Human Brain Antioxidants During Oxidative Stress
Condition: Oxidative Stress; Alzheimer's Disease; Aging
MeSH terms: Alzheimer Disease
Study type: Observational

Summary: 
      Antioxidants are important for having a good memory and for smart thinking when people get
      old, and that is important for everyone's quality of life. This research will find out if
      normal aging and Alzheimer's disease use up brain antioxidants. It will develop a new imaging
      tool that can help doctors to stop cognitive decline.
    

Detailed description: 
      The objective of this proposal is to advance the mission of improving the health and
      well-being of older Americans by augmenting ongoing dementia prevention and treatment
      initiatives. It undertakes research on dementia associated with both normal aging and AD. A
      new scientist will develop a novel and powerful human brain antioxidant assay using
      state-of-the art instrumentation. The approach will be translated to the clinical environment
      so that it can be disseminated for use with new research. Specifically, the concentrations of
      two important antioxidants, ascorbate (Asc) and glutathione (GSH) will be measured
      noninvasively in the human brain. One aim is to measure whether a recent finding of lower
      brain GSH concentration in the occipital cortex of cognitively normal elder subjects is also
      found in the posterior cingulate cortex, and whether human brain Asc homeostasis persists in
      both brain regions. A complementary specific aim is to determine whether lower brain GSH
      concentration also occurs under the oxidative stress associated with Alzheimer's disease
      (AD). At the same time, data measured in subjects with AD have potential to advance this
      powerful new technology toward discovering an early stage biomarker. A sub aim is to make
      this technology available to a wide range of physicians and investigators. As such, data
      processing will be fully automated using commercially available software. This novel
      noninvasive technology facilitates a paradigm shift from systemic assays to quantifying
      antioxidants directly in the affected brain region. The approach will take advantage of state
      of the art 7 T instrumentation while developing analogous methods on a clinical 3 T scanner.
      The process of optimizing magnetic resonance spectroscopy (MRS) for quantification of brain
      Asc and GSH concentrations necessitated reliable quantification of an extensive neurochemical
      profile (i.e. 19 brain metabolites), which includes the four compounds that are typically
      observed. Spectra acquired in stimulated echo acquisition mode (STEAM) will be de-convolved
      quantitatively into contributions from the metabolites that contribute discernable resonances
      using a linear combination model approach (LCModel). Reliable quantification of brain GSH and
      Asc concentrations will first be achieved using ultra high field MRS with multiple transmit
      coil technology and accompanying radiofrequency (B1) shimming, then translated to a lower
      field clinical platform. Successful completion will determine whether low brain glutathione
      concentration is widespread in the elder human brain and whether this difference is
      exacerbated by AD.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        All data have been accrued for the healthy aging aim, which included healthy people age
        18-22 and age 70-89. To study the second aim, 23 patients with AD will be recruited from
        the Minneapolis, MN VA medical center. 23 age - and gender- matched controls will be
        recruited to study neurodegenerative disease associated demand on the antioxidant system.
        We do NOT currently have the resources to screen candidates with AD who are not current
        patients at the VA medical center in Minneapolis.
      
Keywords: Glutathione; Ascorbate; Alzheimer's disease; Aging; Magnetic Resonance Spectroscopy