Mitochondrial dynamics-related genes DRP1 and OPA1 contributes to early diagnosis of cognitive impairment in diabetes

Abstract

Background and aim: DRP1 and OPA1 play important roles in mitochondrial fusion and fission. However, the role of DRP1 and OPA1 amplification in mitochondrial cognitive impairment has not been reported. This study aimed to investigate the relationship between DRP1 and OPA1 and the risk of cognitive impairment.

Methods: In this study, 45 elderly patients with diabetes admitted to the Lianyungang Second People's Hospital from September 2020 to January 2021 were included. The patients were divided into normal group, mild cognitive impairment group and dementia group by using MMSE score, and the clinical characteristics of the three groups were compared. The amplification multiples of the two genes' DNA were calculated by ΔΔCT and defined as 2^{- K}. Spearman rank correlation was used to analyze the correlation between the DNA amplification multiples of patients' DRP1 and OPA1 and AD8 and MoCA scores. The sensitivity and specificity of DNA amplification multiples of DRP1 and OPA1 to predict clinical outcomes of diabetic cognitive impairment were evaluated using Receiver operator characteristic (ROC) curves. Multiple logistic regression was used to evaluate the relationship between DNA amplification factor of DRP1 and OPA1 and cognitive function.

Results: DRP1(2^{- K}) and OPA1(2^{- K}) significantly increased and decreased in dementia and MCI groups compared with the normal group (P ≤ 0.001). The DNA amplification factor of DRP1 was positively correlated with AD8 score and negatively correlated with MoCA score (P < 0.001). The DNA amplification factor of OPA1 was positively correlated with the MoCA score (P = 0.0002). Analysis of ROCs showed that the DNA amplification factor of OPA1 had a higher predictive value for dementia (P < 0.0001), and that it had a higher predictive value when used in combination with DRP1. Multiple logistic regression results showed that increased DNA amplification in DRP1 was associated with increased risk of dementia (OR 1.149;95%CI,1.035-1.275), and increased DNA amplification in OPA1 was associated with decreased risk of MCI (OR 0.004;95%CI,0.000-0.251) and dementia (OR 0.000;95%CI,0.000-0.134).

Conclusion: DNA amplification multiples of DRP1 and OPA1 are associated with the risk of dementia in elderly patients and may serve as potential biomarkers.

Keywords: Cognitive impairment; Diabetes; Drp1; Mitochondrial dynamics-related genes; Opa1.