Neurological

Citrate and succinate levels associated with neurocognitive impairment in elderly HIV patients

In older people with HIV (PWH), higher plasma citrate and succinate levels are associated with neurocognitive impairment (NCI). This comes from a study published in Clinical Infectious Diseases.

There are associations between NCI and monocyte activation in PWH. Activated monocytes accumulate citrate and succinate, both of which can contribute to NCI. In this study, citrate and succinate were isolated from 957 older PWHs using liquid chromatography-mass spectrometry.

The mean age of the participants was 51 years (interquartile range 46-56) and 81% were men. The mean baseline fasting plasma citrate and succinate levels were 10.08 µg / ml (range 0.98-39.91) and 0.92 µg / ml (range 0.01-7.43), respectively.

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In participants with NCI, higher plasma citrate levels were found on entry than in participants without NCI (mean) [standard deviation (SD)] Citrate content: 10.5 [4.19] 𝜇g / ml vs 9.90 [3.65] 𝜇g / ml; P = 0.06). Each 1-SD increase in citrate levels resulted in 1.18-fold (95% CI; 1.02-1.37; P = 0.03) higher adjusted odds for NCI and 0.07-SD resulted in lower neuropsychological NPZ scores 4 test results in fitted models (P = -0.07) 95% CI, -0.13 to -0.02; P = 0.01). This effect was driven by the oldest age quartile.

Plasma succinate levels were also higher in patients with predominant NCI at admission than in patients without NCI (mean) [SD] Succinate level: 0.97 [0.82] 𝜇g / ml vs 0.89 [0.77] 𝜇g / ml; P = 0.03), but the association did not hold after adjustment for clinically relevant covariates (adjusted odds ratio 1.09; 95% CI 0.94-1.26; P = 0.25). The succinate levels in the oldest age quintile showed that every 1 SD increase was associated with lower NPZ-4 scores (P = -16; 95% CI, -0.28 to -0.03; P = 0.02).

High citrate ingress values ​​were also associated with slower walking speeds of 4 meters, and the effect was again altered by age (P = 0.08 for citrate-to-age interaction). Succinate levels were not related to walking speed.

The results of this study are insufficient to determine whether these associations are specific to HIV-associated NCIs or whether these associations reflect changes in mitochondrial function, glycolysis, or other cellular pathways. The ability of this study to identify potential clinically meaningful interactions was limited. The analysis was reinforced by repeated evaluations using validated tests of neurocognitive function.

Investigators concluded: “Fasting plasma [tricarboxylic acid] Cycle metabolites are age-related with cross-sectional and longitudinal measurements of neurocognitive function and gait speed in PWH. “This supports the importance of altered bioenergetic metabolism in NCI and suggests different mechanisms between different age groups, according to the researchers. They add that these metabolites are potential future targets for NCI therapeutics.

Disclosure: Some of the study’s authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the authors’ information, see the original reference.

reference

Hileman CO, Azzam S., Schlatzer D. et al .; ACTG A5322 team. Plasma citrate and succinate are associated with neurocognitive impairment in the elderly with HIV. Clin Infect Dis. Published online February 10, 2021. doi: 10.1093 / cid / ciab107

This article originally appeared on Infectious Disease Advisor

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