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. Highlights
• The ketogenic group showed improved executive ability and memory.

• No effect of the intervention on motor function

• Change in body weight was strongly associated with cognitive benefit.


Abstract
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.