Researchers believe they have determined why some HIV-positive patients who are on antiretroviral therapy and show no signs of disease develop serious depression and memory problems. The discovery may pave the way for a test to determine who is at risk for HIV-related depression and other brain difficulties.
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Severe HIV-related dementia is extremely rare in patients who are taking anti-retroviral drugs. But experts say a milder form of brain impairment, which includes depression, and memory and motor difficulties, is common.
"A very high percent of HIV-infected individuals develop neurological disorders that are not half [as] severe as HIV dementia but can be pretty disrupting for these patients," said Alessia Bachis, a neuroscientist and researcher at Georgetown University Medical Center in Washington D.C.
She and her colleagues appear to have uncovered the biological mechanism responsible for the milder brain problems, a development that could eventually lead to a test to determine who is at risk for neurological impairment.
It has to do with a protein growth factor called mature BDNF - short for brain-derived neurotrophic factor - which acts like "food" for brain cells or neurons. While the AIDS virus does not attack brain cells directly, it interrupts the production of mature BDNF, leading to the shortening of neuronal axons and branches which connect one neuron to another. When brain cells lose this ability to communicate through neuronal connections, they die, and brain function decreases.
The discovery stemmed from a 17-year-old, nationwide study involving 130 HIV-positive women. Investigators found when there was less BDNF in the blood, women were at risk for developing brain abnormalities. In the latest research, scientists studying brain samples taken from patients who died of AIDS and who had developed HIV-associated dementia found that the patients' neurons had shrunk and there was a decrease in mature BDNF.
Bachis believes the mechanism that allows the AIDS virus to halt production of mature BDNF offers researchers a target for the development of a compound or molecule to treat cognitive problems and severe depression in people with the disease.
"And this molecule could be given to HIV-infected individuals as part of their daily regimen. So it could be added to the anti-viral medications that they already take," Bachis said.
Researchers believe such a drug has the potential to also benefit elderly individuals and those afflicted with Parkinson's and Huntington's disease, all of whom show mental declines involving the same pathway.
The study by first author Alessia Bachis, lead investigator Italo Mocchetti and colleagues on the mechanism of HIV-associated dementia is published in Journal of Neuroscience.