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Medical comorbidities and lower myelin content are associated with poor cognition in young adults with perinatally acquired HIV
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Patel, Payal B.a; Prince, David K.a; Bolenzius, Jacobb; Chen, Petera; Chiarella, Jenniferc; Kolind, Shannond; Vavasour, Irened; Pedersen, Taylora; Levendovszky, Swati Ranea; Spudich, Serenac; Marra, Christinaa; Paul, Robertb
AIDS August 07, 2024
Our findings demonstrate that approximately half of our young adult participants living with virally suppressed pHIV meet criteria for cognitive impairment, demonstrating low scores in the gross motor and verbal memory domains. These deficits may be partially explained by non-HIV related medical comorbidities in addition to the legacy effect of chronic HIV. We also show significant association between regional myelin content and cognition in our cohort. Our findings of lower scores in motor and verbal memory domains are similar to prior published studies of cognition in older adolescents and young adults living with pHIV13,14.
the US-based Pediatric HIV/AIDS Cohort Study found no differences between young adults living with pHIV and age and sex matched peers who were HIV exposed in utero but uninfected (HEU)12 . Of note, both the pHIV and HEU young adult subgroups scored lower than age, sex and race adjusted normative means in the working memory and processing speed domains alluding to the fact that external factors may influence cognition in youth affected by HIV and outweigh the influence of HIV directly on cognition in young adults living with HIV.
Abstract
Objective:
Approximately 40% of adults living with HIV experience cognitive deficits. Little is known about the risk factors for cognitive impairment and its association with myelin content in young adults living with perinatally acquired HIV (YApHIV), which is assessed in our cross-sectional study.
Design:
A prospective, observational cohort study.
Methods:
All participants underwent an 11-test cognitive battery and completed medical and social history surveys. Cognitive impairment was defined as Z scores falling at least 1.5 SD below the mean in at least two domains. Twelve participants underwent myelin water imaging. Neuroimaging data were compared to age and sex-matched HIV-uninfected controls. Regression analyses were used to evaluate for risk factors of lower cognitive domain scores and association between myelin content and cognition in YApHIV.
In this cross-sectional study, participants were recruited for cognitive testing and neuroimaging at two sites in the United States: Seattle, WA (n=12) and New Haven, CT (n=9) between August 2018 and February 2023. Our sample size was determined by convenience sampling due to recruitment limitations for in-person studies related to the COVID-19 pandemic. The Institutional Review Boards of the University of Washington and Yale University approved the study; written informed consent was obtained from all participants.
Results:
We enrolled 21 virally suppressed YApHIV across two sites in the United States. Ten participants (48%) met criteria for cognitive impairment. Participants with any non-HIV related medical comorbidity scored lower across multiple cognitive domains compared to participants without comorbidities. Myelin content did not differ between YApHIV and controls after adjusting for years of education. Lower cognitive scores were associated with lower myelin content in the cingulum and corticospinal tract in YApHIV participants after correcting for multiple comparisons.
Cognitive outcomes
The gross motor domain was the most affected (mean z-score: -2.86), followed by the verbal learning and memory domain (mean z-score: -1.58) (Fig 1). Ten of the 21 participants (48%) met criteria for cognitive impairment. Clinical and demographic variables did not differ between the cognitively impaired and the cognitively normal subgroups.
Participants with one or more vascular comorbidity (current smoker, hyperlipidemia, hypertension, or diabetes) had lower language (p=0.03) and global (p=0.04) Z-scores than participants without vascular comorbidities. Participants with any non-HIV related medical comorbidity had lower cognitive scores in language (p=0.02), verbal memory (p=0.02) and executive function (p=0.02) domains compared to those who did not have a non-HIV related medical comorbidity. Participants who used substances had lower scores in the language domain (p=0.04). In contrast, those who screened positive for depression and/or anxiety on symptom scales or who had a prior history of AIDS did not have poorer cognitive scores in our cohort (Table 2).
Conclusion:
Poor cognition in YApHIV may be exacerbated by non-HIV related comorbidities as noted in older adults with horizontally acquired HIV. The corticospinal tract and cingulum may be vulnerable to the legacy effect of untreated HIV in infancy. Myelin content may be a marker of cognitive reserve in YApHIV.
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