Maintaining cognitive vitality with aging and reducing the risks for Alzheimer's disease (AD) are urgent national health priorities. The goal of this revision is to strengthen the currently funded grant """"""""Mild cognitive impairment: cerebrovascular dysfunction and exercise training"""""""" (R01 AG033106) to determine whether aerobic exercise training reduces brain amyloid burden and ameliorates chronic brain inflammation in patients with mild cognitive impairment (MCI) - a transitional stage between normal aging and AD. We will accomplish the following specific aims.
Aim 1 : To determine whether exercise training reduces brain amyloid burden in patients with MCI. Brain amyloid burden in patients with MCI before and after one year of aerobic exercise training will be measured with positron emission tomography (PET) amyloid imaging using 18F-AV-45 and immunoassay (ELISA) of cerebral spinal fluid (CSF) levels of A2, tau and phosphorylated tau.
Aim 2 : To determine whether exercise training ameliorates chronic brain inflammation in patients with MCI. Chronic brain inflammation in patients with MCI will be assessed using quantitative multiplex immunoassay methods to measure plasma and CSF levels of inflammatory biomarkers such as TNF-1, IL-12, and IL-6.
Aim 3 : To determine whether reductions in brain amyloid burden and/or inflammation are correlated with improvement in brain perfusion. Brain perfusion will be measured using non-invasive transcranial Doppler and perfusion MRI (via arterial spin labeling techniques). Together with the parent grant, we also will determine whether these changes in neuroimaging and inflammatory biomarkers are correlated with changes in cognitive function. Understanding the underlying mechanisms by which exercise improves brain health is essential for developing effective interventions to maintain cognitive vitality with aging and to prevent or slow Alzheimer's disease.

Public Health Relevance

Maintaining cognitive vitality with aging and reducing the risks for Alzheimer's disease (AD) are urgent national health priorities. The goal of this study is to understand the underlying mechanisms by which exercise preserves or improves cognitive function in patients with mild cognitive impairment (MCI) - a transitional stage between normal aging and AD. The outcome of this study is potentially important for developing effective interventions to prevent or slow Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG033106-02S1
Application #
8108170
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Ryan, Laurie M
Project Start
2009-09-15
Project End
2013-08-31
Budget Start
2011-04-01
Budget End
2011-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$423,879
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S et al. (2015) Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex 25:396-405
Tarumi, Takashi; Harris, Thomas S; Hill, Candace et al. (2015) Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment. Neurology 85:1922-9

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