Is fMRI confounded by age related changes to the cererbral vascular reserve?

Principal Investigator:
Paul J. Laurienti, M.D., Ph.D.

Investigators and Personnel:
Robert A. Kraft, Ph.D.

Vascular Reserve and Age Study

The question “What is successful aging?” is being popularized with the aging of the baby boomers. Neuroscientists are trying to answer this question using a variety of functional brain imaging techniques, including fMRI. fMRI does not directly measure brain activity but relies on local changes in cerebral blood flow (CBF) as a surrogate marker for brain activity. If a subject’s blood flow in response to an increase in brain activity is altered or disrupted for any reason such as age, drugs, or disease then a direct and meaningful interpretation of fMRI results is difficult. Currently, there are no studies demonstrating the degree to which age related changes to the cerebral vascular reserve (CVR) alter fMRI findings. Given that the CVR is known to change with age, this remains a critical knowledge gap in geriatric neuroscience. This proposal will fill this knowledge gap by evaluating the degree to which neurovascular changes confound fMRI studies in older adults and test a relatively simple method to account for these changes. Specific Aim 1 determines the extent to which age-related decreases in CVR account for reductions in the fMRI signal by incorporating CVR, as measured with perfusion MRI, directly into the fMRI analyses. CVR will be quantified by measuring changes in cerebral blood flow in response to a hypercapnia challenge while monitoring end tidal CO2. Differences in group fMRI activation patterns between young and older adults will be identified with analysis of covariance use the general linear model. This analysis will be conducted with and without incorporating the CVR maps from each subject as a covariate of no interest to determine if differences are associated with changes in neural activity or age-related changes in cerebral blood flow. Specific Aim 2 will determine if a direct correlation exists between age-related reductions in resting CBF and CVR. If a direct correlation exists then the simple measure of resting CBF can replace CVR in Specific Aim1. The successful completion of these two specific aims will allow the question of whether the fMRI results are due to changes in neural activity or changes in blood flow will no longer be an issue. Thus, allowing the more important question “What is successful aging?” to be investigated with confidence and clarity. While this proposal focuses on the effect of age-related changes to the cerebral vascular reserve on fMRI activation maps, the discoveries emerging from this research
have broader applicability to any condition, disease, or drug that affects cerebral blood flow and the cerebral vascular reserve including but not limited to Alzheimer’s disease, Parkinson’s disease, vascular dementia, stroke, caffeine consumption, and alcoholism.

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