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DECREASED MYELIN CONTENT AND COGNITIVE PERFORMANCE IN ADULTS WITH PERINATAL HIV
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CROI 2022
Abstract Body
Little is known about the cognitive profile of adults with virally suppressed perinatally acquired HIV (pHIV). Additionally, conventional and diffusion tensor imaging has not identified a robust signature of cerebral white matter injury in HIV and the microstructural pathology occurring in the white matter tracts of individuals with pHIV remains unknown. Myelin water imaging (MWI), a novel imaging modality, quantifies myelin content using differences in relaxation times of water contained in the myelin bilayer and free water. We define the cognitive profile of virally suppressed adults with pHIV and demonstrate the association between myelin water fraction (MWF), a metric of myelin content obtained through MWI, and cognition in our cohort.
Seventeen adults with pHIV (ages 21-36 years, 11 Female and 6 Male), virally suppressed on antiretroviral therapy (ART), underwent an 11-test cognitive battery covering seven domains. Raw scores were adjusted for age, education, sex, and race/ethnicity. Domain specific z-scores were determined using normative data. Cognitive impairment was defined as >1.5 standard deviations below the normative mean in 2 or more domains. Eight participants underwent MWI. A Gradient and Spin Echo acquisition sequence was used for MWI data processing. Global and frontal lobe MWF was compared to 16 historical age and sex matched controls. Correlations were assessed using Spearman rank correlation coefficient.
Ten (58%) adults living with pHIV were cognitively impaired with the lowest scores in the gross motor (average z-score: -2.9) and verbal memory (average z-score: -1.5) domains. Global and frontal lobe MWF was lower in the pHIV cohort compared to matched uninfected controls (mean global and frontal MWF: pHIV: 0.071, 0.051; controls: 0.095, 0.081; p<0.0001). Lower global MWF correlated with worse performance in the executive function domain in adults with pHIV (Spearman r: 0.762, p: 0.037).
Cognitive impairment is common among our cohort of adults with virally suppressed pHIV, particularly in the gross motor domain. This may be due to a legacy effect on motor development as individuals in this cohort were born during a period when access to ART was limited. Our pilot imaging data suggest that decreased axonal myelination may occur in individuals with well controlled pHIV. Given the strong correlation between MWF and executive function scores, this reduction in myelination may be a pathologic substrate of pHIV-related cognitive impairment.
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