Abstract
Rationale
The APOE ɛ4 allele, an established genetic risk factor for late-onset Alzheimer’s disease, has been linked to an increased risk for dementia especially in older individuals with HIV-1 infection. This allele has also been associated with increased memory impairment following oral lorazepam challenge in healthy elderly. Lorazepam and other benzodiazepines are widely prescribed in individuals with HIV-1 infection who are at increased risk for cognitive impairment.
Objective
The aim of this study was to examine if the ɛ4 allele influences lorazepam-induced memory deficits in this population.
Materials and methods
Forty-one non-demented, HIV-1 seropositive adults (15 ɛ4 carriers, mean age = 43.47 ± 8.25; 26 ɛ4 non-carriers, mean age = 46.77 ± 8.56) participated in a double-blind, placebo-controlled crossover design, receiving single acute oral doses of lorazepam 0.5, 1.0 mg, or placebo over three sessions, each 1 week apart. Standardized neuropsychological assessments, including measures of immediate and delayed verbal recall, were conducted at baseline and at 1, 2.5, and 5 h post-drug administration in each condition.
Results
Acute lorazepam administration produced dose- and time-dependent impairments in measures of verbal recall. However, the e4 allele did not modulate these adverse effects. An APOE ɛ4 group by time interaction was also found such that the APOE-ɛ4-positive subjects had significantly better immediate and delayed verbal recall than the negative subjects at baseline assessment, but the groups did not significantly differ at any subsequent time point.
Conclusion
Future studies should clarify the role of ɛ4 in the modulation of drug-induced cognitive toxicity and baseline performance and their relationship to progressive decline, especially in older individuals with HIV-1 infection, a group at increased risk for dementia.
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Acknowledgments
This work was supported in part by grant R01 MH056994 from the National Institute of Mental Health (N.P.).
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All analyses were repeated (not reported here, available upon request) in the subgroup of individuals currently meeting CDC surveillance case definition for AIDS (Center for Disease Control and Prevention 1992; n = 30; 12 ɛ4+/18 ɛ4−). The pattern of findings was replicated.
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Pomara, N., Belzer, K.D., Silva, R. et al. The apolipoprotein E ɛ4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge. Psychopharmacology 201, 125–135 (2008). https://doi.org/10.1007/s00213-008-1253-1
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DOI: https://doi.org/10.1007/s00213-008-1253-1