Effect of ketones on brain metabolism: Role of MCTs

ABSTRACT

Brain energy metabolism declines with advancing age and to a greater extent in certain neurodegenerative diseases of aging. This reflects changes in mitochondrial function, and manifests as well as declining brain glucose utilization. Relevant changes are evident through direct analyses of mitochondria from the brains of aging individuals and those with Alzheimer’s disease and its frequent syndromic precursor, mild cognitive impairment. Biomarker tests such as fluorodeoxyglucose positron emission tomography further demonstrate such changes.

Although the underlying basis for these phenomena remains unclear, declining brain energy metabolism may contribute to disease-specific neuropathology and represent a therapeutic target. For these reasons, manipulating brain energy metabolism to treat diseases like Alzheimer’s disease mild cognitive impairment are worth exploring. As ketone bodies support brain bioenergetics and ketogenic interventions already feature in the treatment of neurologic disorders, such approaches warrant consideration. This presentation discusses the rationale, as well as past and recent supporting data, for neuroketotherapeutic interventions in Alzheimer’s disease, mild cognitive impairment, and other neurodegenerative diseases. The presentation will especially focus on the rationale for and impact of one particular neuroketherapeutic intervention, the ketogenic diet, on the underlying neurodysfunction and cognitive performance of persons with
Alzheimer’s disease and mild cognitive impairment. Preclinical data from mice placed on a ketogenic diet show a profound impact on molecular pathways implicated in Alzheimer’s disease, and indicate the diet may counteract some of those molecular changes. Human pilot studies also report persons with Alzheimer’s or mild cognitive impairment showed improved cognitive test scores after initiating a ketogenic diet and achieving ketosis. Despite these encouraging data from preclinical and pilot studies, it is important to keep in mind ketogenic diets a‚ect molecular physiology in multiple ways as they also alter systemic insulin levels and inflammation signaling. Adopting a ketogenic diet also requires a considerable lifestyle commitment, which supports the premise of developing alternative neuroketotherapeutic approaches that may potentially benefit persons with Alzheimer’s disease and mild cognitive impairment.

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