bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case with early onset Alzheimer’s disease with amyloid uptake not only in cerebrum but also in cerebellum
Authors: Lee Sunju , Jo Sungyang , Kim Hyung‐Ji , Lee Jae‐Hong 
Published: February 2022

AbstractBackgroundAmyloid positron emission tomography (PET) imaging is appropriate for patients with atypical presentation, unusually rapid course and very early onset of dementia. Standardized uptake value ratios (SUVr) are used for relative quantification of 18F‐florbetaben (18F‐FBB) PET scans and cerebellar cortex can be used as reference region for quantification. Previous study showed that 18F‐FBB PET demonstrated a diffuse cortical uptake and in particular an intense uptake in the basal ganglia in familial Alzheimer’s disease with presenilin‐1(PS‐1) mutation.MethodThis report describes the case of a young woman with early‐onset familial Alzheimer’s disease(EOfAD), who has atypical pattern of uptake on amyloid PET.ResultA 37‐year‐old woman with a college level educational background was brought in by her family for further evaluation of cognitive impairment, personality and behavioral changes. At age 30 years of age, the patient presented memory impairment and she had difficulty serving guests in bakery. Patient had positive family history of early onset dementia; her father, grand mother, and two sisters of grand mother. (Fig. 1 Pedigree showing autosomal dominant inheritance trait of early‐onset dementia. (nn/nn) Age at onset/age at death). She had an initial Mini‐Mental State Examination score of 22/30 (time disorientation, dyscalculia, poor delayed recall). Neuropsychological assessment showed global cerebral dysfunction and revealed dementia with psychiatric symptoms. Brain magnetic resonance imaging showed no significant abnormality. On genetic testing, homozygotes for the apolipoprotein E ε3 allele and a PS‐1 mutation (c.616G>A , p.G602S) was identified. 18F‐FBB PET revealed diffusely increased amyloid deposition including not only bilateral frontal, parietal, posterior cingulate gyrus/precuneus, anterior striatum but also bilateral cerebellar cortex. (Fig. 2 18F‐florbetaben PET, at age 37)ConclusionThis will be the first case report of EOfAD with increased bilateral cerebellar cortical uptake on 18F‐ FBB PET, we present the case to increase awareness of this unusual entity.
Progression in WMH volume is accompanied by higher gray matter loss: One‐year follow‐up MRI study in TATA Longitudinal Study on Aging Cohort of India
Authors: Tiwari Vivek , Rao Naren P. , M.L. Abhishek , Ravindranath Vijayalakshmi 
Published: February 2022

AbstractBackgroundSmall vessel disease pathologies such as white matter hyperintensity (WMH) and loss in neuroanatomical volumes with aging have been investigated across various cross‐ sectional and longitudinal‐aging studies in different parts of world. However, it is yet not extensively investigated whether the changes in WMH kinetics over the period impacts the neuroanatomical health? Here, we have measured changes in WMH and neuroanatomic‐volumes, in an ongoing longitudinal study on aging in India called TATA longitudinal study on aging (TLSA), at the baseline and one‐year‐follow‐up visit. The TLSA‐study is a prospective, community‐based, cohort study that comprises of cognitively healthy, educated, and multilingual individuals of both genders aged ≥45 years. The subjects are recruited from urban‐Bangalore, a large metropolitan city in southern India.MethodMRI measurements were conducted on 3T whole‐body‐scanner. MRI study performed close to the first clinical and cognitive‐examination is termed as baseline visit (V0), while MRI close to one‐year follow‐up is termed as V1. T2w‐FLAIR, 3D‐MPRAGE and DWI MRI were performed at both V0‐ and V1‐visits. WMH was quantified using T2w‐FLAIR and MPRAGE‐T1w images. Anatomical volumes were determined using Freesurfer. The volumes were normalized to the total‐intracranial‐volume. Changes in WMH and anatomic volume were calculated as (Volume at V1 – Volume at V0).ResultChanges in WMH and neuroanatomic volumes were evaluated for 128‐subjects who had MRI at both the visits, V0 and V1. Quantification of change in WMH (Delta‐WMH) in the TLSA‐subjects revealed that 65% of the subjects showed progression in WMH‐volume while another 35% did not show WMH‐progression. This indicated that there is a subset of cohorts that showed progression in WMH volume (+0.5‐7.9 ml) while another subset of subjects had no change in WMH over the period. Segmentation of neuroanatomical‐volume showed that the subset of the cohort that showed WNH‐progression over the one‐year period had significantly larger reduction in gray‐matter and increase in CSF volume at V1 compared to another subset that did not had changes in WMH.ConclusionProgression in WMH may be associated with increased vascular insult to the brain resulting in substantial gray‐matter loss and ventricular increase. Increase in WMH volume may fasten the neuroanatomic deteriorations with aging.
The experiences of apathy in people with dementia and mild cognitive impairment and their carers: A qualitative interview study
Authors: Burgon Clare , Goldberg Sarah , van der Wardt Veronika , Harwood Rowan H 
Published: February 2022

AbstractBackgroundApathy, defined as reduced goal‐directed activity, social engagement and emotion, is highly prevalent in dementia and Mild Cognitive Impairment (MCI), and has important consequences for the individuals that experience it and those who care for them. However, the lived experiences of this population is not well understood. This study aimed to explore how people with dementia and MCI and their carers experience apathy.MethodPeople with early dementia and MCI living in four geographical areas of England were invited to take part in a qualitative interview. All participants had capacity to give informed consent. In‐depth semi‐structured interviews were conducted with fourteen people with dementia or MCI and carer dyads, and two participants without a carer present. Patient’s mean age was 76 years, Montreal Cognitive Assessment score was 20, and five were female. Interviews, conducted in the participant’s homes, lasted between 38 and 115 minutes, were audio‐recorded and transcribed verbatim. Reflexive thematic analysis was used to analyse the data.ResultFindings were organised into two connected themes: ‘The struggle of everyday life is not worth it’ and ‘Threatened identity: changing sense of self and place in the world’. Participants’ everyday lives required more effort and were a “struggle” due to cognitive and physical impairments. This could make the effort to engage, act, and maintain interest not worth it, resulting in apparent apathy. Motivation to stay engaged despite difficulty was influenced by the accessibility of opportunities, and support from others. Participants views of their (past) autonomous and competent self were challenged by the changes they experienced. Participants sometimes focused on their present capabilities, and did what they were still able, whilst others found changes difficult to accept and withdrew from situations which challenged their sense of self.ConclusionApathy is experienced as a response to the everyday difficulties participants faced, which could be exacerbated by lack of support and opportunities. This is in contrast to the popular view of apathy as a symptom of neurodegenerative changes that occur in dementia. Our findings echo those of qualitative research in people with Parkinson’s Disease (Simpson et al., 2014).
Dementia with Lewy bodies subtypes identified by cluster analysis on structural MRI
Authors: Inguanzo Anna , Poulakis Konstantinos , Mohanty Rosaleena , Schwarz Christopher G. , Przybelski Scott A. , Lemstra Afina W. , van de Beek Marleen , van der Flier Wiesje M , Barkhof Frederik , Blanc Frédéric , de Sousa Paulo Loureiro , Philippi Nathalie , Cretin Benjamin , Demuynck Catherine , Nedelska Zuzana , Hort Jakub , Segura Barbara , Junqué Carme , Oppedal Ketil , Aarsland Dag , Westman Eric , Kantarci Kejal , Ferreira Daniel 
Published: February 2022

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder that presents with a variety of clinical symptoms. Part of the clinical heterogeneity within DLB has been related to the atrophy/sparing of the hippocampus. We extended that previous research by investigating whether different atrophy patterns exist in DLB, beyond and above the atrophy/sparing of the hippocampus, and whether those patterns contribute to the clinical heterogeneity in DLB. We aimed to identify DLB atrophy subtypes using a hypothesis‐free data‐driven clustering approach based on regional gray matter (GM) volumes and characterize the resulting subtypes across key measures.MethodWe included data from three centers of the European DLB consortium. A high‐resolution 3D T1‐weigthed magnetization prepared rapid gradient echo (MPRAGE) sequence was acquired for 97 DLB patients. Eighty‐four cortical regions and 12 subcortical regions from Mayo Clinic Adult Lifespan Template (https://www.nitrc.org/projects/mcalt/) atlases were obtained. Clusters of DLB patients were then determined using the random forest method. Between‐group differences in key demographic, clinical, MRI volumes and cerebrospinal fluid biomarkers (CSF) (amyloid‐beta, phosphorylated‐tau) were performed for clusters characterization.ResultWe identified three subtypes of DLB patients, with distinct patterns of GM volumes and differences in several clinical and demographic measures. Cluster 1 (C1) included 32 DLB patients (33%), cluster 2 (C2) included 29 DLB patients (30%), and cluster 3 (C3) included 36 DLB patients (37%). The clusters differed in age, with C1 being significantly older (72±8.6) than C3 (66±9.5) (F=3.93, p=0.02). C1 was characterized by lower volumes in fronto‐temporal regions and had a higher frequency of visual hallucinations (68%, vs. C2 35%). C2 showed lower volumes in occipital regions. C3 had higher GM volumes overall compared with the other two clusters and presented with a higher frequency of cognitive fluctuations (91%, vs. C1 67%). There were no differences between groups in CSF biomarkers. These results were independent of cluster differences in age and global GM volume.ConclusionThere are distinct patterns of brain atrophy in patients with DLB. These patterns seem to differentially contribute to the frequencies of visual hallucinations and cognitive fluctuations, independently of differences in age and global GM volume across subtypes.
The influence of known pathogenic gene mutation and ApoEε4 on neuropsychological evaluation and imaging markers in preclinical stage of familial Alzheimer’s disease
Authors: Quan Meina , Jia Longfei , Tang Yi , Wang Qi , Zhao Tan , Qiu Qiongqiong , Yang Jianwei , Wang Wei , Qin Qi , Wang Yan , Li Wenwen , Xu Hui , Gong Min , Li Fangyu , Li Tingting , Cao Shuman , Li Xinyue , Wang Qigeng , Lu Jie , Jia Jianping 
Published: February 2022

AbstractBackgroundIn the preclinical stage of familial Alzheimer's disease (FAD), there have been changes in multi‐dimensional indicators, such as pathology, neuropsychology and imaging. This study explored the effects of known pathogenic gene mutation and ApoE on neuropsychology and imaging markers before the appearance of FAD symptoms.Method102 cases of asymptomatic mutation non‐carriers (26 cases of ApoEε4) and 38 cases of asymptomatic mutation carriers (17 APP, 21 PS1) in FAD families were assessed by a series of neuropsychological scales, including mini mental state scale (MMSE), auditory verbal learning test (AVLT), etc. MRI images were collected. The volume of representative brain regions was obtained, including subregions of striatum, hippocampus, rostral middle frontal gyrus (rMFG), and posterior cingulate cortex (PCC). Diffusion indices and functional connectivity (FC) of neural pathways (striatum subregions to rMFG, hippocampus to PCC) were also obtained. The neuropsychological scores and imaging indexes were compared between groups, and the imaging indexes with group differences were further correlated with neuropsychological scores.ResultCompared with asymptomatic mutation non‐carriers, APP group showed a trend increase in delayed recall score in AVLT (P = 0.08), significantly increased cued recall score, and increased radial diffusivity (RD) of bilateral caudate‐rMFG pathway (fig 1, P's < 0.05). In asymptomatic mutation non‐carriers, compared with APOEε4 non‐carriers, APOEε4 carriers showed increased right hippocampal volume, decreased fractional anisotropy (FA) of bilateral hippocampus‐PCC pathway, and increased FC of left caudate‐rMFG pathway (fig 2, P's < 0.05). The RD of right caudate‐rMFG pathway in PS1 group was positively correlated with MMSE total score (r = 0.749). The FC of left caudate‐rMFG pathway was negatively correlated with MMSE total score (fig 3, r = ‐ 0.623, P’s < 0.05).ConclusionThere are neuropsychological and imaging changes in the early stage of FAD, which are affected by the known pathogenic gene mutation and ApoEε4. APP mutation affected memory domain in cognitive function and the structural connectivity of fronto‐striatal pathway. ApoEε4 mainly affected the structural connectivity of hippocampus‐PCC pathway. The hippocampal volume and the functional connectivity of fronto‐striatal pathway increased compensatively. The overall cognitive function is differently related to the structural and functional connectivity of fronto‐striatal pathway in APP, PS1 and ApoEε4.
How animacy processing is affected in early stages of AD
Authors: Marefat Haniye , Ebrahiminia Fatemeh , Khanbagi Mahdiyeh , Karimi Hamed , Modarres Mohammad Hadi , Kalafatis Chris , Vahabi Zahra , Khaligh‐Razavi Seyed‐Mahdi 
Published: February 2022

AbstractBackgroundPrevious studies have shown that cognitive impairment in early stages of Alzheimer’s disease (AD) is not limited to memory; other cognitive domains are also disrupted including impairment in visual processing (Boucart, Bubbico et al. 2014). Additionally, it is shown that in healthy human subjects, images are categorized by their animacy status (i.e. animate vs. inanimate) in the higher‐level visual areas (Kriegeskorte, Mur et al. 2008). Here we used fMRI to investigate the spatial patterns of animacy processing in the brain of patients with mild cognitive impairment (MCI)/AD in comparison to healthy controls(HC).MethodWe recruited 20 HCs, 15 MCIs and 10 mild‐ADs. Participants completed the Integrated Cognitive Assessment (ICA) test (Khaligh‐Razavi, Habibi et al. 2019) in the fMRI scanner. ICA is a rapid visual‐categorization task, in which participants indicate whether a presented image contains an animal or not, as fast and accurately as they can. In addition to the conventional univariate analysis –looking at the mean brain responses– we used multivariate‐pattern‐analysis (MVPA) to investigate differences in patterns of brain activity between the three groups. In MVPA, we trained a linear classifier for each brain area, to do animal/non‐animal categorization based on the patterns of brain responses to the images.ResultIn some of the key brain regions, such as R‐parahippocampus and R‐fusiform, overlapping with early tau‐pathology (Braak, Alafuzoff et al. 2006), both HC and MCI showed a significantly higher level of mean brain activity in response to all images compared to the AD group (p‐value<0.0001). Additionally, looking at the patterns of brain activity in the L‐fusiform, HC and MCI could be discriminated based on their MVPA responses(p‐value<0.0015), while there was no univariate difference between the two groups.ConclusionWe demonstrated HC and MCI/AD can be differentiated not only based on univariate analysis, but also by multivariate measures, i.e. patterns of brain responses to images. Moreover, we showed that the rapid visual categorization task used in this study could engage key brain areas affected by tau pathology in early stages of the disease. This highlights the potential application of such task for earlier detection of the disease, ideally before the onset of memory symptoms.
Subtyping mild cognitive impairment based on imaging and CSF biomarker levels
Authors: Dadar Mahsa , Shafiee Neda , Collins Louis , Camicioli Richard , Duchesne Simon 
Published: February 2022

AbstractBackgroundIndividuals with mild cognitive impairment (MCI) have variable clinical outcomes, with a proportion converting to dementia in a short follow‐up period. Subtyping MCI subjects based on biomarker levels can provide additional insights on why some individuals progress faster, aiding clinical treatment strategy and facilitating cohort enrichment for clinical trials.MethodData included 562 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project with baseline MRI, CSF amyloid beta (Aβ), t‐tau, and p‐tau data and a minimum of one‐year follow‐up information on clinical diagnosis. White matter hyperintensities (WMHs) were segmented using a previously validated random forests classifier (Dadar et al. 2017). SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer’s‐disease‐like atrophy patterns in the hippocampi (HC) and entorhinal cortex (EC) (Coupé et al. 2019). CSF Aβ, p‐tau and t‐tau levels were obtained from project files. Agglomerative hierarchical clustering as used to cluster the data based on baseline age, education, APOE4 status, CSF Aβ, p‐tau and t‐tau levels, WMH load, and HC and EC grading scores. We then investigated differences in baseline ADAS13 cognitive scores as well as rate of conversion to dementia between different subtypes.ResultFigure 1 shows the clustering dendrogram, splitting the data into three subtypes of 152, 200, and 210 participants, respectively. Figure 2 compares biomarker values across subtypes. Baseline ADAS13 scores and conversion rates were significantly different across all subtypes (p<0.0001). Subtype 1 had the oldest subjects with largest WMH loads (p<0.0001), with a conversion rate of 30.2%. Subtype 2 had the highest conversion rate (70.0%), with significantly lower CSF Aβ and EC grading scores, and higher CSF p‐tau and t‐tau values (p<0.0001). Subtype 3 had the lowest conversion rate (15.2%), with significantly higher HC and EC grading scores and lower age and WMH loads than the other two subtypes (p<0.0001).ConclusionBiomarker‐based subtyping of MCI subjects led to three distinct groups with significantly different clinical outcomes: 1) older individuals with cerebrovascular pathology and moderate conversion rates, 2) individuals with abnormal CSF biomarker levels, hippocampal and entorhinal atrophy, and high conversion rates, and 3) younger individuals without abnormal biomarker levels and low conversion rates.
Longitudinal assessment of [18F]FDG‐PET in the TgF344‐AD rat
Authors: da Rocha Andreia Silva , Ferreira Pamela C.L. , Bellaver Bruna , Peixoto Guilherme G. Schu , Venturin Gianina Teribele , Greggio Samuel , da Costa Jaderson Costa , Souza Diogo O. , Zimmer Eduardo R. 
Published: February 2022

AbstractBackgroundThe development and characterization of biomarkers abnormalities in Alzheimer’s disease (AD) animal models is particularly important for the investigation of pathophysiological mechanisms and drug development. With this is mind, here, we aimed at characterizing the brain glucose metabolism, indexed by [18F]FDG‐microPET, of the TgF344‐AD rat, a model harboring human APP/PS1 mutations. We hypothesized early hypometabolism ‐ due to astrocyte reactivity and microglial activation ‐ followed by hypometabolism in later stages – due to neurodegeneration.MethodHemizygous TgF344‐AD rats and their sex‐matched wild type littermates (n=16) were evaluated in three time points: 3, 6 and 9 months of age. Rats underwent [18F]FDG‐microPET for brain glucose metabolism analysis (SUVr, using the pons as reference region). Locomotor activity and spatial memory were assessed using Open‐Field and and Y‐maze tests, respectively.ResultTgF344‐AD animals showed no differences in [18F]FDG‐microPET analysis in any of the ages analyzed (Figure A). On the other hand, a decline on their performance in the Y‐maze task was identified at the 9 months time point (p = 0.0132), suggesting a decline in their spatial memory at this age (Figure B). No differences were identified on the parameters analyzed in the Open Field task.ConclusionThis study is the first to investigate the in vivo brain glucose metabolism in the TgF344‐AD rat model. Our preliminary results suggest that, in comparison to age and sex‐matched littermates, this APP/PS1 rat model does not present relevant changes in the brain glucose metabolism at early stages, even in the presence of detectable cognitive decline.
The role of biomarkers in cell counting with U‐Net CNN
Authors: Miramontes Silvia , Piergies Antonia M.H. , Grinberg Lea T. , Ushizima Daniela 
Published: February 2022

AbstractBackgroundImaging methods that are non‐destructive preserve tissue integrity and lead to improved topography analysis for the study of neurodegenerative diseases like Alzheimer’s Disease (AD). Immunofluorescence (IF) staining methods facilitate such investigations by addressing a gradient of intensity variations relevant for in situ cell detection [1] and morphology quantification. This paper reports on the colocalization of proteins and cell structures from human post‐mortem tissue by evaluating IF expression by means of TBR1 and NeuN biomarkers. We compare different U‐Net‐based models by exploring image representations obtained by combining image channels with different biomarkers.MethodFrom an image dataset with 21 full‐size IF micrographs, we perform data augmentation by creating a cropping mechanism resulting in 40 to 60 image crops from each micrograph, each crop with 128x128 pixels. Later, we enhance the resulting 1,200 cropped images, and construct 3‐channel (X,Y,Z) image inputs of dimensions 128x128x3 for the U‐Net model in a two‐fold process: (I) stack all 3 channels with single‐channel IF cropped images corresponding to NeuN biomarkers (NeuN, NeuN, NeuN); (II) stack the single channel images of TBR1, NeuN, and a single image representing the maximum pixel intensities from TBR1 and NeuN images (TBR1, NeuN, max (TBR1, NeuN)). With a test‐train split of 70% ‐ 30%, and parameter tuning, we compare the two models via metrics such as neuron areas, counts, accuracy and recall.ResultThe model trained with channel stacking (II) outperforms the model trained with (I) with an accuracy and recall of 0.96 and 0.5, as opposed to 0.95 and 0.4. We also found a great variation in neuron area and counts as depicted in the images below.ConclusionWhile this is the first step in accelerating the quantification of neurons for the pathophysiology studies necessary for drug development, there is a need in establishing protocols for the generation of datasets with manual segmentation to further train our models. The inclusion of prior information about the expected neuron morphology increases the performance of our networks, and can successfully deploy a foreseen automated pipeline. [1] Ehrenberg et al. A manual multiplex immunofluorescence method for investigating neurodegenerative diseases. Journal of Neuroscience Methods,June, 2020.