PROJECT SUMMARY Overview: This application is being submitted in response to PA-20-272 "Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)”. The purpose of this administrative supplement to R01 AG066910, entitled “The POINTER Neurovascular Ancillary Study” is to ensure that appropriate transcranial Doppler (TCD) ultrasound equipment and related supplies are available at all 5 participating sites in order to facilitate assessment of cerebral autoregulation and vasomotor reactivity. Participating sites include Wake Forest School of Medicine, Rush University, Advocate Health Care, University of California at Davis (UC Davis), and Rhode Island. The background/significance, specific aims/hypotheses, and approach (including experimental procedures, sample size, power estimates, and analytic plan) have not changed since the original application (i.e., no new science is being proposed). The present supplement will ensure robust and consistent data collection, enhanced quality control, and improved data harmonization across sites. Summary of Parent Grant: The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER) – Neurovascular Ancillary Study (POINTER-NV) will leverage the rich resources and infrastructure of the parent study U.S. POINTER, an ongoing multi-center randomized clinical trial designed to investigate whether randomization to one of two lifestyle interventions that differ in format and intensity alters cognitive trajectory over 2 years in 2,000 older adults aged 60-79 years. POINTER- NV will comprehensively assess autonomic function, cerebral autoregulation, and vascular structure and function by evaluating aortic, carotid, and cerebral hemodynamics using complementary techniques under a variety of conditions. These neurovascular outcomes will be assessed at baseline, Month 12, and Month 24 in 500 POINTER participants across 5 clinical sites. The primary aim is to assess the effects of the POINTER lifestyle intervention on cerebral autoregulation and baroreflex sensitivity. We will also assess intervention effects on aortic stiffness, carotid stiffness, and cerebral vasomotor reactivity. In addition, POINTER-NV will examine whether these neurovascular outcomes are associated with cognition (assessed every 6 months as part of the parent trial) and brain structure and function (assessed every 1-2 years as part of a Brain Imaging ancillary study). Rationale for Administrative Supplement: The proposed administrative supplement will offset unforeseen costs related to the use of TCD in POINTER-NV. Although discussed in the original application, after confirming details of site-specific equipment available, it has come to our attention that Wake Forest is the only clinical site that has the ability to conduct the type of TCD monitoring needed for the cerebral autoregulation and vasomotor reactivity outcomes. This unforeseen cost was unantic...