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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG032872-03
Application #
7919298
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (M1))
Program Officer
Mackiewicz, Miroslaw
Project Start
2008-09-30
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2012-07-31
Support Year
3
Fiscal Year
2010
Total Cost
$214,800
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Adeli, Ehsan; Kwon, Dongjin; Zhao, Qingyu et al. (2018) Chained regularization for identifying brain patterns specific to HIV infection. Neuroimage 183:425-437
Clifford, Katherine M; Samboju, Vishal; Cobigo, Yann et al. (2017) Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years. J Acquir Immune Defic Syndr 76:289-297
Watson, Christa; Busovaca, Edgar; Foley, Jessica M et al. (2017) White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV. J Neurovirol 23:422-429
Zhang, Yong; Kwon, Dongjin; Esmaeili-Firidouni, Pardis et al. (2016) Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification. Hum Brain Mapp 37:4523-4538
Wendelken, Lauren A; Jahanshad, Neda; Rosen, Howard J et al. (2016) ApoE ?4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60. J Acquir Immune Defic Syndr 73:426-432
Guha, Anika; Wang, Liang; Tanenbaum, Aaron et al. (2016) Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. J Neurovirol 22:80-7
Zhang, Yong; Park, Sang Hyun; Pohl, Kilian M (2016) Joint Data Harmonization and Group Cardinality Constrained Classification. Med Image Comput Comput Assist Interv 9900:282-290
Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren et al. (2015) Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort. Neuroimage Clin 9:564-73
Nir, Talia M; Jahanshad, Neda; Busovaca, Edgar et al. (2014) Mapping white matter integrity in elderly people with HIV. Hum Brain Mapp 35:975-92
Greene, Meredith; Steinman, Michael A; McNicholl, Ian R et al. (2014) Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection. J Am Geriatr Soc 62:447-53

Showing the most recent 10 out of 21 publications