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41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV

Published online by Cambridge University Press:  21 December 2023

Maulika Kohli*
Affiliation:
SDSD/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
Laura M Campbell
Affiliation:
SDSD/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
Erin Sundermann
Affiliation:
UC San Diego, San Diego, CA, USA.
Mark W Bondi
Affiliation:
UC San Diego, San Diego, CA, USA.
Paul Gilbert
Affiliation:
San Diego State University, San Diego, CA, USA.
Donald Franklin
Affiliation:
UC San Diego, San Diego, CA, USA.
Scott Letendre
Affiliation:
UC San Diego, San Diego, CA, USA.
Robert K Heaton
Affiliation:
UC San Diego, San Diego, CA, USA.
Payal Patel
Affiliation:
University of Washington, Seattle, WA, USA.
Susan Morgello
Affiliation:
The Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Benjamin Gelman
Affiliation:
University of Texas Medical Branch at Galveston, Gaveston, TX, USA.
David Clifford
Affiliation:
Washington University in St. Louis, St. Louis, MO, USA
Raeanne C Moore
Affiliation:
UC San Diego, San Diego, CA, USA.
David J Moore
Affiliation:
UC San Diego, San Diego, CA, USA.
*
Correspondence: Maulika Kohli, SDSD/UC San Diego Joint Doctoral Program in Clinical Psychology, mkohli@health.ucsd.edu
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Abstract

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Objective:

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

Participants and Methods:

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results:

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

Conclusions:

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Type
Poster Session 03: Dementia | Amnesia | Memory | Language | Executive Functions
Copyright
Copyright © INS. Published by Cambridge University Press, 2023