This research project is proposed in response to the small grants program announcement of the National Institute on Aging (PAR-03-056). Specifically, we respond to the aims #2 (Cardiovascular and Cerebrovascular Aging), and #16 (Executive Function) on the list of objectives in that announcement. The main goal of the proposed research is to explore the feasibility of using Transcranial Doppler Sonography (TCD) for assessment of the influence exerted by hemodynamic factors on differential age related changes in brain and cognition. We are specifically interested in exploring the links between age-related slowing of cerebral arterial blood velocity (CBF-V) in anterior and middle cerebral arteries, as a marker for cerebral hypoperfusion, and regional increase in white matter hyperintensities (WMH) burden as well as shrinkage of the cortex and the underlying white matter. In cognitive domain we will focus in the executive functions which are differentially sensitive to aging and prefrontal pathology. Our hypotheses are based on the body of clinical and preclinical studies that suggested CBF-V slowing as risk factor for developing WMH, our own studies that support the plausibility of modifying influence of cerebrovascular risk factors on age-related brain shrinkage and on the studies that suggest differential vulnerability of executive functions to mild hypertension. While a preliminary report [5] indicates that reduced CBF-V may be associated with structural brain pathology (global WMH burden), neither regional specificity, nor cognitive relationship nor longitudinal course of that index have been established. We have conducted research on a cohort of healthy adults (age 18-85) and obtained cognitive and MRI-based structural brain measures on more than 100 individuals. In this project, we propose to use these data as baseline measures in a two-year longitudinal study and to relate hemodynamic variables to the rate of neuroanatomical and cognitive change. Thus, the proposed research fits the announced goals of the program in that it represents a pilot study that will examine feasibility of application of a technique widely used in the clinic to research on healthy aging, and it will benefit from statistical analysis of existing data. ? ?
