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Greater Sensorimotor Deficits and Abnormally Lower Globus Pallidus Fractional Anisotropy in HIV+ Women than in HIV+ Men

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Abstract

Aims

Cognitive impairment may be greater in HIV-positive (HIV+) women than in HIV+ men. Whether sex-specific differences exist in brain microstructure of HIV+ individuals is unknown and was evaluated.

Method

39 HIV+ (21 men, 18 women) and 45 seronegative (SN, 20 men, 25 women) participants were assessed with brain diffusion tensor imaging and cognitive assessments (7 neuropsychological domains). Fractional anisotropy (FA) and mean diffusivity (MD) were measured with an automated atlas in selected brain regions. Group comparisons were assessed with linear mixed effects models, with sub-regions and hemisphere (left/right) as repeated factors for each region.

Results

HIV+ women, but not HIV+ men, were slower than sex-matched SN controls on sensorimotor function (Dominant-hand: interaction-p = 0.007; Non-dominant hand: interaction-p = 0.039). Similarly, only HIV+ women had lower FA in the globus pallidus (GP, interaction-p = 0.011). Additionally, regardless of sex, the HIV+ group had poorer Fluency, Speed, and Attention than SN-controls (p = 0.006–0.008), as well as lower FA and higher MD in multiple brain regions (p = <0.001–0.044). Across all participants, performance on Attention was predicted by uncinate-FA (p < 0.001, r = 0.5) and corpus callosum (CC)-FA (p = 0.038, r = 0.23), while the Speed of Information Processing was predicted by CC-FA (p = 0.009, r = 0.3). Furthermore, faster sensorimotor function correlated with higher CC-FA and uncinate-FA in men but not in women (Sex*DTI-interaction-p = 0.03–0.06).

Conclusions

The relatively poorer sensorimotor function and abnormally lower GP_FA, suggesting lesser neuronal integrity, in HIV+ women demonstrate sex-specific effects from HIV-infection on these measures. These findings may be related to the greater immune activation and neuroinflammation in HIV+ women compared to HIV+ men.

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Acknowledgments

This study was supported in parts by NIH grants: National Institute on Mental Health (R01-MH61427); National Institute on Drug Abuse (2 K24-DA16170; R01-DA03659); National Institute of Neurological Disorders and Stroke (U54-NS56883); National Institute on Minority Health and Health Disparities (G12-MD007601); National Institute on Aging (R01AG034852-09). We are grateful to our research participants, the referral physicians and community providers, in Honolulu, Hawai’i. We also appreciate the meticulous and hard work from the multiple clinical and technical research staff members who assisted in the data collection, and David Greenstein, B.A., for DTI image processing.

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Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 670 W. Baltimore Street, HSF III, Baltimore, MD, 21201, USA

    Hua-Jun Liang, Erin E. O’Connor, Thomas Ernst, Eric Cunningham & Linda Chang

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Thomas Ernst & Linda Chang

  3. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Kenichi Oishi

  4. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA

    Linda Chang

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  1. Hua-Jun Liang
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  2. Erin E. O’Connor
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Liang, HJ., O’Connor, E.E., Ernst, T. et al. Greater Sensorimotor Deficits and Abnormally Lower Globus Pallidus Fractional Anisotropy in HIV+ Women than in HIV+ Men. J Neuroimmune Pharmacol 16, 334–345 (2021). https://doi.org/10.1007/s11481-020-09915-w

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