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Fig. 2 | Molecular Neurodegeneration

Fig. 2

From: Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Fig. 2

Ccf-mtDNA levels associate with PD treatment. a CSF ccf-mtDNA levels in treated PD patients are significantly lower than untreated patients (mean ccf-mtDNA in 160 treated PPMI-PD patients 2.1 (95%CI = 1.97–2.14) versus 2.4 (95%CI = 2.12–2.60) in 16 untreated PPMI-PD patients, Student’s t-test p = 0.029, Cohens d = 0.62). b A reanalysis of our previously published data [19], with ICICLE-PD patients now grouped as treated/untreated further supports our findings that treatment affects ccf-mtDNA levels at 0 months (mean ccf-mtDNA in 39 treated ICICLE-PD patients 1.9 (95%CI = 1.77–2.01), versus 2.5 (95%CI = 1.88–3.13) in 3 untreated ICICLE-PD patients, Student’s t-test p = 0.009, Cohens d = 1.9). At 18 months, ccf-mtDNA levels appeared similar between untreated/treated PD patients (n = 4/48, p = 0.36). However, 3 out of the 4 18-month untreated cases were receiving treatment at 0 months (indicated by the arrows), suggesting that the effect of treatment on reducing ccf-mtDNA had already occurred, although this is based on a small subset and should be interpreted with caution. c-d CSF ccf-mtDNA levels are significantly inversely correlated to levodopa effective daily dose (LEDD) in c) PPMI-PD (n = 157, 36 month samples, p = 0.011, r2 = 0.05) and d ICICLE-PD (n = 48, 18 month samples, p = 0.035, r2 = 0.1) patients. Dotted lines indicate 95% CI. e Specific treatment type is significantly associated to CSF ccf-mtDNA levels (ANOVA p = 0.048), with levodopa/carbidopa treated PPMI-PD patients showing significantly reduced ccf-mtDNA levels compared to untreated patients (mean ccf-mtDNA 2.0 (95%CI = 1.77–2.16) in 40 levodopa/carbidopa treated PD versus 2.4 (95%CI = 2.12–2.60) in 16 untreated PD, Dunnett’s p < 0.05, Cohens d = 0.76). CSF ccf-mtDNA levels appear lower in patients treated with combination therapies, although this did not reach statistical significance (Dunnett’s p > 0.05). Where L-dopa = levodopa/carbidopa, DA = dopamine agonist, MAOI = monoamine oxidase inhibitor and Comb = combination of > 2 treatments. f) CSF ccf-mtDNA levels are associated to treatment duration (18 to > 31 months ANCOVA p = 0.018, with treatment type as a covariate), with PPMI-PD patients treated for < 18 months showing a significant reduction in CSF ccf-mtDNA levels when compared to each subsequent time point (Tukey’s corrected P < 0.05 for each time point). Error bars indicate 95% confidence interval (95%CI)

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