The number of HIV patients who are over 60 years of age is rapidly increasing in the US and will likely represent a geriatric population for which there are limited scientific data to direct care in the next decade. These substantial HIV demographic changes, largely driven by long-term survival due to potent treatment;will require new guidelines to direct optimal care and greater emphasis on well-designed hypothesis-driven research initiatives to direct these guidelines. This application aims to determine the relative impact of increased cerebrovascular disease (CVD) risk factors on cognition in a population of HIV patients over 60 years of age with a long-term goal of determining the extent to which CVD and Alzheimer's disease (AD) interact to impact cognitive health in aged HIV patients. Our hypotheses are driven by previous work identifying an age-associated increased risk for dementia in HIV, an increased risk for dementia associated with diabetes among older HIV patients, and preliminary support that CVD risk factors may impact white matter integrity and cognition in aged HIV patients. When considered in the context of recent discoveries describing abnormal accumulation of amyloid in HIV and the recognized age-associated risk of AD and CVD, there is compelling evidence that interactions among AD, CVD and HIV may accelerate cognitive abnormalities in the oldest HIV patients. Specifically, this application will add structural quantitative MRI and Diffusion Tensor Imaging (DTI) at high field (4.0 Tesla) to a longitudinal cohort of fifty HIV patients over 60 years of age to determine the relative impact of CVD risk factors on changes in white matter integrity and to determine the extent to which changes in white matter integrity impact cognitive performance. While completing this highly relevant research, the candidate will strengthen his clinical skills in the differential diagnosis of cognitive disorders of aging with particular emphasis on potential interactions with HIV and learn the neuroimaging techniques required for quantitative structural MRI analyses and DTI. A combination of clinical mentor (Bruce Miller MD, primary), neuroimaging mentor (Michael Weiner MD, secondary), and the remarkable environment of the Memory and Aging Center at UCSF are highly likely to result in transition to independent researcher.
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