Effect Of Apoe Genotype On Prospective Memory In HIV-1

Erin E. Morgan, University of California, San Diego
Basic-Applied Clinical

Given the demonstrated relevance of prospective memory (ProM) to everyday functioning, an investigation of genetic risk factors for HIV-1-associated ProM impairment has crucial implications for HIV-1 seropositive individuals, their caregivers, and the healthcare system. Shown to be impaired in HIV-1 disease, ProM is a novel aspect of episodic memory describing memory for future intentions (i.e., "remembering to remember") that is an important and unique predictor of daily functioning. Regarding the genetic aspects of ProM, a polymorphism of the APOE gene, specifically the APOE ε4 allele, is associated with impaired ProM in healthy adults. In addition, HIV-1 seropositive carriers of the APOE ε4 allele demonstrate a nearly threefold increased risk for HIV-1-associated dementia (HAD). Thus, although the relationships among HIV-1 infection, APOE genotype, and ProM have been demonstrated separately, no study has examined the potentially important interrelationships between these factors, nor the association between APOE genotype and milder forms of HIV- associated neurocognitive impairment. The present study therefore aims to examine the effect of presence of the APOE ε4 allele on ProM performance in HIV-1 infection in a sample of 180 HIV-1 seropositive individuals, with the hypothesis that APOE ε4 carriers will demonstrate greater ProM impairment relative to non-carriers. Hypotheses regarding ProM cue-types (i.e., time- and event-based cues) and exploratory analyses of error types will also be investigated. Moreover, considering that the incidence of frank dementia is declining while milder forms of neurocognitive impairment are increasingly prevalent in HIV-1 disease, it is surprising that the APOE-related risk for developing HIV-1-associated neurocognitive impairment beyond HAD has not yet been characterized. Accordingly, the current proposal also aims to delineate the nature of this relationship, hypothesizing that HIV-1-associated neurocognitive impairment, with specific deficits in episodic memory and executive functioning, will be more prevalent in APOE ε4 carriers versus non-carriers. Further, it is hypothesized that presence of an APOE ε4 allele in HIV-1 seropositive individuals will be related to a higher prevalence of dependence in everyday functioning (i.e., instrumental activities of daily living; IADL). Findings elucidating the association between APOE ε4 status and risk for ProM impairment in HIV-1 disease would provide the basis for further hypothesis-driven investigation into the genetic contribution to HIV-1 neuropathogenesis and development of HIV-1-associated neurocognitive impairment. Understanding this genetic risk could enhance clinical diagnosis of HIV-1-associated neurocognitive impairment, a continued public health concern in the post-HAART era. Moreover, demonstrating the link between APOE ε4 status, ProM impairment, and poorer functional outcomes could inform ProM-focused intervention targets for improving everyday functioning (e.g., IADLs).