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The relationship between synaptodendritic neuropathology and HIV-associated neurocognitive disorders is moderated by cognitive reserve

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Abstract

We examined whether cognitive reserve moderated the relationship between neurodegeneration and cognition in 67 postmortem persons with HIV (PWH) who were cognitively assessed within 1 year of death. Cognitive reserve was measured via the Wide Range Achievement Test-4 reading subtest (WRAT4). Synaptodendritic neurodegeneration was based on densities of synaptophysin and microtubule-associated protein 2 immunohistochemical reactivity in frontal cortex, and categorized as minimal, moderate, or severe (tertile-split). T-Scores from 15 cognitive tests were averaged into a global cognitive T-score. Among those with low cognitive reserve (based on WRAT4 median split), the moderate neurodegeneration group showed cognition that was poorer than the minimal neurodegeneration group and comparable to the severe neurodegeneration group. Among those with high cognitive reserve, the moderate neurodegeneration group showed cognition comparable to the minimal neurodegeneration group and better than the severe neurodegeneration group. High cognitive reserve may buffer against cognitive impairment among PWH with moderate, but not severe, neurodegeneration.

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Data availability

Biospecimens and clinical data collected as part of the NNTC protocols are available from the NNTC by request. Selected clinical data variables are available through the NNTC Query Tools to help requestors shape data and tissue requests and identify subpopulations of interest. Additional clinical data, beyond what is available from the Query Tools, is available from the NNTC cohorts and can be requested from the NNTC using the Data Request Application. Specimens or data obtained from the NNTC cannot be distributed to third-party companies or institutions without prior consent from the NNTC Steering Committee.

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Funding

Primary funding supporting this study was from R01 MH096648 (MPIs: Levine and Moore). Additional funding was provided from the following National Institutes of Health awards: P30 MH062512, N01 MH22005, HHSN271201000036C and HHSN271201000030C, U24 MH100928, and T32 DA031098. The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30 MH062512 from NIMH.

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Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, La Jolla, CA, 92037, USA

    Arin Fisher, David J. Moore, Ben Gouaux, Virawudh Soontornniyomkij & Erin E. Sundermann

  2. Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA

    Andrew J. Levine

  3. National Institute On Aging, Bethesda, MD, USA

    Eliezer Masliah

  4. Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Scott Letendre

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  1. Arin Fisher
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Fisher, A., Moore, D.J., Levine, A.J. et al. The relationship between synaptodendritic neuropathology and HIV-associated neurocognitive disorders is moderated by cognitive reserve. J. Neurovirol. 29, 713–722 (2023). https://doi.org/10.1007/s13365-023-01177-5

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