14 research outputs found
brainlife.io: a decentralized and open-source cloud platform to support neuroscience research
Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants
The Chinese Verbal Learning Test Specifically Assesses Hippocampal State
BackgroundRecently, the Chinese Verbal Learning Test (ChVLT) was developed to assess episodic memory in Chinese speakers. The goal of this analysis was to determine whether memory consolidation as measured by the ChVLT was specifically associated with hippocampal volume in patients with cognitive impairment.MethodsWe administered the ChVLT to 22 Chinese-speaking patients with mild cognitive impairment and 9 patients with dementia and obtained hippocampal and cortical volumes from T1-weighted magnetic resonance imaging.ResultsLinear regression revealed that hippocampal volume explained 9.9% of the variance in delayed memory (P = .018) after controlling for the effects of age, education, immediate recall after the last learning trial, overall level of cognitive impairment, and volumes of other cortical regions.ConclusionThese results indicate that the ChVLT is specifically correlated with hippocampal volume, supporting its utility for detecting hippocampal disease and monitoring hippocampal state over time
The Chinese Verbal Learning Test Specifically Assesses Hippocampal State
BACKGROUND: Recently, the Chinese Verbal Learning Test (ChVLT) was developed to assess episodic memory in Chinese speakers. The goal of this analysis was to determine whether memory consolidation as measured by the ChVLT was specifically associated with hippocampal volume in patients with cognitive impairment. METHODS: We administered the ChVLT to 22 Chinese-speaking patients with mild cognitive impairment and 9 patients with dementia and obtained hippocampal and cortical volumes from T1-weighted magnetic resonance imaging. RESULTS: Linear regression revealed that hippocampal volume explained 9.9% of the variance in delayed memory (P = .018) after controlling for the effects of age, education, immediate recall after the last learning trial, overall level of cognitive impairment, and volumes of other cortical regions. CONCLUSION: These results indicate that the ChVLT is specifically correlated with hippocampal volume, supporting its utility for detecting hippocampal disease and monitoring hippocampal state over time
Age-dependent effects of APOE ε4 in preclinical Alzheimer's disease.
The ε4 allele of apolipoprotein E (APOE) is the strongest known common genetic risk factor for Alzheimer's disease (AD) and alters age of onset in retrospective studies. Here, we longitudinally test the effects of APOE ε4 genotype and age during progression from normal cognition to AD.Using data from 5381 cognitively normal older individuals and Cox proportional hazards models, we longitudinally tested the effects of APOE genotype on progression from normal cognition to mild cognitive impairment (MCI) or AD in four age strata (<60, 60-70, 70-80, 80 + ) and with a sliding window approach between ages 60 and 85.We found that APOE ε4 carrier status and dosage significantly influenced progression to MCI or AD in all four age groups and that APOE ε4-associated progression risk peaked between ages 70 and 75. We confirmed APOE ε4-associated progression risk in a subset of the cohort with pathologically proven diagnoses.Our findings indicate that in clinically normal individuals, APOE ε4 status significantly predicts progression to MCI or AD across older adulthood and that this risk varies with age. This information will be useful as therapeutic interventions become available and clinical decisions can be individually tailored based on age and genetic data
Thigh-length compression stockings and DVT after stroke
Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease
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Radiogenomics of C9orf72 Expansion Carriers Reveals Global Transposable Element Derepression and Enables Prediction of Thalamic Atrophy and Clinical Impairment.
Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used FreeSurfer software to assess the effects of C9orf72 HRE and clinical diagnosis (n = 78 individuals, male and female) on atrophy of thalamic nuclei. We also generated a novel, human, whole-blood RNA-sequencing dataset to determine the relationships among peripheral C9orf72 expression, TE activation, thalamic atrophy, and clinical severity (n = 114 individuals, male and female). We confirmed global thalamic atrophy and reduced C9orf72 expression in HRE carriers. Moreover, we identified disproportionate atrophy of the right mediodorsal lateral nucleus in HRE carriers and showed that C9orf72 expression associated with clinical severity, independent of thalamic atrophy. Strikingly, we found global peripheral activation of TEs, including the human endogenous LINE-1 element L1HS L1HS levels were associated with atrophy of multiple pulvinar nuclei, a thalamic region implicated in C9-FTD. Integration of peripheral transcriptomic and neuroimaging data from human HRE carriers revealed atrophy of specific thalamic nuclei, demonstrated that C9orf72 levels relate to clinical severity, and identified marked derepression of TEs, including L1HS, which predicted atrophy of FTD-relevant thalamic nuclei.SIGNIFICANCE STATEMENT Pathogenic repeat expansion in C9orf72 is the most frequent genetic cause of FTD and amyotrophic lateral sclerosis (ALS; C9-FTD/ALS). The clinical, neuroimaging, and pathologic features of C9-FTD/ALS are well characterized, whereas the intersections of transcriptomic dysregulation and brain structure remain largely unexplored. Herein, we used a novel radiogenomic approach to examine the relationship between peripheral blood transcriptomics and thalamic atrophy, a neuroimaging feature disproportionately impacted in C9-FTD/ALS. We confirmed reduction of C9orf72 in blood and found broad dysregulation of transposable elements-genetic elements typically repressed in the human genome-in symptomatic C9orf72 expansion carriers, which associated with atrophy of thalamic nuclei relevant to FTD. C9orf72 expression was also associated with clinical severity, suggesting that peripheral C9orf72 levels capture disease-relevant information