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Plasma Citrate and Succinate Are Associated with Neurocognitive Impairment in Older People with HIV.
Clin Infect Dis. 2021 Feb 10 [Online ahead of print]CI

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=0.03), 0.07 SD lower time-updated NPZ-4 score (p=0.01), and 0.02 m/s slower time-updated gait speed (p<0.0001). 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≤0.01 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+Show Affiliations

Department of Internal Medicine, Division of Infectious Disease, MetroHealth Medical Center, Cleveland, OH, USA. Case Western Reserve University School of Medicine, Cleveland, OH, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA.Harvard T.H. Chan School of Public Health, Boston, MA, USA.Harvard T.H. Chan School of Public Health, Boston, MA, USA.VA North Texas Health Care System, Dallas, TX; Trinity Health and Wellness Center, Dallas, TX, USA.University of California, San Diego, CA, USA.University of Colorado Anschutz Medical Campus, Aurora, CO, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA. Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.Ohio State University, Columbus, OH, USA.Rush University Medical Center, Chicago, IL, USA.Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA. Cleveland Veterans Administration Medical Center, Cleveland, Ohio, USA.Northwestern University Feinberg School of Medicine, Chicago, IL, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA.Department of Internal Medicine, Division of Infectious Disease, MetroHealth Medical Center, Cleveland, OH, USA. Case Western Reserve University School of Medicine, Cleveland, OH, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33564870

Citation

Hileman, Corrilynn O., et al. "Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 2021.
Hileman CO, Azzam S, Schlatzer D, et al. Plasma Citrate and Succinate Are Associated with Neurocognitive Impairment in Older People with HIV. Clin Infect Dis. 2021.
Hileman, C. O., Azzam, S., Schlatzer, D., Wu, K., Tassiopoulos, K., Bedimo, R., Ellis, R. J., Erlandson, K. M., Kallianpur, A., Koletar, S. L., Landay, A. L., Palella, F. J., Pallaki, M., Taiwo, B., Hoppel, C. L., & Kalayjian, R. C. (2021). Plasma Citrate and Succinate Are Associated with Neurocognitive Impairment in Older People with HIV. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. https://doi.org/10.1093/cid/ciab107
Hileman CO, et al. Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV. Clin Infect Dis. 2021 Feb 10; PubMed PMID: 33564870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma Citrate and Succinate Are Associated with Neurocognitive Impairment in Older People with HIV. AU - Hileman,Corrilynn O, AU - Azzam,Sausan, AU - Schlatzer,Daniela, AU - Wu,Kunling, AU - Tassiopoulos,Katherine, AU - Bedimo,Roger, AU - Ellis,Ronald J, AU - Erlandson,Kristine M, AU - Kallianpur,Asha, AU - Koletar,Susan L, AU - Landay,Alan L, AU - Palella,Frank J, AU - Pallaki,Muralidhar, AU - Taiwo,Babafemi, AU - Hoppel,Charles L, AU - Kalayjian,Robert C, AU - ,, Y1 - 2021/02/10/ PY - 2020/10/20/received PY - 2021/2/10/entrez PY - 2021/2/11/pubmed PY - 2021/2/11/medline KW - citrate KW - human immunodeficiency virus KW - neurocognitive impairment KW - succinate KW - tricarboxylic acid cycle JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis N2 - 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=0.03), 0.07 SD lower time-updated NPZ-4 score (p=0.01), and 0.02 m/s slower time-updated gait speed (p<0.0001). 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≤0.01 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. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/33564870/Plasma_Citrate_and_Succinate_Are_Associated_with_Neurocognitive_Impairment_in_Older_People_with_HIV_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciab107 DB - PRIME DP - Unbound Medicine ER -
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