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Abstract Background Sirtuin 1 (Sirt1) is a recognized longevity gene and has been shown to be associated with aging and its related diseases. Hippocampal volume is considered to be the most sensitive brain imaging phenotype for cognition, but the effect of Sirt1 on hippocampal morphology during aging has not been reported. Results Herein, we investigated the effect of conditional Sirt1 knockdown on hippocampal volume in middle-aged mice, as well as its cognitive function and the underlying molecular mechanisms. Brain structural magnetic resonance imaging (MRI) showed that adeno-associated virus (AAV) mediated hippocampal Sirt1 knockdown caused hippocampal atrophy in 8-month-old mice. Open field test (OFT) and Morris Water Maze (MWM) test revealed that hippocampal Sirt1 knockdown significantly weakened spatial learning and memory of mice without effect on anxiety and exploratory behavior. Western blotting analysis showed that P-tau levels at serine 396 epitope were significantly increased with slightly decreased T-tau levels, while PSD95 and NMDAR2B levels were obviously reduced, indicating that hippocampal Sirt1 knockdown could activate tau hyperphosphorylation and synaptic damage. Conclusions This work revealed that Sirt1 is an important protective gene against hippocampal atrophy and its induced cognitive impairment during aging, providing potential therapeutic targets for the prevention and intervention of aging-related neuropsychic diseases.

Background: Sirtuin 1 (Sirt1) is a recognized longevity gene and has been shown to be associated with aging and its related diseases. Hippocampal volume is considered to be the most sensitive brain imaging phenotype for cognition, but the effect of Sirt1 on hippocampal morphology during aging has not been reported.Results: Herein, we investigated the effect of conditional Sirt1 knockdown on hippocampal volume in middle-aged mice, as well as its cognitive function and the underlying molecular mechanisms. Brain structural magnetic resonance imaging (MRI) showed that adeno-associated virus (AAV) mediated hippocampal Sirt1 knockdown caused hippocampal atrophy in 8-month-old mice. Open field test (OFT) and Morris Water Maze (MWM) test revealed that hippocampal Sirt1 knockdown significantly weakened spatial learning and memory of mice without effect on anxiety and exploratory behavior. Western blotting analysis showed that P-tau levels at serine 396 epitope were significantly increased with slightly decreased T-tau levels, while PSD95 and NMDAR2B levels were obviously reduced, indicating that hippocampal Sirt1 knockdown could activate tau hyperphosphorylation and synaptic damage.Conclusions: This work revealed that Sirt1 is an important protective gene against hippocampal atrophy and its induced cognitive impairment during aging, providing potential therapeutic targets for the prevention and intervention of aging-related neuropsychic diseases. [ABSTRACT FROM AUTHOR]

Background Anticholinergic drugs block muscarinic receptors in the body. They are commonly prescribed for a variety of indications and their use has previously been associated with dementia and cognitive decline. Methods In UK Biobank participants with linked health-care records (n=171,266, aged 40-71 at baseline), we calculated total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general intelligence, 9 separate cognitive domains, total brain volume, volumes of 68 cortical and 16 subcortical areas, and fractional anisotropy and median diffusivity of 25 white-matter tracts. Results Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (6/9 FDR-adjusted significant associations, std. betas range: -0.033, -0.006). The association was mostly driven by antibiotics (std. beta=-0.029, 95% p0.07). Discussion Anticholinergic burden is mildly associated with poorer cognition, but there is little evidence for an effect for measures of brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability.

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

Label fusion is one of the key steps in multi-atlas based segmentation of structural magnetic resonance (MR) images. Although a number of label fusion methods have been developed in literature, most of those existing methods fail to address two important problems, i.e., (1) compared with boundary voxels, inner voxels usually have higher probability (or reliability) to be correctly segmented, and (2) voxels with high segmentation reliability (after initial segmentation) can help refine the segmentation of voxels with low segmentation reliability in the target image. To this end, we propose a general reliability-based robust label fusion framework for multi-atlas based MR image segmentation. Specifically, in the first step, we perform initial segmentation for MR images using a conventional multi-atlas label fusion method. In the second step, for each voxel in the target image, we define two kinds of reliability, including the label reliability and spatial reliability that are estimated based on the soft label and spatial information from the initial segmentation, respectively. Finally, we employ voxels with high label-spatial reliability to help refine the label fusion process of those with low reliability in the target image. We incorporate our proposed framework into four well-known label fusion methods, including locally-weighted voting (LWV), non-local mean patch-based method (PBM), joint label fusion (JLF) and sparse patch-based method (SPBM), and obtain four novel label-spatial reliability-based label fusion approaches (called ls-LWV, ls-PBM, ls-JLF, and ls-SPBM). We validate the proposed methods in segmenting ROIs of brain MR images from the NIREP, LONI-LPBA40 and ADNI datasets. The experimental results demonstrate that our label-spatial reliability-based label fusion methods outperform the state-of-the-art methods in multi-atlas image segmentation. [ABSTRACT FROM AUTHOR]

Background: Head motion during brain structural MRI scans biases brain morphometry measurements but quantitative retrospective methods estimating head motion from structural MRI have not been evaluated.Purpose: To verify the hypothesis that two metrics retrospectively computed from MR images: 1) average edge strength (AES, reduced with image blurring) and 2) entropy (ENT, increased with blurring and ringing artifacts) could be sensitive to in-scanner head motion during acquisition of T1 -weighted MR images.Study Type: Retrospective.Population/subjects/phantom/specimen/animal Model: In all, 83 healthy control (HC) and 120 Parkinson's disease (PD) patients.Field Strength/sequence: 3D magnetization-prepared rapid gradient-echo (MPRAGE) images at 3T.Assessment: We 1) compared AES and ENT distribution between HC and PD; 2) evaluated the correlation between tremor score (TS) and AES (or ENT) in PD; and 3) investigated cortical regions showing an association between AES (or ENT) and local and network-level covariance measures of cortical thickness (CT), gray to white matter contrast (GWC) and gray matter density maps (GMx).Statistical Tests: 1) Student's t-test. 2) Spearman's rank correlation. 3) General linear model and partial least square analysis.Results: AES, but not ENT, differentiated HC and PD (P = 0.02, HC median AES = 39.8, interquartile range = 9.8, PD median AES = 37.6, interquartile range = 8.1). In PD, AES correlated negatively with TS (ρ = -0.21, P = 0.02) and showed a significant relationship (|Z| >3, P < 0.001) with structural covariance of CT and GWC in 54 out of 68 cortical regions.Data Conclusion: In clinical populations prone to head motion, AES can provide a reliable retrospective index of motion during structural scans, identifying brain areas whose morphometric measures covary with motion.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:927-937. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample., Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures., Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3-3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4-4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2-3.2), cranial deformities (OR 2.4, 95 % CI: 1.0-5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0-2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3-9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1-6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis., Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)