The purpose of this FOA with set-aside funds (PAS) is to invite applications to study the biological basis of vascular cognitive impairment (VCI). VCI causes a burden of illness similar to that caused by Alzheimer’s disease (AD), but has been far less well-studied. Recently, however, some important strides have been made in understanding the etiology of VCI. These include the discovery of a monogenic form of vascular dementia, CADASIL, and identification of the causative gene as Notch 3. In addition, MRI and other pathological data have provided a clearer delineation of the various clinical subtypes of VCI, and awareness of the synergistic interaction between vascular and classical Alzheimer’s pathologies in producing cognitive impairment. The goal of this FOA is to build on these first critical achievements to obtain a better understanding of the cellular and molecular mechanisms causing vascular, neural, and glial dysfunction in human VCI and animal models of VCI.