Columbia University Medical Center

Researchers To Identify Clinical Markers In Aids-Related Dementia

Researchers to Identify Clinical Markers in AIDS-Related Dementia. New Venture May Improve Treatment for AIDS-Related Neurological Disorders Columbia University Part of $5.8 million NIH Study

NEW YORK, NY, May 14,1998 — As part of a new research effort to identify treatments for HIV dementia, which affects up to 20 percent of people with AIDS, researchers from the Columbia University College of Physicians & Surgeons will identify clinical markers for AIDS-related neurological disorders. Columbia joins two other leading AIDS research centers in the effort, called the Northeast AIDS Dementia Study (NEADS), which is backed by a five-year grant from the National Institutes of Health.
“This is a neglected area,” says Karen Marder, M.D., principal investigator for one of the Columbia University NEADS projects and associate professor of clinical neurology in the Gertrude H. Sergievsky Center at Columbia-Presbyterian. “Deaths from AIDS have decreased because of protease inhibitors, but it is not known whether these medications, which lower viral load in the blood, affect what is going on in the brain.” HIV dementia is an insidious condition marked by relentless decline in cognitive and functional capabilities. Because it usually strikes in advanced stages of HIV disease, the condition may increase in prevalence as people with AIDS live longer. It is well established that the viral load — the amount of HIV in the blood — is a powerful predictor of the progression of AIDS. To date, no comparable measures have been found for neurological deficits that result from HIV infection. The lack of such measures inhibits clinical care and the development of neuroprotective therapies.

“If a reduction in viral load can reverse or stabilize neurocognitive impairment, this would have tremendous treatment implications,” says Dr. Marder. “Aggressive therapy for these impairments would then be warranted at a stage when cognitive impairment is reversible.” Columbia University and its NEADS partners, Johns Hopkins and the University of Rochester, will establish how plasma viral load is related to the development of AIDS-Related cognitive motor disorder and determine the relationship between viral load and levels of immune-cell activation in three body compartments, the blood, cerebrospinal fluid, and the brain. NEADS plans to recruit 460 patients with advanced AIDS who are at risk for neurocognitive decline; 170 will be from Columbia. The study subjects will be representative of the total HIV population, including men and women of various racial, ethnic, and risk-factor backgrounds.

A substantial body of evidence suggests that neurons are damaged by toxic substances released by activated immune cells, leading to impaired cognition. Thus, say the researchers, it is essential to determine the relationships between viral load and markers of immune-cell activation in the various body compartments and to identify which of these measures best predict neurological decline and functional impairment.

A second project led by Steven Albert, Ph.D, assistant professor of neuropsychology and public heath in the Gertrude H. Sergievsky Center at Columbia-Presbyterian, will address the relationship among HIV load, immune-cell activation, and functional status. “If reducing viral burden does not affect severity of cognitive impairment, then anti-retroviral therapies that reduce viral load may add years of functional disability, rather than well years to patients with neurocognitive deficits,” says Dr. Albert. The project will determine how much cognitive performance must change before patients demonstrate, or report, functional deficits.

“The neurological complications of HIV have been underrated,” adds Dr. Marder, “but they are becoming more and more of a problem because other illnesses associated with HIV are becoming better controlled, People with AIDS are living longer, and that puts them at greater risk to develop neurocognitive problems.” ###

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