A sample size of 30 individuals was calculated to achieve statistical significance (p < 0.05) for a 30% difference between groups, given the +/−10% error in our measurements. For this pilot study, no adjustments were made for multiple comparisons. Unpaired t-tests with correction for unequal variances were used for comparing NAD, ATPmax bioenergetic, and muscle function parameters between the control and PD groups. Sample sizes for the control groups vary for the physiological measurements because not all data were collected for every study or because of the exclusion of data that failed quality control tests as described in the original study [PMC6204600; PMC8282018; PMC8777576]. Sample sizes for the NAD quantitation are more limited due to the more stringent data quality limits necessary to reliably quantify NAD levels from the 31P MRS data. To ensure reliable quantitation of the NAD peaks, we limited our analyses to spectra with a Lorentzian linewidth (full width at half maximum amplitude) for the PCr peak. Deviation from Lorentzian shape and broader linewidths does not affect PCr recovery rate used to calculate ATPmax because this determination relies on changes in the relative peak area.
R was used to conduct the analysis of the correlation between PD symptoms and bioenergetic parameters. A Shapiro-Wilks test was used to determine normality. Square root transformations were completed on non-normally distributed measures. Some Simple linear regressions were conducted for predictors of Leg [NAD+], Leg ATPmax, and Hand ATPmax, outcome measures of UPDRS (parts 1–4 and total), PRO-PD total, and individual items of slowness, constipation, walking, freezing, falling, rising, daily living, motivation, depression, interest, anxiety, fatigue, daytime sleepiness, dyskinesia, tremor, balance, temperature regulation, orthostasis, visual disturbances, insomnia, REM sleep disturbances, dystonia, speech impairment, drooling, stooping posture, memory, comprehension, sense of smell, sexual dysfunction, medication side effects, urinary symptoms, hallucinations, and nausea, and PROMIS quality of life scale individual and total items.
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