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

Robert Krikorian, Marcelle D. Shidler, Suzanne S. Summer, Patrick G. Sullivan, Andrew P. Duker, Richard S. Isaacson, Alberto J. Espay

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalClinical Parkinsonism and Related Disorders
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019


  • Carbohydrate restriction
  • Memory
  • Mild cognitive impairment
  • Nutritional ketosis
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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