Association between preoperative serum homocysteine and delayed neurocognitive recovery after non-cardiac surgery in elderly patients: a prospective observational study

Zhen-Feng Zhang, Qing-Chun Sun, Yi-Fan Xu, Ke Ding, Meng-Meng Dong, Liu Han, Abdul-Mannan, Yuan Han, Jun-Li Cao, Zhen-Feng Zhang, Qing-Chun Sun, Yi-Fan Xu, Ke Ding, Meng-Meng Dong, Liu Han, Abdul-Mannan, Yuan Han, Jun-Li Cao

Abstract

Background: Homocysteine, folate, and vitamin B12 involved in 1-carbon metabolism are associated with cognitive disorders. We sought to investigate the relationships between these factors and delayed neurocognitive recovery (dNCR) after non-cardiac surgery.

Methods: This was a prospective observational study of patients (n = 175) who were ≥ 60 years of age undergoing non-cardiac surgery. Patients were evaluated preoperatively and for 1 week postoperatively by using neuropsychological tests and were divided into dNCR or non-dNCR groups according to a Z-score ≤ - 1.96 on at least two of the tests. The relationship between the occurrence of dNCR and preoperative levels of homocysteine, folate, and vitamin B12 was analyzed. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with dNCR.

Results: Delayed neurocognitive recovery was observed in 36 of 175 patients (20.6%; 95% confidence interval [CI], 14.5-26.6%) 1 week postoperatively. Patients who developed dNCR had significantly higher median [interquartile range (IQR)] homocysteine concentrations (12.8 [10.9,14.4] μmol/L vs 10.6 [8.6,14.7] μmol/L; P = 0.02) and lower folate concentrations (5.3 [4.2,7.3] ng/mL vs 6.9 [5.3,9.5] ng/mL; P = 0.01) than those without dNCR. Compared to the lowest tertile, the highest homocysteine tertile predicted dNCR onset (odds ratio [OR], 3.9; 95% CI, 1. 3 to 11.6; P = 0.02), even after adjusting for age, sex, education, and baseline Mini Mental State Examination.

Conclusions: Elderly patients with high homocysteine levels who underwent general anesthesia for non-cardiac surgery have an increased risk of dNCR. This knowledge could potentially assist in the development of preventative and/or therapeutic measures.

Trial registration: NCT03084393 ( https://www.clinicaltrials.gov ).

Keywords: Delayed neurocognitive recovery: risk factors; Neurocognitive; Nutrition.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Metabolic relationship between homocysteine, vitamin B12, and folate. CBS, cystathionine β-synthase; MS, methionine synthase; MTHFR, methylenetetrahydrofolate reductase
Fig. 2
Fig. 2
Recruitment, screening, and selection process of the study population
Fig. 3
Fig. 3
Forest plots showing ORs for tertiles of the homocysteine, folate and vitamin B12 levels in dNCR. 1 indicates comparing to tertile of 1st (≤ 9.6 μmol/L); 2 indicates comparing to tertile of 3rd (>8 ng/ml); 3 indicates comparing to tertile of 3rd (> 427 pg/mL). This figure illustrates the unadjusted model (●), adjusted model 1 for age, sex, education and MMSE (▲); and adjusted model 2 for age, sex, education, MMSE, the levels of homocysteine, folate and vitamin B12 (■). Abbreviations: MMSE, Mini Mental State Examination. *P < 0.05

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