Nutritional ketosis for mild cognitive impairment in Parkinson's disease: A controlled pilot trial

Introduction: Glucose hypometabolism and insulin resistance increase risk for and accelerate progression in Parkinson's disease and neurocognitive disorders. We conducted a proof of concept trial to determine whether ketogenesis, a metabolic adaptation induced by dietary carbohydrate restriction, can improve cognitive performance in Parkinson's disease patients with mild cognitive impairment. Methods: We enrolled patients with mild cognitive impairment associated with Parkinson's disease in an eight-week nutritional intervention with random assignment to either high-carbohydrate consumption typical of the Western dietary pattern (n = 7) or to a low-carbohydrate, ketogenic regimen (n = 7). We assessed changes in cognitive performance as well as motor function, anthropometrics, and metabolic parameters. Results: Relative to the high-carbohydrate group, the low-carbohydrate group demonstrated improvements in lexical access (p = 0.02, Cohen's f effect size = 0.76) and memory (p = 0.01, f = 0.87) and as well as a trend for reduced interference in memory (p = 0.06, f = 0.60). The low-carbohydrate group also exhibited reduced body weight (p < 0.0001, f = 1.89) and increased circulation of beta-hydroxybutyrate (p = 0.01, f = 0.90). Change in body weight was strongly associated with memory performance (p = 0.001). Motor function was not affected by the intervention. Conclusion: Nutritional ketosis enhanced cognitive performance in Parkinson's disease-associated mild cognitive impairment in this pilot study. This metabolic intervention and its mechanisms deserve further investigation in the context of neurodegeneration.