Management of older ( 50 years old) HIV-infected individuals is becoming increasingly complex as many develop multiple HIV-associated-non-AIDS-defining (HANA) comorbidities at an earlier onset. We will utilize frailty measurements and neuropsychological performance (NP) tests to determine if a combination of cognitive impairment and frailty identifies vulnerable older HIV-infected individuals (n=130). In addition, we will employ innovative brain imaging techniques [including arterial spin labeling magnetic resonance imaging (ASL-MRI) and positron emission tomography using Pittsburgh B compound (PET-PiB)] to quantitatively assess perfusion and amyloid deposition in older HIV-infected individuals. We will evaluate if frailty correlates with neuroimaging biomarkers (ASL and PET-PIB) of brain integrity in older HIV-infected patients. Finally, we will determine at three year follow-up if frail older HIV-infected individuals have greater rates of change from baseline in cognitive impairment (NP testing), amyloid deposition (PET-PiB), and perfusion (ASL-MRI) compared to pre-frail or non-frail older HIV-infected individuals. This proposal will place HIV associated changes in frailty and cognition into the mainstream of national brain aging research. We will develop biomarkers that will allow for early detection of changes in brain function at the pre-frail state. It is hoped that these biomarkers will assist in the early administration of tailoed effective interventions.

Public Health Relevance

Contemporary care of older (? 50 years old) HIV-infected patients has become complex and is characterized by the early onset of HIV associated non-AIDS (HANA) conditions. This proposal will: 1) increase our knowledge concerning the interaction between frailty and neuropsychological performance in older HIV-infected individuals; 2) assess the relationship between frailty and neuroimaging markers of amyloid deposition and cerebral blood. These results could assist practitioners in developing early interventions at the pre-frail state to prevent or delay subsequent transition to frailty in older IV-infected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
4R01NR014449-04
Application #
9017820
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Henry, Rebecca
Project Start
2013-05-13
Project End
2018-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Day, Gregory S; Gordon, Brian A; Perrin, Richard J et al. (2018) In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease. Neurology 90:e896-e906
Boerwinkle, Anna; Ances, Beau M (2018) Molecular Imaging of Neuroinflammation in HIV. J Neuroimmune Pharmacol :
Strain, Jeremy F; Burdo, Tricia H; Song, Sheng-Kwei et al. (2017) Diffusion Basis Spectral Imaging Detects Ongoing Brain Inflammation in Virologically Well-Controlled HIV+ Patients. J Acquir Immune Defic Syndr 76:423-430
Mehta, Sanjay R; Pérez-Santiago, Josué; Hulgan, Todd et al. (2017) Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment. J Neuroinflammation 14:72
Wright, Patrick W; Archambault, Angela S; Peek, Stacey et al. (2017) Functional connectivity alterations in a murine model of optic neuritis. Exp Neurol 295:18-22
Clifford, David B (2017) HIV-associated neurocognitive disorder. Curr Opin Infect Dis 30:117-122
Sanford, Ryan; Fernandez Cruz, Ana Lucia; Scott, Susan C et al. (2017) Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era. J Acquir Immune Defic Syndr 74:563-570
Obermeit, Lisa C; Beltran, Jessica; Casaletto, Kaitlin B et al. (2017) Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining ""symptomatic"" versus ""asymptomatic"" HAND. J Neurovirol 23:67-78
Paul, Robert; Rhee, Gina; Baker, Laurie M et al. (2017) Effort and neuropsychological performance in HIV-infected individuals on stable combination antiretroviral therapy. J Neurovirol 23:725-733
Wang, Liang; Benzinger, Tammie L; Su, Yi et al. (2016) Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between ?-Amyloid and Tauopathy. JAMA Neurol 73:1070-7

Showing the most recent 10 out of 45 publications