Mitochondria are a culprit in the onset of Parkinson’s disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson’s disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10−6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56–0.81) and P = 2.46 × 10−5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson’s disease over time.
Mitochondrial haplogroup is associated with cognitive decline in patients with PD.
This genetic survival study overall indicates that mitochondrial macro-haplogroups are associated with reduced risk of cognitive disease progression in PD. Post hoc analyses identified the haplogroups J, T and U# as the haplogroups associated with reduced risk compared to the macro-haplogroup H in Parkinson’s patients, but further research is required to definitively identify the contribution and statistical significance of each individual haplogroup. Previous meta-analyses found that the haplogroups J, K and T are associated with reduced susceptibility for PD and the haplogroup H is linked to elevated susceptibility for PD.15