Various biomarkers indicate risk for development of HIV-associated dementia and for worsening of the condition, according
to a report in the May 1st issue of Neurology.
"Our study shows that there may be no overlap between biomarkers
that can predict the onset of neurodegenerative disease in HIV-infected
patients and markers that are associated with disease progression," Dr.
Norman J. Haughey from Johns Hopkins University School of Medicine,
Baltimore, Maryland told Reuters Health.
Dr. Haughey and colleagues note that traditional biomarkers such as
HIV load in cerebrospinal fluid are less likely to be associated with
HIV dementia nowadays, and others have yet to be identified.
The researchers sought to determine whether changes in sphingolipid,
sterol, and oxidant balance in cerebrospinal fluid are associated with
HIV dementia and can predict changes in the cognitive status. CSF
samples were obtained from 48 patients, who were categorized for
neuropsychological function on three visits.
Accumulations of tocopherol and triglyceride C52 predicted the onset or worsening of dementia, the researchers report.
Patients with inactive dementia had significant increases in
sphingomyelin, compared with sphingomyelin concentrations in patients
with active dementia or no dementia, they found.
In contrast, active dementia was associated with increases in
ceramide, "suggesting that a conversion of sphingomyelin to ceramide is
associated with progression of dementia."
The team writes: "We interpret these findings to indicate that early
in the pathogenesis of HIV dementia, there is up-regulation of
endogenous antioxidant defenses in brain. The failure of this attempted
neuroprotective mechanism leads to the accumulation of sphingomyelin
and moderate cognitive dysfunction. The breakdown of this enlarged pool
of sphingomyelin to ceramide and the accumulation of highly reactive
aldehydes are associated with declining cognitive function."
Dr. Haughey added, "We are currently verifying the use of
sphingomyelins and ceramides to track disease progression and the
effectiveness of therapeutics in ongoing clinical trials for
HIV-dementia and Alzheimer's disease."
Neurology 2007;68:1481-1487.
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