Falling platelet levels in the blood may predict the onset of HIV-associated dementia six to 12 months later, US researchers report in the September issue of Archives of Neurology.
Platelet levels were tracked in humans following the observation that platelet levels fell sharply in macaques infected with SIV prior to the development of moderate to severe central nervous system disorders.
Thrombocytopenia – a chronic shortage of platelets in the blood – is typically seen in around 10% of untreated HIV-positive people, and can lead to frequent bruising, and in more severe cases, internal bleeding. Up to one five cases are self-correcting without treatment.
Researchers speculate that platelet loss may stimulate the release of thrombopoietic growth factors that have a disruptive effect on the microenvironment of the central nervous system, leading to faster deterioration and rapid onset of dementia.
The North East AIDS Dementia Cohort recruited 396 HIV-positive individuals from 1998 onwards who had advanced HIV infection (CD4 below 200 cells/mm3, or CD4 below 300 with evidence of neurocognitive impairment), and carried out neurological and functional tests every six months.
The analysis was based on 146 subjects (excluding those from the cohort diagnosed with dementia at baseline, 60 who developed dementia during the first year and 49 patients lost to follow-up).
The high rate of dementia onset seen in this cohort was due to the recruitment criteria for the study, and does not reflect the typical incidence of HIV dementia. Approximately 5% of AIDS-defining illnesses in the United States were cases of HIV dementia in 2001-2002.
Participants had an average age of 42, had been infected for an average of seven and a half years, and had an average CD4 cell count of 129 cells/mm3. Seventy-eight per cent were taking antiretroviral therapy, of whom 21% had undetectable viral load. Seventeen per cent had viral load above 100,000 copies/ml at baseline. The baseline average platelet count was 192 x 103/uL.
Just under half (44%) of the evaluable group had mild cognitive or motor disorder on entry to the study, and 27% of participants developed HIV dementia during the median follow-up period of 31 months. Having MCMD at baseline was associated with a twofold greater risk for the subsequent development of dementia (p=0.03).
College-level education showed a trend towards having a protective effect; it was associated with a 48% reduction in the risk of dementia (p=0.08) when compared with education to high school level or below.
There was also a trend towards an increased risk of dementia in individuals with concurrent HIV-related illness (p=0.08).
Platelet decline of greater than 21 x 103uL was associated with a twofold increase in the risk of dementia.
“Analyses indicated that decline from baseline platelet levels was associated with a five- to six-fold increased risk of dementia during the first two years of follow-up, but it was not associated with an increased risk of dementia after two years,” the authors said. “It is possible that individuals who do not progress rapidly to neurologic compromise differ in respect to immune activation, treatment adherence or virologic control relative to those who develop dementia more rapidly.”
The authors say that further study will be necessary in order to validate the use of platelet count as a predictor of the risk of HIV dementia.