Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.

Abstract

BACKGROUND:

Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH.

METHODS:

Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed.

RESULTS:

Median age was 51 (range 40-78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P < .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline.

CONCLUSIONS:

Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.

• Authors: Corrilynn O Hileman, Robert C Kalayjian, Sausan Azzam, Daniela Schlatzer, Kunling Wu, Katherine Tassiopoulos, Roger Bedimo, Ronald J Ellis, Kristine M Erlandson, Asha Kallianpur, Susan L Koletar, Alan L Landay, Frank J Palella, Babafemi Taiwo, Muralidhar Pallaki, Charles L Hoppel
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 73 Issue 3 Pg. e765-e772 (08 02 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 33564870 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Citric Acid
• Succinic Acid

Topics

• Adult
• Aged
• Citric Acid
• Cross-Sectional Studies
• HIV Infections (complications)
• Humans
• Middle Aged
• Prospective Studies
• Succinic Acid