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Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain.

Frontiers in aging neuroscience | 2017

Ventriculomegaly (expansion of the brain's fluid-filled ventricles), a condition commonly found in the aging brain, results in areas of gliosis where the ependymal cells are replaced with dense astrocytic patches. Loss of ependymal cells would compromise trans-ependymal bulk flow mechanisms required for clearance of proteins and metabolites from the brain parenchyma. However, little is known about the interplay between age-related ventricle expansion, the decline in ependymal integrity, altered periventricular fluid homeostasis, abnormal protein accumulation and cognitive impairment. In collaboration with the Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer's Disease Neuroimaging Initiative (ADNI), we analyzed longitudinal structural magnetic resonance imaging (MRI) and subject-matched fluid-attenuated inversion recovery (FLAIR) MRI and periventricular biospecimens to map spatiotemporally the progression of ventricle expansion and associated periventricular edema and loss of transependymal exchange functions in healthy aging individuals and those with varying degrees of cognitive impairment. We found that the trajectory of ventricle expansion and periventricular edema progression correlated with degree of cognitive impairment in both speed and severity, and confirmed that areas of expansion showed ventricle surface gliosis accompanied by edema and periventricular accumulation of protein aggregates, suggesting impaired clearance mechanisms in these regions. These findings reveal pathophysiological outcomes associated with normal brain aging and cognitive impairment, and indicate that a multifactorial analysis is best suited to predict and monitor cognitive decline.

Pubmed ID: 29379433 RIS Download

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: P50 AG005146
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS050338
  • Agency: NINDS NIH HHS, United States
    Id: R21 NS098091
  • Agency: NIA NIH HHS, United States
    Id: U01 AG024904

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FreeSurfer (tool)

RRID:SCR_001847

Open source software suite for processing and analyzing human brain MRI images. Used for reconstruction of brain cortical surface from structural MRI data, and overlay of functional MRI data onto reconstructed surface. Contains automatic structural imaging stream for processing cross sectional and longitudinal data. Provides anatomical analysis tools, including: representation of cortical surface between white and gray matter, representation of the pial surface, segmentation of white matter from rest of brain, skull stripping, B1 bias field correction, nonlinear registration of cortical surface of individual with stereotaxic atlas, labeling of regions of cortical surface, statistical analysis of group morphometry differences, and labeling of subcortical brain structures.Operating System: Linux, macOS.

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ADNI - Alzheimer's Disease Neuroimaging Initiative (tool)

RRID:SCR_003007

Database of the results of the ADNI study. ADNI is an initiative to develop biomarker-based methods to detect and track the progression of Alzheimer's disease (AD) that provides access to qualified scientists to their database of imaging, clinical, genomic, and biomarker data.

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Intramural Research Program (tool)

RRID:SCR_012734

A research program of the NIA which focuses on neuroscience, aging biology, and translational gerontology. The central focus of the program's research is understanding age-related changes in physiology and the ability to adapt to environmental stress, and using that understanding to develop insight about the pathophysiology of age-related diseases. The IRP webpage provides access to other NIH resources such as the Biological Biochemical Image Database, the Bioinformatics Portal, and the Baltimore Longitudinal Study of Aging.

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Foundation for the National Institutes of Health (tool)

RRID:SCR_004493

A public charity whose mission is to support the NIH in its mission to improve health, by forming and facilitating public-private partnerships for biomedical research and training. Its vision is Building Partnerships for Discovery and Innovation to Improve Health. The FNIH draws together the world''s foremost researchers and resources, pressing the frontier to advance critical discoveries. They are recognized as the number-one medical research charity in the countryleveraging support, and convening high level partnerships, for the greatest impact on the most urgent medical challenges we face today. Grants are awarded as part of a public-private partnership with the National Heart, Lung, and Blood Institute (NHLBI) on behalf of The Heart Truth in support of women''s heart health education and research. Funding for the Community Action Program is provided by the FNIH through donations from individuals and corporations including The Heart Truth partners Belk Department Stores, Diet Coke, and Swarovski. Successful biomedical research relies upon the knowledge, training and dedication of those who conduct it. Bringing multiple disciplines to bear on health challenges requires innovation and collaboration on the part of scientists. Foundation for NIH partnerships operate in a variety of ways and formats to recruit, train, empower and retain their next generation of researchers. From lectures and multi-week courses, to scholarships and awards through fellowships and residential training programs, their programs respond to the needs of scientists at every level and stage in their careers.

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3D Slicer (tool)

RRID:SCR_005619

A free, open source software package for visualization and image analysis including registration, segmentation, and quantification of medical image data. Slicer provides a graphical user interface to a powerful set of tools so they can be used by end-user clinicians and researchers alike. 3D Slicer is natively designed to be available on multiple platforms, including Windows, Linux and Mac Os X. Slicer is based on VTK (http://public.kitware.com/vtk) and has a modular architecture for easy addition of new functionality. It uses an XML-based file format called MRML - Medical Reality Markup Language which can be used as an interchange format among medical imaging applications. Slicer is primarily written in C++ and Tcl.

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Clinical Dementia Rating (tool)

RRID:SCR_003678

A numeric scale used to quantify the severity of symptoms of dementia (i.e. its stage). Using a structured-interview protocol, a qualified health professional assesses a patient's cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores in each of these are combined to obtain a composite score ranging from 0 through 3. (Adapted from Wikipedia)

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Mango (tool)

RRID:SCR_009603

A viewer for medical research images that provides analysis tools and a user interface to navigate image volumes. There are three versions of Mango, each geared for a different platform: * Mango ? Desktop ? Mac OS X, Windows, and Linux * webMango ? Browser ? Safari, Firefox, Chrome, and Internet Explorer * iMango ? Mobile ? Apple iPad Key Features: * Built-in support for DICOM, NIFTI, Analyze, and NEMA-DES formats * Customizable: Create plugins, custom filters, color tables, file formats, and atlases * ROI Editing: Threshold and component-based tools for painting and tracing ROIs * Surface Rendering: Interactive surface models supporting cut planes and overlays * Image Registration: Semi-automatic image coregistration and manual transform editing * Image Stacking: Threshold and transparency-based image overlay stacking * Analysis: Histogram, cross-section, time-series analysis, image and ROI statistics * Processing: Kernel and rank filtering, arithmetic/logic image and ROI calculators

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