordances and administration or scoring errors is surprising and we plan further analyses to understand this phenomenon better.