Abstract
Objective To determine whether virally suppressed HIV neuropathogenesis, a chronic neuroinflammatory state, promotes abnormal brain amyloid deposition.
Methods A total of 10 men with virally suppressed HIV-associated neurocognitive disorder (HAND), aged 46–68 years, underwent 11C-labeled Pittsburgh compound B PET. Data from the Australian Imaging, Biomarkers and Lifestyle (AIBL), including 39 cognitively normal individuals (aged 60–74 years), 7 individuals with mild cognitive impairment (MCI) (aged 64–71 years), and 11 individuals with Alzheimer disease (AD) (aged 55–74 years), were used as reference. Apart from more women, the AIBL cohort was demographically comparable with the HIV sample. Also, the AIBL PET data did not differ by sex. Cerebellum standardized uptake value ratio amyloid values within 22 regions of interest were estimated. In the HIV sample, apolipoprotein E (APOE) was available in 80%, CSF biomarkers in 60%, and 8–10 years of long-term health outcomes in 100%.
Results HAND and the AIBL group with no cognitive deficits had similar amyloid deposition, which was lower than that in both the MCI and AD groups. At the individual level, one HAND case showed high amyloid deposition consistent with AD. This case also had a CSF-AD–like profile and an E4/E4 for APOE. Clinically, this case declined over 18 years with mild HAND symptoms first, followed by progressive memory decline 8–9 years after the study PET, then progression to severe dementia within 2–3 years, and lived a further 6 years. Another HAND case showed increased amyloid deposition restricted to the hippocampi. Two other HAND cases showed abnormally decreased amyloid in subcortical areas.
Conclusions Relative to cognitively normal older controls, brain amyloid burden does not differ in virally suppressed HAND at the group level. However, individual analyses show that abnormally high and low amyloid burden occur.
Glossary
- AAL=
- Automated Anatomical Labeling;
- Aβ=
- amyloid beta;
- AD=
- Alzheimer disease;
- AIBL=
- Australian Imaging, Biomarkers and Lifestyle;
- ANI=
- asymptomatic neurocognitive impairment;
- APOE=
- apolipoprotein E;
- 11C-PiB=
- 11C-labeled Pittsburgh compound B;
- cART=
- combination antiretroviral therapy;
- HAD=
- HIV-associated dementia;
- HAND=
- HIV-associated neurocognitive disorder;
- MCI=
- mild cognitive impairment;
- MND=
- mild neurocognitive disorder;
- MSK=
- Memorial Sloan Kettering;
- NNTC=
- National NeuroAIDS Tissue Consortium;
- PLHIV=
- people living with HIV infection;
- PSP=
- progressive supranuclear palsy;
- PVE=
- partial volume effect;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
All authors are aware of the terms of the AIBL Data Use Agreement. Data used in the preparation of this article were obtained from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) funded by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), which was made available at the ADNI database (loni.usc.edu/ADNI). The AIBL researchers contributed data but did not participate in analysis or writing of this report. See aibl.csiro.au for further details.
- Received October 7, 2019.
- Accepted in final form April 6, 2020.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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