@article{ecc9b8b267a54b64ad260092b79e5b17,
title = "Ventricular and periventricular anomalies in the aging and cognitively impaired brain",
abstract = "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.",
keywords = "Aging, Cognitive impairment, Ependymal cells, Gliosis, Periventricular edema, Ventriculomegaly",
author = "{For the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative} and Todd, {Krysti L.} and Tessa Brighton and Norton, {Emily S.} and Samuel Schick and Wendy Elkins and Olga Pletnikova and Fortinsky, {Richard H.} and Troncoso, {Juan C.} and Molfese, {Peter J.} and Resnick, {Susan M.} and Conover, {Joanne C.}",
note = "Funding Information: We would like to thank the ADNI and Baltimore Longitudinal Study of Aging (BLSA) volunteers for their support and participation. Data collection and sharing for this project was funded in part by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research and Development, LLC.; Johnson and Johnson Pharmaceutical Research and Development LLC.; Lumosity; Lundbeck; Merck and Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The BLSA is supported by the Intramural Research Program, NIA, NIH. We also acknowledge support from the NIH/NINDS (R01NS50338 to JCC). The Connecticut Institute for Clinical and Translational Science provided support to the UConn Center on Aging to facilitate data analysis and presentation guidance. Publisher Copyright: {\textcopyright} 2018 Todd, Brighton, Norton, Schick, Elkins, Pletnikova, Fortinsky, Troncoso, Molfese, Resnick and Conover for the Alzheimer's Disease Neuroimaging Initiative.",
year = "2018",
month = jan,
day = "12",
doi = "10.3389/fnagi.2017.00445",
language = "English (US)",
volume = "9",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Research Foundation",
number = "JAN",
}