The association between methylmalonic acid, a biomarker of mitochondrial dysfunction, and cause-specific mortality in Alzheimer's disease and Parkinson's disease

Fangfang Zhan; Gaoteng Lin; Lifang Su; Lihong Xue; Kefei Duan; Longfei Chen; Jun Ni

doi:10.1016/j.heliyon.2024.e29357

The association between methylmalonic acid, a biomarker of mitochondrial dysfunction, and cause-specific mortality in Alzheimer's disease and Parkinson's disease

Heliyon. 2024 Apr 15;10(8):e29357. doi: 10.1016/j.heliyon.2024.e29357. eCollection 2024 Apr 30.

Authors

Fangfang Zhan^{1

2}, Gaoteng Lin³, Lifang Su⁴, Lihong Xue⁴, Kefei Duan⁵, Longfei Chen^{6

7}, Jun Ni^{1

2}

Affiliations

¹ Department of Rehabilitation Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China.
² Department of Rehabilitation Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, China.
³ Department of Urology, The 900th Hospital of Joint Logistic Support Force, Fuzhou, China.
⁴ Department of Neurology, The Affiliated Hospital of Putian University, Putian, 351106, China.
⁵ Department of Geriatric Medicine, Tianjin Medical University General Hospital, Tianjin, China.
⁶ Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, China.
⁷ Department of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China.

Abstract

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the leading causes of death among the elderly. Recent research has demonstrated that mitochondrial dysfunction, which is hallmark of neurodegenerative diseases, is a contributor to the development of these diseases.

Methods and materials: Methylmalonic acid (MMA), AD, PD, inflammatory markers and covariates were extracted from the National Health and Nutrition Examination Survey (NHANES). The classification of the inflammatory markers was done through quartile conversion. A restricted cubic spike function was performed to study their dose-response relationship. MMA subgroups from published studies were used to explore the correlation between different subgroups and cause-specific mortality. Multivariable weighted Cox regression was carried out to investigate MMA and cause-specific mortality in patients with AD and PD. Weighted survival analysis was used to study the survival differences among MMA subgroups.

Results: A non-linear correlation was observed between MMA and AD-specific death and PD-specific mortality. The presence of MMA Q4 was linked to increased death rates among AD patients (HR = 6.39, 95%CI: 1.19-35.24, P = 0.03) after controlling for potential confounders in a multivariable weighted Cox regression model. In PD patients, the MMA Q4 (Q4: HR: 5.51, 95 % CI: 1.26-24, P = 0.02) was also related to increased mortality. The results of survival analysis indicated that the poorer prognoses were observed in AD and PD patients with MMA Q4.

Conclusion: The higher level of mitochondria-derived circulating MMA was associated with a higher mortality rate in AD and PD patients. MMA has the potential to be a valuable indicator for evaluating AD and PD patients' prognosis in the clinic.

Keywords: Inflammation; Methylmalonic acid; Mitochondrial dysfunction; NHANES; Neurodegenerative diseases.