Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: applied to GENFI study

2018 ◽  
Author(s):  
Claire Cury ◽  
Stanley Durrleman ◽  
David Cash ◽  
Marco Lorenzi ◽  
Jennifer M Nicholas ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Clinical Symptoms ◽  
Brain Structures ◽  
Spatiotemporal Analysis ◽  
Cortical Atrophy ◽  
Imaging Biomarkers ◽  
Mri Scans ◽  
Healthy Control ◽  
Diffeomorphic Deformation ◽  
Shape Changes

AbstractBrain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer’s disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure.In this paper we propose a spatiotemporal analysis pipeline based Large Diffeomorphic Deformation Metric Mapping (LDDMM) to detect shape changes from volumetric MRI scans. We applied our framework to a cohort of individuals with genetic variants of frontotemporal dementia and healthy controls from the Genetic FTD Initiative (GENFI) study. Our method, take full advantage of the LDDMM framework, and relies on the creation of a population specific average spatiotemporal trajectory of a relevant brain structure of interest, the thalamus in our case. The residuals from each patient data to the average spatiotemporal trajectory are then clustered and studied to assess when presymptomatic mutation carriers differ from healthy control subjects.We found statistical differences in shape in the anterior region of the thalamus at least five years before the mutation carrier subjects develop any clinical symptoms. This region of the thalamus has been shown to be predominantly connected to the frontal lobe, consistent with the pattern of cortical atrophy seen in the disease.

scholarly journals Distinct epigenetic signatures between adult-onset and late-onset depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Yamagata ◽  
Hiroyuki Ogihara ◽  
Koji Matsuo ◽  
Shusaku Uchida ◽  
Ayumi Kobayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Adult Onset ◽  
Blood Biomarkers ◽  
Major Depressive ◽  
Genome Wide ◽  
Healthy Control ◽  
Epigenetic Signatures

AbstractThe heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.

scholarly journals Shape Profile of Corpus Callosum As a Signature to Phenotype Different Dementia

2020 ◽  
Author(s):  
Sandhya Mangalore ◽  
Shiva Shanker Reddy Mukku ◽  
Sriharish Vankayalapati ◽  
Palanimuthu Thangaraju Sivakumar ◽  
Mathew Varghese
Keyword(s):  
Corpus Callosum ◽  
Frontotemporal Dementia ◽  
Corticobasal Degeneration ◽  
Lewy Body Dementia ◽  
Clinical History ◽  
The Body ◽  
Cortical Atrophy ◽  
Alzheimer Dementia ◽  
Geriatric Clinic ◽  
Cortical Regions

Abstract Background Phenotyping dementia is always a complex task for a clinician. There is a need for more practical biomarkers to aid clinicians. Objective The aim of the study is to investigate the shape profile of corpus callosum (CC) in different phenotypes of dementia. Materials and Methods Our study included patients who underwent neuroimaging in our facility as a part of clinical evaluation for dementia referred from Geriatric Clinic (2017–2018). We have analyzed the shape of CC and interpreted the finding using a seven-segment division. Results The sample included MPRAGE images of Alzheimer’ dementia (AD) (n = 24), posterior cortical atrophy- Alzheimer’ dementia (PCA-AD) (n = 7), behavioral variant of frontotemporal dementia (Bv-FTD) (n = 17), semantic variant frontotemporal dementia (Sv-FTD) (n = 11), progressive nonfluent aphasia (PNFA) (n = 4), Parkinson’s disease dementia (PDD) (n = 5), diffuse Lewy body dementia (n = 7), progressive supranuclear palsy (PSP) (n = 3), and corticobasal degeneration (CBD) (n = 3). We found in posterior dementias such as AD and PCA-AD that there was predominant atrophy of splenium of CC. In Bv-FTD, the genu and anterior half of the body of CC was atrophied, whereas in PNFA, PSP, PDD, and CBD there was atrophy of the body of CC giving a dumbbell like profile. Conclusion Our study findings were in agreement with the anatomical cortical regions involved in different phenotypes of dementia. Our preliminary study highlighted potential usefulness of CC in the clinical setting for phenotyping dementia in addition to clinical history and robust biomarkers.

scholarly journals Joint Assessment of Structural, Perfusion, and Diffusion MRI in Alzheimer's Disease and Frontotemporal Dementia

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Zhang ◽  
Norbert Schuff ◽  
Christopher Ching ◽  
Duygu Tosun ◽  
Wang Zhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Diffusion Tensor ◽  
Healthy Control ◽  
Multimodal Mri ◽  
Imaging Markers ◽  
And Diffusion ◽  
Joint Assessment ◽  
Diffusion Tensor Imaging Dti

Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4 Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD.

scholarly journals Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort

NeuroImage ◽  
2019 ◽  
Vol 188 ◽  
pp. 282-290 ◽  
Author(s):  
Claire Cury ◽  
Stanley Durrleman ◽  
David M. Cash ◽  
Marco Lorenzi ◽  
Jennifer M. Nicholas ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Spatiotemporal Analysis ◽  
Initial Application ◽  
Shape Changes

scholarly journals Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative clues for subtyping schizophrenia patients

2018 ◽  
Vol 11 (8) ◽  
pp. 678-687
Author(s):  
Liang Ma ◽  
Edmund T Rolls ◽  
Xiuqin Liu ◽  
Yuting Liu ◽  
Zeyu Jiao ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Brain Structures ◽  
Brain Regions ◽  
First Episode ◽  
Grey Matter Volume ◽  
Scale Analysis ◽  
Risk Genes ◽  
Multi Scale ◽  
Scale Scores ◽  
Multi Scale Analysis

AbstractAnalysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal regions. The patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for schizophrenia. Our results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease phenotypes. The method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.

scholarly journals Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD) and Alzheimer's disease (AD)

2013 ◽  
Vol 7 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Dong Seok Yi ◽  
Maxime Bertoux ◽  
Eneida Mioshi ◽  
John R. Hodges ◽  
Michael Hornberger
Keyword(s):  
Frontotemporal Dementia ◽  
Rating Scale ◽  
Brain Regions ◽  
Abnormal Behaviour ◽  
Behavioural Symptoms ◽  
Visual Rating ◽  
Prefrontal Cortical ◽  
Mri Scans ◽  
Visual Rating Scale ◽  
Cortical Regions

ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD) are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls) were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R) and Frontal System Behaviour Scale (FrSBe). Atrophy in prefrontal (VMPFC, DLPFC) and striatal (caudate, putamen) regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

scholarly journals Severe emphysematous cystitis complicated with perforation, bilateral renal cortical atrophy and sepsis: a case report

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093792
Author(s):  
Wen-Jun Zhang ◽  
Zheng-Ming Zhu ◽  
Hong-Liang Luo
Keyword(s):  
Case Report ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Cortical Atrophy ◽  
Test Results ◽  
Lower Abdomen ◽  
Current Case ◽  
Emphysematous Cystitis ◽  
Frequent Micturition ◽  
Timely Treatment

Emphysematous cystitis (EC) is a rare bladder infection characterized by the presence of gas in the wall or cavity of the bladder. Most patients with EC will present with the typical symptoms of cystitis (e.g. frequent micturition, urgent micturition and dysuria), but other signs include distension and pain in the lower abdomen, drum sounds on percussion and a large amount of gas in the bladder. There can also be other complications such as sepsis. However, it is usually characterized by the typical symptoms of infection combined with pneumatinuria, the passage of gas mixed with urine. The early stage of EC is mostly limited to the submucosa and the symptoms of infection can be mild. Some patients may have no obvious clinical symptoms. If the infection becomes severe, it may result in difficulty urinating and kidney dysfunction. Therefore, timely treatment of these rare bladder infections is essential. This current case report describes an 80-year-old female patient with severe EC complicated by significant bilateral ureteral dilatation, bilateral renal cortical atrophy and sepsis. The patient was successfully treated with antibiotics and surgery. This report provides clinical data, test results and treatment experience that might be useful for clinicians that are involved in the treatment of EC.

scholarly journals Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis

Neurology ◽  
2020 ◽  
Vol 94 (15) ◽  
pp. e1580-e1591 ◽  
Author(s):  
James D. Doecke ◽  
Virginia Pérez-Grijalba ◽  
Noelia Fandos ◽  
Christopher Fowler ◽  
Victor L. Villemagne ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Standardized Uptake Value ◽  
Imaging Biomarkers ◽  
Control Group ◽  
Amyloid Pet ◽  
Time Points ◽  
Healthy Control ◽  
Ε4 Allele ◽  
Amyloid Aβ ◽  
Rate Of Failure

ObjectiveTo explore whether the plasma total β-amyloid (Aβ) Aβ42/Aβ40 ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort.MethodsTaking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total Aβ42/Aβ40 ratio in plasma (TP42/40) with regard to neocortical Aβ burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aβ-PET status and correlation (and agreement) with SUVR.ResultsThe TP42/40 plasma ratio was significantly reduced in amyloid-PET–positive participants at all time points (p < 0.0001). Adjusting for covariates age, gender, APOE ε4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance (p = 0.006). Correlations with SUVR were similar across each time point, with Spearman ρ reaching −0.64 (p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found.ConclusionsThe current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease.Classification of evidenceThis study provides Class II evidence that plasma total Aβ42/Aβ40 ratio is associated with neocortical amyloid burden as measured by PET SUVR.

scholarly journals Local angiotensin-(1–7) administration improves microvascular endothelial function in women who have had preeclampsia

2020 ◽  
Vol 318 (1) ◽  
pp. R148-R155 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Lacy M. Alexander
Keyword(s):  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
No Synthase ◽  
Ang Ii ◽  
Healthy Control ◽  
History Of ◽  
Increased Sensitivity ◽  
Microvascular Endothelial ◽  
Synthase Inhibitor ◽  
Microvascular Endothelial Function

Despite remission of clinical symptoms postpartum, women who have had preeclampsia demonstrate microvascular endothelial dysfunction, mediated in part by increased sensitivity to angiotensin II (ANG II). Angiotensin-(1–7) [Ang-(1–7)] is an endogenous inhibitor of the actions of ANG II and plausible druggable target in women who had preeclampsia. We therefore examined the therapeutic potential of Ang-(1–7) in the microvasculature of women with a history of preeclampsia (PrEC; n = 13) and parity-matched healthy control women (HC; n = 13) hypothesizing that administration of Ang-(1–7) would increase endothelium-dependent dilation and nitric oxide (NO)-dependent dilation and decrease ANG II-mediated constriction in PrEC. Using the cutaneous microcirculation, we assessed endothelium-dependent vasodilator function in response to graded infusion of acetylcholine (ACh; 10−7 to 102 mmol/L) in control sites and sites treated with 15 mmol/L NG-nitro-l-arginine methyl ester (l-NAME; NO-synthase inhibitor), 100 µmol/L Ang-(1–7), or 15 mmol/L l-NAME + 100 µmol/L Ang-(1–7). Vasoconstrictor function was measured in response to ANG II (10−20-10−4 mol/L) in control sites and sites treated with 100 µmol/L Ang-(1–7). PrEC had reduced endothelium-dependent dilation ( P < 0.001) and NO-dependent dilation ( P = 0.04 vs. HC). Ang-(1–7) coinfusion augmented endothelium-dependent dilation ( P < 0.01) and NO-dependent dilation ( P = 0.03) in PrEC but had no effect in HC. PrEC demonstrated augmented vasoconstrictor responses to ANG II ( P < 0.01 vs. HC), which was attenuated by coinfusion of Ang-(1–7) ( P < 0.001). Ang-(1–7) increased endothelium-dependent vasodilation via NO synthase-mediated pathways and attenuated ANG II-mediated constriction in women who have had preeclampsia, suggesting that Ang-(1–7) may be a viable therapeutic target for improved microvascular function in women who have had a preeclamptic pregnancy.

An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium

2019 ◽  
Vol 50 (12) ◽  
pp. 2034-2045 ◽  
Author(s):  
Ting Yat Wong ◽  
Joaquim Radua ◽  
Edith Pomarol-Clotet ◽  
Raymond Salvador ◽  
Anton Albajes-Eizagirre ◽  
...  
Keyword(s):  
Brain Mri ◽  
Brain Structures ◽  
Primary Diagnosis ◽  
Positive Symptoms ◽  
Formal Thought Disorder ◽  
Midcingulate Cortex ◽  
Neuroimaging Data ◽  
Mri Scans ◽  
Cortical Gray Matter ◽  
Abnormal Brain

AbstractBackgroundPositive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

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