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Human Brain Antioxidants During Oxidative Stress

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01713816
Recruitment Status : Completed
First Posted : October 25, 2012
Last Update Posted : May 3, 2019
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Minnesota

Brief 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.

Condition or disease
Oxidative Stress Alzheimer's Disease Aging

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.

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Study Type : Observational
Actual Enrollment : 52 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Noninvasive Antioxidant Quantification in the Human Brain Under Oxidative Stress
Study Start Date : June 2013
Actual Primary Completion Date : June 1, 2017
Actual Study Completion Date : July 24, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antioxidants

Elderly control
Healthy elderly subjects age and gender matched to the AD cohort, predominantly male

Primary Outcome Measures :
  1. Antioxidant in Alzheimers [ Time Frame: 1 year ]
    Occipital cortex and posterior cingulate ascorbate and glutathione concentration in young and elder patients as well as in patients with AD

Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 89 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Inclusion Criteria:

Age and gender match to AD patients: age range 65-89:

note that we anticipate that our patients will be predominantly male, so we are NOT likely to enroll females for this portion of the study

Exclusion Criteria::

Claustrophobia Implanted metal devices Pregnancy > RDA dietary supplements

≥ 5 F+V per day Smoking Depression Poor health or systemic illness Medial history of or evidence for cognitive problems Unstable medication usage Neurological problems Psychiatric disorder Substance abuse Usage of investigational drugs Inability to complete cognitive tests written in and calibrated for English speakers Inadequate vision or hearing to accommodate participation MMSE (dementia) score ≤ 26

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01713816

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United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
National Institute on Aging (NIA)
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Principal Investigator: Melissa Terpstra, PhD University of Minnesota
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Responsible Party: University of Minnesota Identifier: NCT01713816    
Other Study ID Numbers: 1208M18321
R01AG039396 ( U.S. NIH Grant/Contract )
First Posted: October 25, 2012    Key Record Dates
Last Update Posted: May 3, 2019
Last Verified: May 2019
Keywords provided by University of Minnesota:
Alzheimer's disease
Magnetic Resonance Spectroscopy
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders