title: Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults.
abstract: BACKGROUND
  Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age.
  
  
  METHODS
  We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS)1H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning.
  
  
  RESULTS
  Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age.
  
  
  CONCLUSIONS
  These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors.
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Porges
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Woods
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Nicolaas A J
authors.initials: NA
authors.lastname: Puts
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Huaihou
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Garcia
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Talia R
authors.initials: TR
authors.lastname: Seider
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Damon G
authors.initials: DG
authors.lastname: Lamb
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: John B
authors.initials: JB
authors.lastname: Williamson
authors.affiliation: Center for Cognitive Aging and Memory (ECP, AJW, HC, AMG, TRS, DGL, JBW, RAC), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric Research; Department of Neuroscience (AJW), University of Florida, Gainesville, Florida; FM Kirby Center for Functional Brain Imaging (RAEE, NAJP, ADH), Kennedy Krieger Institute; Russell H. Morgan Department of Radiology and Radiological Science (RAEE, NAJP, ADH), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology (ADH), CAIR Program (ADH), Alberta Children's Hospital Research Institute, University of Calgary; Hotchkiss Brain Institute (ADH), University of Calgary, Calgary, Alberta, Canada; Department of Biostatistics (HC); Department of Clinical and Health Psychology (AMG, TRS), University of Florida; Brain Rehabilitation and Research Center (DGL, JBW), Malcom Randall Veterans Affairs Medical Center; and Center for Neuropsychological Studies (JBW), Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cohen
keywords: Aging; Cognition; GABA; MEGA-PRESS; MRS; γ-Aminobutyric