It is difficult to predict who will and who will not develop neurocognitive complications. Clearly, progression of disease is one factor, as the data in Fig. 6 illustrate. However, general markers of disease progression, such as a decrease in CD4 count and an increase in beta-2 microglobulin (a marker of immune activation), are not powerful predictors of future cognitive complications. Plasma viral load is associated with neuropsychological impairment, but measuring the concentration of HIV in the cerebrospinal fluid (CSF) may provide a more specific indicator. For example, Ellis and colleagues reported that in patients with AIDS there was an association between CSF viral load, but not plasma viral load, and likelihood of neurocognitive impairment.
Markers of immune activation in the CSF have also been associated with neurocognitive impairment (e.g., an increase in CSF neopterin and CSF beta-2 micro-globulin). As noted previously, concentration of the
excitotoxic compound quinolinic acid is also elevated in the CSF ofthose with HIV dementia; however, it is not clear whether quinolinic acid is another marker of immune activation or is somehow causally related to the neurocognitive impairment.
In terms of risk factors, contrary to expectation, there is no clear-cut association between injection drug use and heightened risk of neurocognitive complications. Although the rates of neuropsychological impairment tend to be higher among injection drug users generally, there does not seem to be an interaction between drug abuse and HIV status. An exception to this rule may be dependence on central stimulant drugs, especially methamphetamine. Preliminary observations suggest that history of methamphetamine dependence may enhance the likelihood of HIV-associated neurocognitive impairment perhaps because of some commonalities in mechanisms of neural injury that involve excitotoxicity.
There has been speculation that some of the subtle neuropsychological impairment found in HIV-in-fected persons might be due to depression, fatigue, or other nonspecific factors. This matter has received considerable exploration and the overall conclusion is that depression and medical symptoms generally do not explain the neuropsychological impairment. For
Research Definition for HIV Neuropsychological Impairment
Performance at least 1.0 standard deviation below age-education norms in at least two different cognitive areas"
The impairment cannot be explained by comorbid conditions (e.g., substance abuse and medications)
The impairment does not occur solely as part of a delirium (e.g., due to CNS toxoplasmosis, lymphoma, or CMV)
"At least five of the following ability areas must be assessed: attention/information processing, language, abstraction/executive, complex perceptual motor, learning, recall/forgetting, motor skills, and sensory.
example, although depressive symptoms increase with frequency with disease progression, there is not a strong association between such symptoms and the likelihood of finding neurocognitive impairment. Similarly, Heaton and colleagues found that neuropsy-chological impairment could not be explained simply on the basis of fatigue and constitutional symptoms.
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