New research will seek to understand why people who are HIV positive are more susceptible to a progressive cerebrovascular disease that can ultimately give rise to dementia. One of the goals of the research is to identify new ways to prevent the blockages that occur in blood vessels and cause damage in the brain.
The $3.6 million National Institute of Aging-sponsored study will be led by University of Rochester Medical Center (URMC) neurologist Giovanni Schifitto, M.D., M.S., and Sanjay B. Maggirwar, M.B.A., Ph.D., with the Department of Microbiology and Immunology.
While it is estimated that more than 1 million Americans are living with HIV, treatments such as combined anti-retroviral therapies (cART) have transformed the disease into a manageable chronic illness. However, as the population living with HIV ages, the long-term effects of both the infection and treatment have given rise to additional health problems.
One such problem is cerebral small vessel disease (CSVD). While the reason CSVD occurs is not clear and may ultimately be the result of a number of factors, a common mechanism is believed to be inflammation. The new study will examine the interaction of two types of blood cells – platelets and monocytes. When these cells become stuck together and form complexes the resulting blockages can lead to a hardening of the arteries.
The brain in particular is highly susceptible to damage when blood flow becomes impaired due its network of tiny vessels. When complexes of platelets and monocytes accumulate in the brain they can promote inflammation which can cause vessels to become leaky, plugged, or burst, resulting in micro-strokes or micro-hemorrhages that damage neurons and other tissue in the brain.
Cerebrovascular disease is the second leading cause of cognitive impairment and dementia in the general population.
While CSVD can arise due to high blood pressure, diabetes, smoking, and other risk factors, the condition tends to be more prevalent in individuals with HIV. It is estimated that 50-60 percent of people who are HIV positive may develop some form of CSVD by the time they reach their 50s.
The new study will follow 110 HIV positive and 110 healthy individuals for 3 years. Using advanced neuroimaging technologies, URMC researchers will be able to trace blood flow in the brain, determine the integrity of the blood vessels, identify micro-bleeds or ruptured vessels, and measure damage to white matter. Studying these factors over time will enable the researchers to understand the progression of CSVD and potentially identify targets for new therapies.
While this study will examine CSVD in HIV positive individuals, researchers believe that their findings may ultimately be applicable to the general population.
The investigating team includes Meera Singh, Madalina Tivarus, Jianhui Zhong, Henry Wang and Xing Qiu with URMC. The study will be supported by the University of Rochester Center for AIDS Research and the Clinical and Translational Science Institute.