bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroimaging biomarkers in prodromal DLB
Authors: Kantarci Kejal 
Published: December 2020

AbstractBackgroundPatients with dementia with Lewy bodies (DLB) are characterized by hypometabolism in the parieto‐occipital cortex and the cingulate island sign on F18‐fluorodeoxyglucose (FDG) PET, lower medial temporal F18‐Flortaucipir uptake on tau PET, and lower volumes of the basal forebrain gray matter nuclei on MRI. Whether this pattern of imaging findings is present as early as the prodromal stage of DLB is unknown. We investigated the pattern of hypometabolism, atrophy, and Flortaucipir uptake in patients with mild cognitive impairment (MCI) who progressed to DLB and compared them to MCI patients who progressed to Alzheimer’s disease dementia (ADdem).MethodPatients with MCI who underwent FDG PET (n=17), Flortaucipir PET (n=9) and MRI (n=28) at baseline and progressed to probable DLB were included. We also included a cognitively unimpaired cohort of controls and MCI patients who progressed to probable ADdem (MCI‐AD) for comparison. Voxel‐base analysis on SPM12 and region‐based analysis were performed to compare the clinical groups.ResultPatients with MCI‐DLB had profound hypometabolism in the parieto‐occipital region extending into the temporal lobes, substantia nigra and thalamus. When compared to MCI‐AD, the hippocampal and posterior cingulate metabolism were relatively preserved in patients with MCI‐DLB, accompanied by greater hypometabolism in the substantia nigra in MCI‐DLB than MCI‐AD. MCI‐DLB patients were also characterized by greater atrophy in the substantia innominata (nucleus basalis of Meynert and the diagonal band) on MRI. F‐18 Flortaucipir uptake in MCI‐DLB was comparable to the control group, but significantly lower than MCI‐AD particularly in the medial temporal lobes.ConclusionImaging biomarkers can identify neurodegenerative changes associated with the prodromal phase of DLB. Prodromal DLB patients are characterized by greater atrophy in basal forebrain nuclei, suggesting that the degeneration of the cholinergic system occur as early as the prodromal stage in DLB. Preservation of medial temporal metabolism, the cingulate island sign, and substantia nigra hypometabolism on FDG PET and lower medial temporal F18‐ Flortaucipir uptake can be used to distinguish prodromal DLB and prodromal ADdem.
Assessment of the contribution of common genetic variants associated with Alzheimer’s disease on neuropathological burden and clinical characteristics in the Brains for Dementia Research cohort
Authors: Hannon Eilis , Brookes Keeley J. , Shireby Gemma , Attems Johannes , Sims Rebecca , Cairns Nigel J. , Morgan Kevin , Thomas Alan J. , Francis Paul T. , Mill Jonathan 
Published: December 2020

AbstractBackgroundIn addition to the well‐established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer’s disease (AD). Individually these variants confer only a small increase on an individual’s overall risk; however, combined into a polygenic risk score (PRS), they represent a powerful tool in genetic epidemiology for the investigation of correlates of high genetic risk. We investigated the clinical and neuropathological outcomes associated with high PRS for AD in the Brains for Dementia Research (BDR) cohort.Method693 individuals in the BDR cohort with high quality genetic data and neuropathology measurements, including staging assessments (Braak and Thal) and established diagnostic criteria were included in this study. PRS were calculated for each individual as the number of genetic risk alleles, weighted by the log odds ratio, using the results of the largest available GWAS of AD. Statistical analysis was performed using regression models whilst controlling for age at death, sex and brain bank.ResultWe report statistically significant associations between APOE genotype and Braak neurofibrillary tangle stage, a measure of tauopathy, and Thal stage, a measure of Aβ plaque propagation. We also found significant associations between AD PRS and multiple measures of neuropathology (Braak stage, Thal stage, Lewy body stage, and severe cerebral amyloid angiopathy). In order to determine if APOE and AD PRS represent independent predictors of tauopathy (Braak stage) and b‐amyloidosis (Thal stage), we performed a joint analysis finding that APOE and PRS combine in an additive manner to influence both measures of neuropathology.ConclusionThe results from this study characterise how genetic risk for AD influence both the clinical and pathological features of dementia and increases our understanding of the interaction between APOE status and other genetic risk factors.
Analysis of structural and functional connectivity MRI biomarkers in Alzheimer’s disease
Authors: Smeets Dirk , de Barros Nuno Pedrosa , Billiet Thibo , Sima Diana M. , Mohtasib Rafat , Alghamdi Jaman , Jobbeir Aman , Masawi Ahmed , Ribbens Annemie , Van Hecke Wim 
Published: December 2020

AbstractBackgroundMRI allows detecting functional and structural connectivity changes in Alzheimer’s disease (AD). However, the relative importance of the corresponding MRI‐biomarkers is not fully understood. Moreover, several of these connectivity changes are not only driven by AD but also by healthy aging, which can limit the use of these biomarkers. Therefore, we looked at how 31‐different MRI biomarkers change due to aging and the presence of AD. Furthermore, we trained a set of machine‐learning‐models to distinguish AD from control subjects. The models were used to rank the features in terms of classification‐performance and analyze the impact of including age.Method20 AD patients and 20 age and gender‐matched healthy controls underwent MRI scanning (3T GE), including T1‐weighted, diffusion‐MRI, and resting‐state‐fMRI (rsfMRI). Whole‐brain (WB), white matter (WM), gray matter (GM), cortical GM and left and right hippocampi volumes were measured using T1‐images and icobrain. rsfMRI between regions of the default mode network was assessed using group independent component analysis. Median diffusivity and kurtosis values in GM and WM were determined. T‐tests between groups and ANOVA analysis using a Generalized‐Linear‐Model that included age and AD‐status as covariates were conducted for each feature. For assessing the ability of each feature to separate AD subjects from controls, a Support‐Vector‐Machine (SVM) model was trained using each feature separately and each feature with age. Performance was measured using 10‐fold cross‐validation.ResultFigure 1 shows the table with the ANOVA results. Generally, rsfMRI features showed only a significant association with disease‐status, whereas structural and diffusion‐derived features showed both an association with age and disease‐status. Figure 2 shows the classification performance for the different SVM models. Regarding classification performance, the models trained with the total volume of the hippocampus achieved the highest performance (accuracy:77%, sensitivity:64%, specificity:89%). Despite several of the features changing with both age and AD‐status, the inclusion of age in the SVM‐models didn’t provide an advantage in classification performance.ConclusionMultiple MRI‐biomarkers are able to detect structural and functional connectivity changes associated with AD. From those, the hippocampi volumes are the ones that better distinguish AD patients from cognitively‐healthy subjects.
Correlation between regional brain atrophy, cognitive function, adipose tissue and CSF biomarkers in mild cognitive impairment
Authors: Fernández Miguel Ángel Rivas , Lojo‐Seoane Cristina , Galdo‐Álvarez Santiago , Aldrey‐Vázquez Jose M. , Vieites Ana Nieto , Fernández Alba , Pías‐Peleteiro Juan M. , Ferreiro‐Caneiro Uxia , Domínguez‐Vivero Clara , Mallo Sabela C. , Gil Luis , Pereiro Arturo X. 
Published: December 2020

AbstractBackgroundCharacterization of mild cognitive impairment (MCI) for clinical and research purposes involves identification of biological and neuropsychological markers in order to predict possible progression to dementia. The main aim of this work was to analyze the correlation of anthropometric measurements and plasmatic levels of leptin, testosterone and estrogens with cognitive, CSF and MRI regional atrophy markers in a sample of MCI participants.MethodsEighty‐one patients from the Compostela Aging Study diagnosed as MCI according to the Petersen criteria (Petersen, 2004; Albert et al., 2011) underwent neuropsychological assessment (CAMCOG‐R memory, CVLT short and long delayed free recall, subjective memory complains), CSF (Aβ42, t‐Tau and p‐Tau) and plasmatic analyses as well as an MRI study (parahippocampal and entorhinal cortex thickness measurements) (Table 1). Spearman’s correlation was used to evaluate the relationship between anthropometric measurements and blood test results with memory scores, CSF and MRI regional atrophy markers.ResultsEpisodic memory scores correlated with CSF measurements (Aβ42, t‐Tau, p‐Tau) and parahippocampal and entorhinal cortical thickness (right and left) (Table 2). BMI, suprailiac, pectoral and subscapular skinfolds, circumference of waist, hip, arm and calf were negatively correlated with t‐Tau and p‐Tau levels. BMI, triccipital, thigh and pectoral skin folds as well as calf circumference were positively correlated with parahippocampal and entorhinal cortical thickness. Suprailiac, triccipital and thigh skin folds were positively correlated with episodic memory scores. Leptin plasma levels showed a negative correlation with CSF biomarkers (t‐Tau and p‐Tau) and a positive correlation with parahippocampal cortex thickness. Testosterone and estradiol levels showed a negative correlation with scores on memory tests and enthorhinal cortical thickness.ConclusionsOur findings suggest that body composition is associated with episodic memory function, CSF biomarkers and cortical atrophy in patients with MCI. Leptin levels and sexual hormones may play a role in this association. These results point to a role of fat tissue and its regulating mechanisms in AD pathology and progression from MCI to dementia.
Who am I with my Lewy bodies? A self‐concept study
Authors: Tisserand Alice , Noblet Vincent , Botzung Anne , Blanc Frédéric , Philippi Nathalie 
Published: December 2020

AbstractBackgroundNeurodegenerative diseases are marked by changes in personal identity, including the self‐concept (SC), which refers to a collection of knowledge about oneself, made up of personal semantic information. Modifications of the Self have been extensively investigated in Alzheimer's disease (AD), whereas it has never been studied in dementia with Lewy bodies (DLB). Yet, key regions for Self‐processing such as the medial prefrontal, the anterior cingulate and the insular cortices, are damaged early in the course of DLB. Thus, the purpose of this study was to investigate the SC integrity and to explore its neuroanatomical correlates in early DLB as compared to AD and normal ageing.MethodTwenty prodromal to mild DLB patients were compared to twenty‐one prodromal to mild AD patients, and to twenty‐one healthy control subjects, matched in terms of age and educational level. For all participants, SC was assessed using the Twenty Statements Test (TST) during which the subjects were asked to produce up to twenty affirmations answering the question: who am I? Behavioral performance was compared between the groups. 3D MRI images were acquired for DLB patients and correlational analyses were performed using voxel‐based morphometry (VBM).ResultBehavioral results obtained in the TST showed significantly decreased performances in both DLB and AD groups compared to healthy control subjects (p<0.001). Moreover, DLB patients tended to produce less Self‐affirmations than AD patients. Additionally, correlational analyses between behavioral scores and neuroimaging data in the DLB group revealed positive correlations between the number of produced Self‐affirmations and grey matter volume in the medial and orbitofrontal prefrontal cortices and in the lateral temporal cortex, among other regions (central sulcus, hippocampus, cerebellum).ConclusionOur behavioral results confirmed that SC is affected from the early stage in both DLB and AD, and tends to be even more deteriorated in DLB. Interestingly, VBM analyses revealed that decreased performance in DLB patients was related to focal atrophy in regions such as medial prefrontal and lateral temporal cortices, which are central in the networks of Self‐processing and semantic memory, respectively.
Characterising vascular cognitive impairment compared to cognitively healthy ageing with respect to reaction time, the intra‐individual variability of RT, and error production, practice effects and the task used in their measurement
Authors: Richards Emma V. , Bayer Antony , Tales Andrea 
Published: December 2020

AbstractBackgroundTo improve the characterisation and the understanding of VCI by examining reaction time (RT), the intra individual variability of RT (IIV), errors, practice, the effects of processing load (e.g. the influence of distracting information) and the effects of hesitancy in cognitively healthy (CH) ageing compared to patients with Subcortical Ischaemic VCI (SIVCI). In addition, the potential influence of the task used to measure these factors upon these results was investigated. The DSM5 requires a measure of brain processing speed to aid in the diagnosis of vascular dementia, but there is no indication of which test to use.MethodTasks comprised of the Trail Making Task (TMT), a clinical test used to measure RT, a visual search task, commonly used in research to measure RT, IIV, errors the effect of distracting information and practice, and an iPad based test ‘iReact’ used to measure hesitancy in response to a stimuli, in the same group of participants. Finally, for the SIVCI group, task performance was investigated with respect to the level of CT or MRI‐visible white matter disease.ResultResults were test dependent, for the TMT results revealed poor completion rates, with 75% of VCI being unable to complete, results also differed depending on analysis used. The visual search task revealed a greater range of results; RT, IIV, errors production and the effect of distracters were significantly worse for those with SVCI compared to CH adults. iReact test results revealed that SIVCI were significantly more hesitant and varied in their response than CH adults. White matter disease was also identified as a poor marker of cognitive function, possibly due to silent lesions, and that RT related function is a better indicator of brain function.ConclusionSubcortical Ischaemic Vascular Cognitive Impairment is characterised by slowed RT, Increased IIV, detrimental effect of distracting information, raised error production, lack of positive practice effects on IIV, very slow response initiation and disproportionately high IIV in response initiation.
Quantitative thresholds for 18F‐florbetaben PET for the detection of low amyloid load
Authors: Roé‐Vellvé Núria , Bullich Santiago , Marquie Marta , Barthel Henryk , Villemagne Victor LL , Sanabria Angela , Tartari Juan Pablo , Sotolongo‐Grau Oscar , Dore Vincent , Koglin Norman , Mueller Andre , Perrotin Audrey , Jovalekic Aleksandar , de Santi Susan , Tarraga Lluis , Stephens Andrew W , Rowe Christopher C , Sabri Osama , Seibyl John , Boada Mercè 
Published: December 2020

AbstractBackgroundA pathology‐proven cutoff for NeuraCeq (18F‐florbetaben) was previously developed in end‐of‐life cases to discriminate Alzheimer’s disease (AD) patients from elderly Aβ‐negative non‐demented controls (NDC). However, these cutoffs could be of limited use in early stages of AD. Here, we developed and validated 18F‐florbetaben cutoffs to detect low Aβ deposition and established amyloid pathology.MethodThe low Aβ deposition threshold was derived from a sample of young healthy controls (YHC) (n=70, 27.6±5.1 y), as 2 standard deviations above the mean. The established pathology cutoff was derived using ROC curve analysis on a sample of visually determined Aβ‐negative NDC (n=62, 67.8±6.8 y) and Aβ‐positive AD dementia patients (n=62, 70.6±8.0 y). Validation was based on longitudinal samples: (1) subjective cognitive decline (SCD) volunteers (n=166; 64.9±7.2 y) and (2) mild cognitively impaired (MCI) subjects (n=45, 72.7 ± 6.5 y). The standard centiloid (CL)methodology was applied for quantification.ResultThe low Aβ‐deposition detection cutoff was 13.5 CL, and the threshold for established Aβ pathology was 35.7 CL. In the validation samples, the rate of Aβ accumulation in the “low amyloid load” interval (13.5‐35.7 CL) was significantly different from zero (p<0.05), (2.1±2.1 %/year (SCD), 2.6±1.5 %/year (MCI)), which was also observed for “established Aβ deposition” (>35.7 CL) (3.4±3.2 %/y (SCD), 1.4±1.8 %/y (MCI), (p<0.05)). The accumulation rate for Aβ‐negative subjects (<13.5 CL) was not significantly different from zero (‐0.1±1.1 %/year (SCD), 0.1±1.6 %/year (MCI)).ConclusionAn interval between 13.5 and 35.7 CL is optimal for the detection of early Aβ deposition and to identify subjects that are likely accumulating Aβ. Further validation tests using additional samples are ongoing.
Changes in anterior temporal and posterior medial hippocampal network connectivity in Alzheimer’s disease
Authors: Dautricourt Sophie , de Flores Robin , Landeau Brigitte , Poisnel Géraldine , Vanhoutte Matthieu , Delcroix Nicolas , Vivien Denis , De la Sayette Vincent , Chetelat Gael 
Published: December 2020

AbstractBackgroundHippocampal connectivity is affected early in Alzheimer’s disease and plays a crucial role in episodic memory dysfunction. Different hippocampal subnetworks have been identified, namely the anterior temporal (AT) and the posterior medial (PM) networks that are specifically related to separate subregions of the medial temporal lobe (MTL) thought to be differentially affected in AD. The aim of this study was to assess the specific connectivity of these two networks and its changes in Alzheimer’s disease, using both a cross‐sectional and a longitudinal approach.MethodFifty‐three cognitively impaired patients on the Alzheimer’s continuum with mild cognitive impairment or dementia, all amyloid‐β (Aβ)‐positive, and 68 Aβ‐negative cognitively unimpaired elderly controls were included. They underwent structural T1‐MRI and resting‐state functional MRI (fMRI) scans at baseline and at 18‐month follow‐up as well for 30 patients. Seed‐based analyses were performed, using individual automatic segmentation of MTL subregions as seeds, to assess the functional connectivity within the AT (from the perirhinal cortex and anterior hippocampus seeds) and the PM (from the parahippocampal cortex and posterior hippocampus seeds) networks. First, we compared the functional connectivity of the two networks within the controls to highlight their specificities. Second, we compared MTL subregion connectivity within each network between groups, and between baseline and follow‐up in the patients, to assess AD‐related changes compared to controls and over time.ResultAT and PM networks showed distinct connectivity patterns in controls (Fig. 1). Patients showed decreased connectivity between the anterior hippocampus and regions of the PM network, and increased connectivity between anterior MTL subregions, compared to controls (Fig. 2). Over the 18‐month follow‐up period, decreased connectivity was found between both the anterior and posterior hippocampus and regions of the PM network, while increased connectivity was observed between several anterior MTL subregions and regions of the AT network (Fig. 3).ConclusionAD is characterized by both decreased MTL connectivity with the PM hippocampal network and increased connectivity with the AT hippocampal network. The specific assessment of the two main hippocampal subnetworks shed light on the overall pattern of AD‐related hippocampal changes involving both connectivity default and possible compensation or erroneous hyperactivity patterns.
Mesoscopic compensations for microscopic impairments in mid‐age individuals with family history of dementia
Authors: Su Li ,   the PREVENT‐Dementia Study
Published: December 2020

AbstractBackgroundIn the PREVENT‐dementia study, we investigated multi‐level functional MRI changes in cognitively normal middle‐aged subjects. At the mesoscopic level, regional cerebral hypoperfusion is characteristic of Alzheimer’s disease (AD). At the microscopic level, AD showed a reduced BOLD activity. However, previous studies using these techniques report conflicting findings in cognitively‐normal individuals at high risk of AD.Method210 subjects between age 40‐59 underwent 3T arterial spin labelling (ASL) MRI and task MRI (tMRI). During the task, subjects made an indoor/outdoor judgment for images of scenes. After a delay of 30‐40 minutes, they identified the stimuli that were previously learnt. As a measurement of stability in neural representations, we quantified the multi‐voxel pattern similarity in parahippocampus regions between the encoding and retrieval parts of the experiment. ASL cerebral perfusion and tMRI responses were statistically compared between subjects with parental history to those without, and carriers of the Apoε4 with non‐carriers.ResultRegional hyperperfusion was found in APOE e4 carriers (left cingulate and lateral frontal and parietal regions p<.01) and in those with positive FH (left temporal and parietal regions p<.01). For the tMRI task, we found no overt impairments of memory performance. However, there was a significant change in multivoxel activation pattern in parahippocampus areas for subjects with parental history (p<.01), reflecting a failure to maintain stable memory representations between the learning and testing parts of the experiment. This effect was not seen in the subjects with APOE ε4.ConclusionThe novel findings on the implicit memory related MRI task suggest that the microscopic functional impairments may begin as early as mid‐age. The absence of APOE ε4 genotype effect on the task MRI implies that family history may include other genetic and/or environmental risk factors. Hyperperfusion in individuals at increased risk of AD may reflect a nonspecific mesoscopic functional ‘compensation’, offsetting the effects of early neural damages including the reduction in parahippocampus functions.