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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
- Maulika Kohli, Laura M Campbell, Erin Sundermann, Mark W Bondi, Paul Gilbert, Donald Franklin, Scott Letendre, Robert K Heaton, Payal Patel, Susan Morgello, Benjamin Gelman, David Clifford, Raeanne C Moore, David J Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 249-250
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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.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
60 Differential Benefits of Internal Strengths and Socioemotional Support on Neurocognition and Daily Functioning Among People with HIV
- Lillian Ham, Maulika Kohli, Dilip V Jeste, Igor Grant, David J Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 56-57
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Objective:
Positive psychological attributes have been associated with better health outcomes and quality of life among people with HIV (PWH). Recently, we identified two latent factors (internal strengths, socioemotional support) among 7 positive psychological attributes through factor analysis (Ham et al., 2022). Depression was inversely associated with both factors. Our current aim was to investigate associations between these latent factors, neurocognition, and daily functioning among PWH.
Participants and Methods:106 PWH and 90 HIV- participants were included in cross-sectional analyses (Mage = 51.3, 77% men, 60% White). Seven positive psychological questionnaires, a neuropsychological battery covering 7 domains, two daily functioning questionnaires (Patient’s Assessment of Own Functioning (PAOFI); Independent Activities of Daily Living (IADL)), and a depression symptom questionnaire (Center for Epidemiologic Studies Depression Scale) were administered. Internal strengths and socioemotional support composite z-scores were calculated using HIV- participants’ scores as reference. Outcomes included global and domain-specific neurocognitive T-scores (demographically-adjusted), global deficit score (GDS), number of functional impairments (PAOFI), and number of functional declines (IADL). Main effects of HIV status, latent factors, and their interaction were included in linear (neurocognition) and Poisson (daily functioning) regressions. Significant interactions were followed up by simple effects analyses and nonsignificant interactions were removed. Depressive symptoms and demographics associated with daily functioning were included as covariates.
Results:PWH exhibited worse neurocognitive performance (global, executive functioning, processing speed, learning, recall, GDS) and reported greater functional difficulties and depressive symptoms compared to HIV-counterparts (ps < 0.05). For neurocognition, there were socioemotional support x HIV status (B = 2.39, p = 0.04) and internal strengths x HIV status (B = 2.70, p < 0.05) interactions on verbal fluency, accounting for depressive symptoms, such that only PWH had a positive association between socioemotional support and verbal fluency (B = 1.97, p = 0.01). Removing nonsignificant interactions, there was a main effect of socioemotional support on global cognition (B = 1.01, p = 0.04) and psychomotor speed (B = 1.83, p = 0.02), independent of HIV status and depressive symptoms. For daily functioning, there was a socioemotional support x HIV status interaction on IADL declines (B = 0.42, p = 0.02), accounting for depressive symptoms and education, such that only HIV- participants had an inverse relationship between socioemotional support and IADL declines (B = -0.64, p < 0.001). Removing non-significant interactions, there were main effects of internal strengths on PAOFI impairments (B = -0.36, p < 0.001) and IADL declines (B = -0.38, p < 0.001), independent of HIV status and depressive symptoms.
Conclusions:Among PWH, both positive psychological factors were associated with better neurocognition, even after adjusting for depressive symptomatology. Though internal strengths were associated with better daily functioning regardless of HIV status, socioemotional support was not related to daily functioning in PWH. While mechanisms underlying these associations cannot be established cross-sectionally, it is possible that among people with medical illnesses complicated by cognitive disturbance, positive psychological factors relate to improved health-related behaviors (e.g., better disease management). Additionally, better neurocognition, including cognitive reserve, may engender greater resilience and improved ability to marshal social support.
Concurrent validity and reliability of at-home teleneuropsychological evaluations among people with and without HIV
- Maulika Kohli, Arin Fisher, Ni Sun-Suslow, Anne Heaton, Matthew S. Dawson, Jennifer Marquie, Donald R. Franklin, Maria Marquine, Jennifer E. Iudicello, Robert K. Heaton, David J. Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 2 / February 2023
- Published online by Cambridge University Press:
- 13 December 2022, pp. 193-204
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Objective:
To determine the reliability of teleneuropsychological (TNP) compared to in-person assessments (IPA) in people with HIV (PWH) and without HIV (HIV−).
Methods:Participants included 80 PWH (Mage = 58.7, SDage = 11.0) and 23 HIV− (Mage = 61.9, SDage = 16.7). Participants completed two comprehensive neuropsychological IPA before one TNP during the COVID-19 pandemic (March–December 2020). The neuropsychological tests included: Hopkins Verbal Learning Test-Revised (HVLT-R Total and Delayed Recall), Controlled Oral Word Association Test (COWAT; FAS-English or PMR-Spanish), Animal Fluency, Action (Verb) Fluency, Wechsler Adult Intelligence Scale 3rd Edition (WAIS-III) Symbol Search and Letter Number Sequencing, Stroop Color and Word Test, Paced Auditory Serial Addition Test (Channel 1), and Boston Naming Test. Total raw scores and sub-scores were used in analyses. In the total sample and by HIV status, test-retest reliability and performance-level differences were evaluated between the two consecutive IPA (i.e., IPA1 and IPA2), and mean in-person scores (IPA-M), and TNP.
Results:There were statistically significant test-retest correlations between IPA1 and IPA2 (r or ρ = .603–.883, ps < .001), and between IPA-M and TNP (r or ρ = .622–.958, ps < .001). In the total sample, significantly lower test-retest scores were found between IPA-M and TNP on the COWAT (PMR), Stroop Color and Word Test, WAIS-III Letter Number Sequencing, and HVLT-R Total Recall (ps < .05). Results were similar in PWH only.
Conclusions:This study demonstrates reliability of TNP in PWH and HIV−. TNP assessments are a promising way to improve access to traditional neuropsychological services and maintain ongoing clinical research studies during the COVID-19 pandemic.
Binge Drinking Relates to Worse Neurocognitive Functioning Among Adults Aging with HIV
- Emily W. Paolillo, Rowan Saloner, Maulika Kohli, C. Wei-Ming Watson, Raeanne C. Moore, Robert K. Heaton, David J. Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 6 / July 2022
- Published online by Cambridge University Press:
- 26 July 2021, pp. 600-610
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Objective:
Given the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.
Method:Participants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV−/Binge+ (n = 23), HIV+/Binge− (n = 55), HIV−/Binge− (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.
Results:HIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV−/Binge− participants (p’s < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p’s > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV−/Binge− participants (p’s < .05).
Conclusions:Results showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.