he purpose of this application is to elucidate the interaction of HIV infection and alcohol use disorders on central nervous system morbidity and the additional complications of aging arising from extended longevity afforded by advances in anti-HIV pharmacotherapies. Adding to this aging HIV-infected cohort are the increasing numbers of people over 50 years old who are being newly infected. Even in relatively healthy individuals, the aging brain is increasingly vulnerable to endogenous and exogenous insult, an example being the age-alcoholism interaction on brain tissue volume and integrity. Similarly, age-related decline in neural system integrity can compound the HIV-vulnerable brain systems and increase liability for dementia. Further compounding the picture of HIV infection is the common comorbidity of hepatitis C infection (HVC) and the sequelae of AIDS-defining events. Thus, investigation of interactions of normal aging, alcohol use disorders, and HIV infection is now especially germane given the aging HIV-infected population. The proposal builds on our research to date that includes individuals in four groups [HIV + Alcoholism (HIV+ALC), HIV without Alcoholism (HIV), Alcoholics (ALC), Normal Control Subjects (NCS)], examined upwards of 5 times over 8 years with multimodal neuroimaging [structural MRI and diffusion tensor imaging (DTI)], clinical and behavioral assessment, and neuropsychological testing. Results of our analyses demonstrate that the aging brain is highly sensitive to the combined effects of HIV/AIDS, alcoholism, and HCV infection. We now propose to follow our existing longitudinal cohort of over 100 participants (more than half of whom are now over 50 years old) and to recruit an additional 100 individuals age 50 or older who will be followed at 18-month intervals with neuroimaging [MRI, DTI, resting state MRI (rsMRI), and cerebral perfusion measured with pulsed-continuous arterial spin labeling (PCASL)], clinical, neuropsychological, and clinical assessment, including determination of circulating proinflammatory cytokine levels.
Aim 1 : Establish the pattern of brain pathology with MR imaging and functional measures in an expanded sample of older individuals with HIV infection and the combined morbidity of alcohol abuse. Cross-sectional hypotheses predict a complex pattern of additive and interactive effects.
Aim 2 : Assess longitudinal disease trajectory (progression or effective control) as modulated by alcohol abuse, HCV infection, and ART compliance by testing the current and new cohorts at 18-month intervals.
Aim 3 : Establish cross-sectional and longitudinal within-subject relationships among neuroimaging measures, cognitive and motor performance, and clinical status. !

Public Health Relevance

Aging, alcoholism, HIV/AIDS, and the common comorbidity of hepatitis C infection each has deleterious effects on brain structure, function, and quality of lif. With improved medication HIV infected individuals are living into older age, and there is an increase in the number of people who become newly infected with HIV after they are over 50 years old. The proposed study will use longitudinal neuroimaging to identify brain insults underlying the interaction of HIV infection and alcohol abuse with aging and explore how they contribute to the deterioration in clinical, cognitive, and motor abilities in the context of the ultimate frailty of old age.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Matochik, John A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sri International
Menlo Park
United States
Zip Code
Zahr, Natalie M (2018) The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity. Front Aging Neurosci 10:56
Adeli, Ehsan; Kwon, Dongjin; Zhao, Qingyu et al. (2018) Chained regularization for identifying brain patterns specific to HIV infection. Neuroimage 183:425-437
Sullivan, Edith V; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. JAMA Psychiatry 75:474-483
Pfefferbaum, Adolf; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. Biol Psychiatry Cogn Neurosci Neuroimaging 3:844-859
Park, Sang Hyun; Zhang, Yong; Kwon, Dongjin et al. (2018) Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals. Sci Rep 8:8297
Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2017) Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders. Neuropharmacology 122:189-200
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
Fama, Rosemary; Sullivan, Edith V; Sassoon, Stephanie A et al. (2016) Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity. Alcohol Clin Exp Res 40:2656-2666
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
Nichols, B Nolan; Pohl, Kilian M (2015) Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community. Neuropsychol Rev 25:356-68

Showing the most recent 10 out of 38 publications