The coming problem of HIV-associated Alzheimer's disease

Abstract

Background: Dementia associated with human immunodeficiency virus (HIV) is a subcortical neuropathology that does not resemble Alzheimer's disease. However, several lines of evidence suggest that in the future there may be significant numbers of long-term HIV survivors with true Alzheimer's disease. Age is itself a risk factor Alzheimer's disease, and an aging population and widespread use of highly active antiretroviral therapy (HAART) means more elderly HIV patients. Immune reconstitution inflammatory syndrome, lypodystrophic effects of HAART medications, HIV-induced amyloid deposition and excitotoxic effects of gp120 and TAT protein all could be risk factors for subsequent Alzheimer's disease. Finally, HIV patients will have greater vulnerability to common non-HIV pathogens that may contribute to development of Alzheimer's disease.

Presentation of the hypothesis: It is predicted that in the future there will be seen measurable numbers of long-term HIV survivors on HAART who have Alzheimer's disease, with a cortical deficit profile on neuropsychological tests, pronounced cerebral atrophy seen on brain MRI, and neurofibrillary tangles, senile plaques and neuronal loss in post-mortem brain tissue. VALIDATING THE HYPOTHESIS: The hypothesis could be validated through case reports, longitudinal clinical studies, brain bank programs and animal models.

Implications of the hypothesis: Management of HIV may become more difficult, requiring greater provisions for long-term care of HIV patients with chronic dementia. However, it may be possible to reduce or prevent HIV-associated Alzheimer's disease through early use of cholinesterase inhibitors, glutamate-blocking drugs, insulin sensitizing agents, statins and anti-oxidants.