Beyond MIND and Mediterranean Diets: Designing a Diet to Optimize Parkinson's Disease Outcomes.

: A growing body of evidence suggests that diet can modify Parkinson's disease (PD) outcomes, although there is disagreement about what should be included and excluded in such a diet. Existing evidence suggests that adherence to the MIND and Mediterranean (MEDI) diets are associated with reduced PD symptoms, but only a few variables from the adherence scales are responsible for the statistically observed improvement. : The goal was to use patient-reported outcomes in a large cohort to identify the foods and dietary patterns (PRO diet) most strongly associated with the fewest PD symptoms over time, and to develop a composite adherence scale to enable comparisons between MEDI, MIND, and PRO. : Data were obtained from the prospective longitudinal natural history study and from Modifiable Variables in Parkinsonism (MVP)-a study designed to identify behaviors associated with patient-reported outcomes (PRO-PD). Upon the completion of the binary and food frequency data collection, using various predictive models and considering congruence with historical data, the PRO diet was created via an iterative process. Our goal was to create a new scale and compare its performance to the existing MIND and MEDI scores. The comparison was made at baseline, using the regression models for PRO-PD and the different scales as the predictors. The models were compared via the Akaike Information Criterion (AIC). To examine whether baseline adherence levels predicted subsequent symptom trajectories, the baseline PRO diet adherence and subsequent slope of progression were evaluated. : Data from 2290 individuals with PD were available for this analysis. The Mediterranean and MIND diets showed almost identical effects. For both the diets, the effect they had on non-motor symptoms was about twice the effect on motor symptoms. The slopes for the total PRO-PD for MEDI, MIND, and PRO-21 were -64.20467, -64.04220, and -28.61995, respectively. The AIC value differences were substantial (>2), indicating meaningful improvements in the model fit for total PRO-PD, as follows: MEDI: 28,897.24, MIND: 28,793.08, and PRO-21: 27,500.71. The subset of individuals who were most adherent to the PRO-21 diet at baseline had the slowest subsequent progression, as measured by a 43% reduced PRO-PD slope, compared to the less adherent groups. : The PRO-21 outperformed the MIND and MEDI diets in the model fit, overcoming the ceiling effects and showing orders of magnitude and superior explanatory power for variance in PD outcomes, despite the smaller per-unit effect sizes. However, its rigorous demands may introduce barriers related to cost, feasibility, and sustainability, underscoring the need for future intervention trials to assess real-world feasibility, adherence, side effects, and clinical impact.