bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain donation for research: Features of the brain donors from the InveCe.Ab population‐based cohort
Authors: Davin Annalisa , Rolandi Elena , Poloni Tino Emanuele , Medici Valentina , Vaccaro Roberta , Cirrincione Alice , Cereda Cristina , Guaita Antonio 
Published: December 2021

AbstractBackgroundResearch on brain tissue is essential to understand the biological mechanisms underlying neurodegenerative diseases and brain aging processes.Brain donation for research is influenced by many factors both in clinical and non‐clinical samples. The aim of the present study is to explore the features associated with the decision to join the brain donation program of the Abbiategrasso Brain Bank (ABB) in the context of a population‐based study on brain aging.MethodThe longitudinal cohort study InveCe.Ab enrolled participants aged 70‐75 years and residing in Abbiategrasso (MI). During the second follow‐up of the study (2014), the participants fill a questionnaire to investigate attitudes through brain donation for research purpose (N=1010). We compared socio‐cultural aspects and questionnaire responses between participants who adhere to brain donation (N=163; 16,1%) and those who refuse (N=847) using Student’s t Test and chi‐squared test when appropriate. Variables showing significant differences in the group comparisons were included in a logistic regression model with brain donation status (yes/no) as the dependent variable.ResultThe groups were comparable for age and sex, while ABB donors were significantly more educated (donors: 7,74, non‐donors: 6,70; p=0,000), more frequently prone to organ donation (donors: 93,4%; non‐donors: 64,3%, p=0,000) and to cremation (donors: 76,8%; non‐donors: 44,8%; p=0,000). Among those who were favorable for brain donation in the questionnaire, only 43,6% actually signed up for brain donation (p=0,000). Moreover, brain donation was associated with friends relationship satisfaction (donors: 96,5%; non‐donors: 91,4%; p=0,023) and better self‐reported health (donors: 83,3%; non‐donors: 73,4%; p=0,028), despite no difference between groups was found in the number of chronic disease (p=0,49). Finally, in the multivariable model, being prone to organ donation was the main factor associated with actual registration for brain donation. The availability for cremation remained significant only for males.ConclusionDespite a positive attitude through brain donation in nearly half of the respondents, only a minority of older adults actually engage in a brain donation program. Being prone to organ donation was the main factor associated with brain donation subscription. The donors were more educated, with a positive attitude through their health and their relationships with friends.
Young‐onset dementia in memory clinics in the Netherlands: PRECODE‐GP
Authors: Rhodius‐Meester Hanneke FM , Leeuwis Anna E , Van Gils Aniek M , Bakker Christian , Peetoom Kirsten , Bouwman Femke H , Pijnenburg Yolande AL , de Vugt Marjolein , van der Flier Wiesje M ,   the PRECODE‐GP Consortium
Published: December 2021

AbstractBackgroundThe disease trajectory of patients with young onset dementia differs from older patients, as do healthcare requirements. To improve specialized care, more insight in young onset dementia is crucial. The aim of PRECODE‐GP is therefore 1) to conduct an (annual) inventory of the diagnostic workup in all memory clinics in the Netherlands, and 2) to set up a prospective nationwide database including newly diagnosed younger patients with dementia.MethodsPRECODE‐GP is part of the PRECODE project, a collaboration between four Dutch Alzheimer centers, Knowledgecenter Dementia at Young Age, Nivel and Alzheimer Nederland. Governance is embedded in the Dutch Memory Clinic Network. Memory clinics are asked annually to fill out a survey on their current diagnostic workup. Eligible patients (<70 years; any type of dementia) are identified by local specialists and recruited via an informed consent procedure providing consent for future linkage to other datasets. Demographics, test results and (etiological) diagnosis are collected in an online database.ResultsPRECODE‐GP was initiated in July 2019 and has been approved in 36 memory clinics, approval procedure is ongoing in additional 10 clinics. Based on the annual survey (filled out by 21 clinics), standard imaging of the brain occurs in almost half of memory clinics and neuropsychological examination in one third. CSF is performed when deemed necessary by the clinician. A median 250(141‐396) new patients visited the memory clinics yearly, of whom 111(74‐180)(48%) were diagnosed with dementia and 12(4‐36)(6%) were <70 years. To date, 201 young onset dementia patients (age 62±8, 51% female, MMSE 22±5) are included in our prospective database, diagnosed with 140(69%) Alzheimer’s dementia (AD), 29(14%) frontotemporal dementia (FTD), 14(7%) dementia with Lewy Bodies (DLB) and 18(9%) other dementia types. Patients with FTD were youngest (61±6 years), subjects with DLB were most often male (79%), in AD MMSE was lowest (21±5).ConclusionWe took the first step to include patients with young onset dementia via all Dutch memory clinics. As a next step, we plan to link data to existing registries, to gain valuable knowledge on disease trajectories. All needed to improve quality of life for patients with young onset dementia.
Exploration of the cognitive functions of females in a mouse model of chronic neuroinflammation
Authors: Wagnon Ingrid Marguerite , Niedermayer Garry , Chesworth Rose , Muench Gerald Wolfgang , Karl Tim , Gyengesi Erika 
Published: December 2021

AbstractBackgroundChronic neuroinflammation has been identified as a common feature of many neurodegenerative diseases, such as Alzheimer’s disease (Kempuraj et al., 2016). Sex has been shown to strongly influence the development as well as the clinical expression of neurodegenerative and neuroinflammatory diseases . The GFAP‐IL6 mouse is a useful model to study chronic neuroinflammation and its consequences. These mice exhibit increased levels of neuroinflammatory markers, neurodegeneration, as well as motor deficits (Campbell et al., 1993; Chiang et al., 1994; Gyengesi et al., 2019). Although previous studies have identified some cognitive impairments in these animals (Heyser et al., 1997), more work is needed to fully characterised this model at a behavioural level.MethodCognitive tests exploring anxiety such as the elevated plus‐maze (EPM), light/dark box, and spatial learning and memory such as the Barnes maze and Y‐maze, were performed on female GFAP‐IL6 mice and their litter mate control wild‐type (WT) from 12 months of age. Tests were recorded using AnyMaze® and results analysed in IBM SPSS® software with one or two‐way ANOVAs. This study was completed with immunochemistry and RT‐qPCR in brain regions implicated in anxiety, learning and memory.ResultWe found that the GFAP‐IL6 mice travelled a significantly higher percentage of distance in the opened arm of the EPM than the WT (WT=9.48%, GFAP‐IL6=18.03%, p<0.01), and a lower percentage in the closed arm than the WT (WT=63.13%, GFAP‐IL6=53.70%, p<0.05). No genotype effect was found in the preference for the light compartment during the light/dark box test. In the Y‐maze, the GFAP‐IL6 mice spent a significantly lower percentage of time in the novel arm compared to the WT (WT=45.06%, GFAP‐IL6=27.97%, p<0.01). During the acquisition phase of the Barnes maze, all mice were able to learn the location of the escape hole. However, there was a significant effect of genotype (p<0.01), with the GFAP‐IL6 mice exhibiting higher latencies to enter the escape hole than the WT. No significant difference was found during the probe testConclusionThese results suggest that female GFAP‐IL6 mice exhibit a less anxious phenotype but seem to present impaired spatial memory compared to female WT.
Plasma and cerebrospinal fluid neurofilament light protein concentrations are differentially associated with biomarker evidence of neurodegeneration in a community‐based population of 70‐year‐olds
Authors: Dittrich Anna , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Zettergren Anna , Simrén Joel , Schöll Michael , Westman Eric , Skoog Ingmar , Kern Silke 
Published: December 2021

AbstractBackgroundNeurofilament light protein (NfL) is the best‐established fluid biomarker for general neurodegeneration, predicting poor outcome in cognitive function across neurodegenerative dementias. Currently, there are few studies examining the correlation of plasma and cerebrospinal fluid (CSF) NfL with other fluid and imaging biomarkers for neurodegeneration.MethodThe sample (n= 287) was derived from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016. CSF NfL, total‐Tau (t‐Tau), phospho‐Tau (p‐Tau), neurogranin, CSF/serum albumin ratio and plasma NfL were measured and brain magnetic resonance imaging (MRI) was conducted. Participants were examined with comprehensive neuropsychiatric and somatic examinations, and dementia was diagnosed according to DSM III criteria. In linear models adjusted for age and sex, NfL was examined in relation to other demographics, cognitive tests, CSF biomarkers and MRI measurements. Sub analysis were also performed on participants with or without β‐Amyloid pathology, defined as a CSF β‐Amyloid 42 ≤ 530 pg/mL.ResultNfL in plasma and CSF presented a moderate correlation (Spearman’s R=0.41, p<0.001). P‐NfL was associated with worse delayed memory recall (p=0.019), smaller hippocampus volume (p=0.001), larger white matter lesion volume (p=0.004), as well as CSF levels of β‐amyloid 42 (p=0.043), β‐amyloid 42/40 (p=0.049), β‐amyloid 42/t‐Tau (p=0.007), CSF NfL (p<0.001) and BMI (p<0.001). CSF NfL was associated with t‐Tau (p=0.001), p‐Tau (p<0.001), neurogranin (p=0.014), albumin ratio (Qalb) (p=0.001), P‐NfL (p<0.001), and BMI (p=0.033). In participants with prevalent β‐amyloid 42 pathology, P‐NfL was associated with β‐amyloid 42 (p=0.009), β‐amyloid 42/40 (p=0.043), β‐amyloid 42/t‐Tau (p=0.010) and CSF NfL (p<0.001). In participants without β‐amyloid 42 pathology, P‐NfL associated with BMI (p<0.001), smaller hippocampus volume (p=0.007) and CSF NfL (p<0.001).ConclusionAlthough CSF NfL and P‐NfL concentrations are correlated, the biomarker measured in the two sample types presents distinct associations with biomarker evidence of AD pathology and neurodegeneration. P‐NfL was associated with several markers that are characteristic of AD, whereas CSF NfL demonstrated more associations with synaptic and neurodegeneration.
Informant‐reported subjective cognitive decline is specifically relevant in MCI patients: Association with cognition, amyloid deposition and neurodegeneration
Authors: Kuhn Elizabeth , Perrotin Audrey , Touron Edelweiss , Dautricourt Sophie , Vanhoutte Matthieu , Vivien Denis , De la Sayette Vincent , Chetelat Gaël ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2021

AbstractBackgroundInformant‐reported subjective cognitive decline (I‐SCD) have been associated with objective cognitive decline and biomarkers of Alzheimer's disease (AD) in previous studies. However, we lack a comprehensive overview of these associations across the entire clinical continuum of the Alzheimer's syndrome allowing to stress whether there is a clinical stage where this measure is particularly relevant. This study aims at describing the relationships of I‐SCD to cognition and multimodal neuroimaging data within two independent cohorts.MethodWe used data from 110 participants from IMAP+, and, as an independent replication cohort, from 731 participants from ADNI. All participants were divided into four clinical groups (IMAP+/ADNI): controls (N=32/157), subjective cognitive decline (SCD; N=25/84), mild cognitive impairment (MCI; N=35/369) and dementia (N=18/121). We first compared the I‐SCD score between groups and assessed its relationship to cognition within each clinical group cross‐sectionally and longitudinally (over 2.5 years). We then assessed the voxelwise relationships between the I‐SCD score and neuroimaging measures of amyloid deposition (Florbetapir‐PET) and neurodegeneration, i.e. atrophy (T1‐MRI) and hypometabolism (FDG‐PET), across the four clinical groups. These analyses were performed in IMAP+ and replicated in the ADNI cohort.ResultsThe I‐SCD score was higher from one clinical group to another within both cohorts (p?0.001, except SCD‐MCI p=0.15 in IMAP+). Interestingly, this measure was associated with cognition and AD biomarkers specifically within the MCI patients. The relation was such that higher I‐SCD was associated with lower memory and global cognition cross‐sectionally and over time (Figure 1), higher amyloid deposition (global SUVr and voxelwise) and higher neurodegeneration (Figure 2). The same findings were recovered in both cohorts, except for neurodegeneration where the links were significant in ADNI only.ConclusionOur findings reveal that the cognitive decline reported by the informant is particularly meaningful at the MCI stage, when the corresponding self‐reported score is contaminated by decreased awareness. The strong and consistent links with cognition and AD biomarkers found here reinforce the validity and clinical relevance of this finding and suggest that this measure should be used in clinical trials to identify MCI patients at higher risk to develop cognitive decline and/or AD.
INSPIRATION: Study design and preliminary results of a crosssectional risk AD‐profiling study
Authors: Zeyen Philip , Sannemann Lena , Escher Claus , Müller Theresa , Jessen Frank 
Published: December 2021

AbstractBackgroundEstimates suggest that between 30% and 40% of all AD cases are attributable to potentially modifiable risk factors such as hypertension, midlife obesity, diabetes mellitus, depression, social isolation, physical inactivity, smoking, low level of education, and hearing loss (Barnes and Yaffe 2011; Livingston et al. 2020; Luck and Riedel‐Heller 2016). In addition, other risk factors for AD such as stress and sleep disturbances have been identified in recent years (Escher et al. 2019; Sindi et al. 2018). The Individual risk profiling for Alzheimer's disease and dementia prevention (INSPIRATION) study aims to explore the frequency and distribution of risk factors for AD in the participants of an Alzheimer Prevention Registry in order to establish individualized risk profiles and aid the development of personalized prevention programs.MethodCross‐sectional assessment of healthy study participants aged 50 or older recruited through a local volunteer Alzheimer Prevention Registry is performed to determine the prevalence of key risk factors. This protocol includes established questionnaires and medical examination. Data is collected on demographics, medical history, family history, physical activity, diet, BMI, waist circumference, hearing loss, smoking and drinking habits, presence of depression, anxiety, stress, resilience, and loneliness. In addition, we perform neuropsychological testing and blood sampling for ApoE determination and AD‐biomarker testing. The aim is to enroll 200 individuals.ResultPreliminary results in 32 participants indicate that the three most frequent risk factors were non‐adherence to recommended diets (i.e. Mediterranean diet) in 84.4% of the subjects, obesity in 68.8% with a mean BMI of 27.6 kg/m2 (22.3‐41.6kg/m2, min./max.), and sleep problems in 50% of the subjects. The full set of assessed risk factor will be presentedConclusionThe INSPIRATION study aims to understand the prevalence of modifiable AD risk factors, in order develop a tool box of interventions for personalized strategies to prevent AD in a population, which is particularly interesting in dementia prevention.
Plasma neurofilament light chain (NfL) relates to preclinical changes in cognition, structural white matter integrity and markers of cerebral small‐vessel disease: A population‐based study
Authors: van Arendonk Joyce , Wolters Frank J. , Neitzel Julia , Vinke Elisabeth J. , Vernooij Meike W. , Ikram M. Arfan , Ghanbari Mohsen 
Published: December 2021

AbstractBackgroundNeurofilament light chain (NfL) is known as a promising biomarker for risk stratification and disease monitoring of dementia due to Alzheimer’s disease, but the underlying pathophysiological substrates remain largely elusive. Moreover, it is uncertain whether NfL levels are able to capture changes in cognitive performance prior to the onset of clinical cognitive decline. We studied the relation of plasma NfL with cognition and structural brain imaging markers in a general population without dementia.MethodPlasma level of NfL was measured using the Simoa NF‐light™ assay in 4,207 dementia‐free participants of the population‐based Rotterdam Study cohort (mean age 71.6 years, 57% women). Participants underwent repeated cognitive assessment, and a subset of 970 had brain MRI. We used linear and logistic regression (cross‐sectional) and mixed‐effects models (longitudinal) to determine the association of plasma NfL with (changes in) cognition and brain tissue volumetry, white matter integrity and markers of cerebral small‐vessel disease (lacunes, white matter hyperintensities and microbleeds).ResultAt baseline, higher plasma NfL level was significantly associated with a worse cognitive performance (g‐factor: β=‐0.06 95%CI ‐0.12;0), and more specifically with lower test scores on the Stroop 3 test (β=‐0.07 95%CI ‐0.12;‐0.01), and Perdue Pegboard (β=‐0.12 95%CI ‐0.18;‐0.06). Similarly, among 2,850 participants with repeated cognitive assessment, baseline NfL level was significantly associated with a stronger decline in cognition (g‐factor (β=‐0.02 95%CI ‐0.04;0), driven by faster decline on Stroop 1 & 2 tests (β=‐0.03 95% ‐0.04;‐0.01, β=‐0.03 95%CI ‐0.05;‐0.02, Figure 1). In participants with brain MRI, NfL level was significantly associated at baseline with larger volumes of white matter hyperintensities (β= 0.12 95%CI 0.04;0.20), more lacunar infarcts (OR= 1.69 95%CI 1.20;2.39), and worse fractional anisotropy (β=‐0.10 95%CI ‐0.18;‐0.02) and mean diffusivity (β=0.09 95%CI 0.02;0.16), but not with grey matter volumes. Plasma NfL level was not significantly related to progression of structural brain changes over time (n=738).ConclusionIn this large community‐dwelling population, higher plasma NfL levels are associated with accelerated cognitive decline and larger burden of white matter pathology. These findings suggest NfL as a predominant biomarker of axonal rather than neuronal damage in monitoring of disease progression and treatment effects.
Association between SCD‐Plus features and GDS factors in subjective cognitive decline and healthy controls in the studies DELCODE and SILCODE
Authors: Hu Xiaochen , Chen Ji , Jiang Xueyan , Daamen Marcel , Wang Xiaoqi , Lee Hwee Ling , Spottke Annika , Düzel Emrah , Peters Oliver , Buerger Katharina , Teipel Stefan J. , Laske Christoph , Boecker Henning , Wagner Michael , Han Ying , Jessen Frank 
Published: December 2021

AbstractBackgroundA previous study showed a subjective cognitive decline (SCD) related factorial score derived from the geriatric depression scale (GDS, 30 items) to predict cognitive decline within a group of healthy elderlies in interaction with amyloid status[1]. On the other hand, several features associated with SCD (SCD plus), including subjective decline in the memory domain, concerns about cognitive decline, onset within five years and over 60 years old, and cognitive performance worse than other people, have been proposed to increase the likelihood of preclinical AD in subjects with SCD[2]. Here, we test the association between SCD plus features and GDS factorial scores in two independent cohorts from Germany and China.MethodThe 15‐items GDS(GDS15) and the SCD plus score, which was assessed with the SCD‐interview[3] and which summarizes SCD plus features, were obtained from two cohorts, the DZNE‐Longitudinal Cognitive Impairment and Dementia Study (DELCODE, 230HC/361SCD), and the Sino Longitudinal Cognitive Impairment and Dementia Study(SILCODE, 99HC/135SCD). Non‐negative matrix factorization[4, 5] was applied to the GDS items from the two cohorts separately with the number of factors ranging from 2 to 9. The optimal number of factors, in terms of stability and generalizability, was identified by using cross‐validation in 5.000 split‐half analyses in each cohort. Partial correlations between SCD plus scores and individual loadings on each factor derived from the optimal factor structure were calculated, controlling for age, sex, education years, and the loadings on other factors.ResultFor both cohorts, the three‐factorial‐solution revealed the best generalizability (lowest out‐of‐sample increased reconstruction error of individual GDS scores), as well as good stability of item‐to‐factor assignment. Partial correlations revealed significant association of SCD plus score with two factors in the DELCODE cohort (positive mood:r=‐0.20,p=1x10‐6;cognition/anxiety:r=0.41,p=8.1x10‐25), and with two factors in the SILCODE cohort (positive mood:r=‐0.18,p=0.007; memory problem:r=0.51,p=2.6 x 10‐16)(figure 1).ConclusionThe present work corroborate the previous finding [1] that a SCD related factor can be derived from GDS. Furthermore, we demonstrated that the individual loadings on this factor are strongly associated with SCD plus features in two independent cohorts. Interestingly, the item assigned to the SCD related factor are different between two cohorts.
Gamma phase synchronization during olfactory stimulation as a marker for Alzheimer’s disease
Authors: Afzal Arshia , Sedghizadeh Mohammad Javad , Aghajan Hamid , Vahabi Zahra 
Published: December 2021

AbstractBackgroundAltered gamma oscillations have been observed in patients of Alzheimer’s disease (AD). A large number of studies have linked the quality of gamma oscillations in the frontal cortex to the performance of memory retrieval tasks. Synchronization of gamma oscillations has a strong correlation with cognitive functions (Fell et al., Nature Reviews Neuroscience 2011), and deficit in gamma synchronization in the frontal cortex has been reported as a marker for AD (Sedghizadeh et al., PLOS One 2020). In this study, we examine the phase synchronization of gamma oscillations in the EEG data recorded from the frontal cortex during olfactory stimulation as a marker for AD.MethodTwenty‐four elderly participants (13 Normal and 11 mild AD patients) participated in this study. The cognitive status of the participants was quantified using the MMSE test. Then, each participant underwent an olfactory stimulation session consisting of 120 trials of 2s stimuli presentation with a random selection of two odors (lemon as the frequent and rose as the rare odor) followed by 8s of rest. EEG data were simultaneously recorded and pre‐processed for artifact and noise removal and trial averaging. To analyze gamma band synchronization, the phase‐locking value (PLV) for lower gamma oscillations (35‐45Hz) was calculated between the Fz and Cz electrodes. Fig. 1 illustrates the measurement and processing flow.ResultOur study shows that the PLV is significantly higher for normal participants compared to AD patients (Fig. 2). Also, the phase difference between the Fz and Cz electrodes in the lower gamma band remains unchanged across trials for normal participants while it widely varies between ‐180 and 180 degrees for AD patients (Fig. 3).ConclusionThis study shows that there is a significant difference between normal participants and AD patients in terms of the synchronization of gamma oscillations in the frontal cortex in response to olfactory stimulation. These results suggest that the PLV between the Fz and Cz electrodes under olfactory stimulation can be used as a marker for AD diagnosis.