Dorsolateral prefrontal cortex GABA deficit in older adults with sleep-disordered breathing.

TitleDorsolateral prefrontal cortex GABA deficit in older adults with sleep-disordered breathing.
Publication TypeJournal Article
Year of Publication2017
AuthorsPereira AC, Mao X, Jiang CS, Kang G, Milrad S, McEwen BS, Krieger AC, Shungu DC
JournalProc Natl Acad Sci U S A
Volume114
Issue38
Pagination10250-10255
Date Published2017 09 19
ISSN1091-6490
KeywordsAged, Case-Control Studies, Female, gamma-Aminobutyric Acid, Glutamates, Glutamine, Hippocampus, Humans, Male, Middle Aged, Prefrontal Cortex, Sleep Apnea Syndromes
Abstract

Sleep-disordered breathing (SDB) is a common disorder in aging that is associated with cognitive decline, including significant executive dysfunction, for which the neurobiological underpinnings remain poorly understood. Using proton magnetic resonance spectroscopy (1H MRS), this study assessed whether dysregulation of the homeostatic balance of the major inhibitory and excitatory amino acid neurotransmitter systems of γ-aminobutyric acid (GABA) and glutamate, respectively, play a role in SDB. Levels of GABA and those of the combined resonances of glutamate and glutamine (Glx), were measured by 1H MRS in the left dorsolateral prefrontal cortex (l-DLPFC) and bilateral hippocampal regions of 19 older adults (age ± SD: 66.1 ± 1.9 years) with moderate to severe SDB, defined as having an Apnea-Hypopnea Index (AHI) greater than 15 as assessed by polysomnography, and in 14 older adults (age ± SD: 62.3 ± 1.3 years) without SDB (AHI < 5). In subjects with SDB, levels of l-DLPFC GABA, but not Glx, were significantly lower than in control subjects ( < 0.0002). Additionally, there was a negative correlation between l-DLPFC GABA levels, but not Glx, and SDB severity by AHI ( = -0.68, < 0.0001), and a positive correlation between l-DLPFC GABA levels, but not Glx, and minimal oxygen saturation during sleep ( = 0.62, = 0.0005). By contrast, no group differences or oxygenation associations were found for levels of GABA or Glx in right or left hippocampal region. These findings are interpreted in terms of a pathophysiological model of SDB in which hypoxia-mediated inhibitory neurotransmission deficit in DLPFC could lead to hyperexcitability and, potentially neuronal dysfunction and cognitive decline.

DOI10.1073/pnas.1700177114
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID28874569
PubMed Central IDPMC5617247
Grant ListK76 AG054772 / AG / NIA NIH HHS / United States
S10 OD021782 / OD / NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
R01 MH075895 / MH / NIMH NIH HHS / United States

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