The purpose of the proposed study is
to examine the impact of comorbid hepatitis C and HIV infection
on neurocognitive and neuroimaging indices. More than 40%
of HIV patients are co-infected with hepatitis C (Hep C),
and recent studies have suggested that coinfected patients
are at higher risk for neurocognitive difficulties compared
to individuals infected with Hep C alone, or HIV alone (Von
Geissen et al. 2004). To date, only a few studies have examined
the impact of Hep C/HIV coinfection on neurocognitive function,
and these studies have not incorporated neuroimaging to investigate
the relationship between cognitive function and brain morphometric
measures in this population. We will address this issue in
the current study, employing methods previously developed
by members of our team within the CFAR. Specifically, we will
examine neuropsychological functioning and brain MRI indices
in three groups of patients. The first group will include
individuals co-infected with HIV and Hep C (n=10). The second
group will include individuals infected with Hep C but not
HIV (n= 10), and the third group will include individuals
infected with HIV but not Hep C (n=10). All individuals will
be matched on ART history, premorbid intelligence, age, and
substance abuse history.
The neuropsychological tests will include measures sensitive
to HIV-related cognitive impairment including measures of
information processing speed, cognitive flexibility, motor
speed and memory. The neuroimaging protocol will include both
structural indices (whole brain volume, caudate volume and
white matter volume), as well as diffusion tensor imaging
(DTI). DTI is a novel, noninvasive technique to measure the
integrity of subcortical white matter.
Our team of investigators is highly experienced in the use
of the proposed methods and the current protocol will allow
us to obtain pilot data for a RO1 application. Importantly,
the area of study represents a priority funding area for NIDA,
and once these pilot data are obtained we will be in the ideal
position to successfully compete for NIH funding.
Aim 1
Demonstrate significant impairments in cognitive function
among individuals co-infected with HIV and Hep C compared
to individuals infected with HIV or Hep C alone. We expect
co-infected patients will exhibit significant impairments
on measures of cognitive flexibility, information processing
and motor speed compared to the other two groups, but no differences
will be evident between the two comparison groups.
Aim 2
Demonstrate significant changes in neuroimaging indices between
the three groups. We expect reduced caudate volume, whole
brain volume, and white matter volume among the coinfected
group compared to the comparison groups. In addition, we expect
reduced fractional anisotropy and increased mean diffusivity
among the coninfected group on the DTI indices. Finally, the
neuroimaging measures will correlate with performance on the
neuropsychological measures.
Aim 3
Demonstrate a significant relationship between neurocognitive
measures and neuroimaging measures with laboratory markers
of HIV and Hep C viral load.
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