Aging in brain is accompanied by changes in brain vasculature such as increased stiffness of vascular wall and reduced blood supply, potentially important factors in affecting cognition. Furthermore, although functional neuroimaging techniques have provided tremendous insight into the adaptability of the aging brain, the fMRI signal relies upon an indirect signal--changes in oxygenation and blood flow--to detect intensity of neural activation across different sites. It is likely that age differences in vascular health afect blood flow and thereby change fMRI signals independent of the neural changes, which complicates the interpretation of fMRI results. In past three years, we have applied several novel vascular imaging techniques (some developed by the Principal Investigator, Hanzhang Lu) to a lifespan sample of 220 healthy subjects aged 20 to 89 funded under an R-21 award to Hanzhang Lu. The subjects studied were participants in the Dallas Lifespan Brain Study (DLBS) which is funded as a MERIT Award to Denise C Park, examining neural structure and function, as well as cognitive behavior in participants. The cross-sectional data identified Cerebral Vascular Reserve (CVR) as the most age-sensitive vascular parameter, showing a decline that was three times faster than that of resting Cerebral Blood Flow (CBF). The CVR-corrected fMRI data supported the current fMRI literature of an age- related over-recruitment in the frontal cortex, but cautioned that the activation decrease in the occipital lobe and medial temporal lobe may be vascular artifacts. In contrast to our findings, a recent study by Nyberg and colleagues (2010) reached an opposite conclusion based on longitudinal but uncorrected (for CVR) fMRI signals. The present project will therefore focus exclusively on CVR and collect longitudinal, follow-up data in the original cohort (lag of 4 years from initial visit), so that longitudinal, CV-corrected fMRI data will be available. The present proposal builds upon our previous cross-sectional study, which demonstrates the feasibility of the proposed work as well as the experience and excellent collaboration history of our team.
The specific aims of the proposal are: 1. Determine longitudinal changes in Cerebral Vascular Reserve (CVR) in a group of healthy subjects aged 24-93 years. 2. Examine longitudinal fMRI BOLD changes after CVR correction. 3. Examine the extent to which CVR correction can improve the relationship between fMRI signal and cognitive function. The completion of this study will provide one of the most unique datasets in aging literature where cognition, structural, functional, vascular parameters of the brain are collected in the same participants, allowing us to determine in a definitive way the role that cerebrovascular healthy plays in mediating BOLD signal and cognitive function across the lifespan.
An important aspect of brain aging is the microscopic changes of the blood vessels. These changes will affect the brain health by limiting blood supply which is key to the functioning of neurons. In this project, the most age-sensitive vascular parameter, Cerebral Vascular Reserve, will be assessed using advanced MRI technologies and the results will be compared to other aspects of brain and cognitive changes.
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