For the problems with dementia, most researchers blame HIV itself

For the problems with dementia, most researchers blame HIV itself, which it turns out can continue replicating in, and damaging, the brain despite being controlled in the bloodstream. Dr. Scott Letendre from the University of California, San Diego, tested spinal-fluid samples from patients who had undetectable levels of virus in their blood. Over a quarter of them tested positive for viral activity in the fluid that surrounds the brain. It turns out that some drug combinations are not as good as others in penetrating the blood-brain barrier. This finding sounded an alarm for AIDS doctors to pay closer attention when prescribing.

But in many cases of dementia, there are no signs of viral activity around the brain, suggesting other factors may be at play. At the Manhattan HIV Brain Bank at Mount Sinai, researchers have dissected the skull contents of 250 volunteers who agreed to a series of psychological interviews and neurological exams, then promised to hand over their brains at death. (One is the gift of Fred Gormley, a felicitous writer who toiled with me years ago at the now-defunct New York Native; he wrote about his life as a brain donor before his death from AIDS complications in 2002.) According to Dr. Susan Morgello, who directs the lab, most people who showed signs of dementia while alive do not have evidence of HIV in their autopsied brain. What they do have in common, she says, is evidence of persistent inflammation, which alone could account for the cognitive damage.

But Morgello is investigating something that’s both more surprising and less so: The inflammation might be caused as much by the patient’s emotional and psychiatric burden as the virus’s pathological course. “We have screamingly high rates of major depressive disorders, substance abuse and dependency, and post-traumatic-stress disorder,” she says of the Brain Bank donors. “About 40 percent of our patients have major depressive disorders when they come to the study. Substance abuse and dependency, that’s a continually moving target, but when we run urine toxicologies, about 30 percent contain illicit substances,” she says. These multiple “insults to the brain” are enough to cause the entire upswing in dementias, she says. But she admits she’s only speculating. “I wouldn’t even say we have 50 percent of the answer here,” she says.