Blood Levels of Circulating Methionine Components in Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-analysis

Background: Circulating methionine components have been reported to be associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI), although outcomes are not always consistent.

Materials And Methods: Database searching was conducted using PubMed, Embase, Cochrane Library, and Web of Science from inception to 26 December 2021. In this study, two reviewers independently identified eligible articles and extracted the data. We used Joanna Briggs Institute (JBI) Critical Appraisal tools to assess the overall quality of the included studies. STATA software was employed to perform meta-analysis evaluating the standardized mean difference (SMD) with its 95% confidence intervals (CIs) using random-effects models. Evidence quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.

Results: Totally, 30 observational studies were eligible for inclusion. Compared with cognitively normal controls, patients with AD had increased homocysteine (Hcy) levels in the blood [standardized mean difference (SMD) = 0.59, 95% confidence interval [CI]: 0.36-0.82, = 0.000], plasma (SMD = 0.39, 95% CI: 0.23-0.55, = 0.000), and serum (SMD = 1.56, 95% CI: 0.59-2.95, = 0.002). Patients with MCI were not significantly different from controls (SMD = 0.26, 95% CI: -0.07-0.58, = 0.127). Patients with AD or MCI did not significantly differ from controls of blood vitamin B levels, AD (SMD = -0.05, 95% CI: -0.19-0.08, = 0.440), or MCI (SMD = 0.01, 95% CI: -0.16-0.17, = 0.94). Some cohort studies have suggested that higher Hcy, methionine, and -adenosylmethionine levels may accelerate cognitive decline in patients with MCI or AD, and vitamin B deficiency is a risk factor for the disease; however, the results of other studies were inconsistent. According to the GRADE system, all these outcomes scored very low to low quality, and no high-quality evidence was found.

Conclusion: Only Hcy levels in the plasma and serum were found to be inversely related to the risk of AD. However, due to the low quality of supporting these results, high-quality studies are needed to verify these findings.

Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022308961.