Search

Objective: This study mapped the topological configuration of the default mode network (DMN) in patients with depressive symptoms after acute ischemic stroke., Methods: The study sample comprised 63 patients: 36 with poststroke depressive symptoms (PSD) and 37 without PSD matched according to age, gender and the severity of stroke. PSD was defined by a cutoff of ≥ 7 on the 15-item Geriatric Depression Scale (GDS). Resting-state functional magnetic resonance imaging (fMRI) was used to examine functional connectivity (FC) to reconstruct the DMN. Network based statistics estimated the FC differences of the DMN between the PSD and non-PSD groups. Graph theoretical approaches were used to characterize the topological properties of this network., Results: The study sample mainly comprised patients with mild to moderate stroke. A widespread hyper-connected configuration of the functional DMN was characterized in PSD group. The orbital frontal, dorsolateral prefrontal, dorsal medial prefrontal and, ventromedial prefrontal corticis, the middle temporal gyrus and the inferior parietal lobule were the functional hubs related to PSD. The nodal topology in inferior parietal lobule and superior frontal gyrus, overlapping with dorsal medial prefrontal and, ventromedial prefrontal cortices, tended to be functionally integrated in patients with PSD. After False Discovery Rate correction, no significant difference between the PSD and non-PSD groups was found with respect to the global and nodal metrics of the DMN. However, the correlations between these altered network metrics and severity of PSD were lacking., Limitations: The diagnosis of PSD was based on the GDS score rather than established with a structured clinical interview., Conclusions: The DMN in PSD was functionally integrated and more specialized in some core hubs such as the inferior parietal lobule and dorsal prefrontal cortex. The configuration of the subnetwork like DMN may be more essential in the pathogenesis of PSD than single stroke lesions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

BackgroundThe differential diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD.MethodsIn this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in "FTD dominant" structures over that obtained from "AD dominant" structures. The weights and the identification of "FTD/AD dominant" structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases.ResultsAD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p

Alzheimer's disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.