How common a problem early Alzheimer's or other forms of senile degeneration might be is unclear, but Dr Valcour described one example of a case he has seen. He was a 67 year old Caucasian male, a retired teacher who lived alone. He complained mostly about memory problems: “typical things like leaving the stove on, getting lost while driving,” said Dr. Valcour.
He had been HIV-infected since the 1980s and his CD4 nadir (74) occurred in the 1990s. When he presented to Dr Valcour, he was on a standard regimen, with a CD4 cell count over 400, viral load was undetectable both in plasma and CSF, and his cholesterol/glucose was under control.
However, they knew from a research protocol that he carried apolipoprotein E4 allele, and both his parents had Alzheimer’s disease in their 70’s and 80’s. His MRI indicated some white matter hyper-intensity that might be mistaken as being HIV-related in a younger person with HIV, but in an older patient with long-standing hypertension would probably be attributed to other causes.
“When you look at his neuropsychological profile over the four years we followed him, he had a striking amount of verbal recall problems, whereby he could only remember four numbers when he started and it decreased over time to the point where he was not recalling any of them."
"He had visual spatial skill abnormalities which really made me think of posterior regions of the brain being affected, both in his recall as well as his visual spatial skill copy, and then he had some of the psychomotor abnormalities that you would expect in group pegboard and so forth - so really a mixed picture."
"But I think it would be very hard for people in this room to just quickly call this HIV-associated dementia. We may be seeing these patients more and more frequently as we follow this epidemic.”
So they looked at the apolipoprotein E4 allele status in a small study and found that 40% (10 out of 25) older HAD participants had at least one E4 allele, compared to 17% (2 out of 12) younger patients with HAD, offering some support for Dr Valcour's suspicion that Alzheimer's may be implicated in the emergence of dementia in HIV-positive people.
Data on abnormal protein deposition which occurs in people with neurodegeneration related to Parkinson's or Alzheimer's disease have been less clear. For instance, there have been some reports of abnormal amyloid deposition (which forms part of the plaques which occur in the brains of people with Alzheimer's) occurring in some patients with HIV — but Valcour has been unable to find any evidence of this in his patients.
“There is a tendency in autopsy material with the increasing age of the individuals for an increased number of lesions that are associated either with Parkinson’s disease or Alzheimer’s disease,” said Dr. Eliezer Masliah of the University of California, San Diego.
“In terms of the disorders associated with Parkinson’s disease, we have seen an increase in accumulation of alpha-synuclein in aging individuals with HIV in the nervous system. We also have observed these very peculiar amyloid deposits as well as these intracellular amyloid immuno-reactive structures associated with HIV in these elderly individuals (older than 50 years old).”
Another researcher, Dr Cristian Achim from the University of Pittsburgh presented imaging studies that detected abnormal protein deposition in the brains of people living with HIV. These commonly included intraneuronal amyloid, extracellular plaques, tau and oligomers. This could be related to disrupted protein processing described by Dr Benjamin Gelman (see related article).
While researchers have not seen anything in the brains of aging people with HIV quite like Alzheimer's in terms of numbers of plaques and types of plaques, this clearly warrants keeping an eye on, as growing numbers of people living with HIV survive into old age.