The Ketogenic Diet and Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common form of dementia. There are currently FDA-approved symptomatic therapies for AD and a recently approved, potentially disease-modifying drug, Aducanumab; however, there are no curative or preventative therapies. Research suggests that diet may play a role in AD, but it is inconclusive relative to which dietary approach provides the most neuroprotective effects. There are other life-style approaches that have been found to possibly play a role in AD prevention/treatment. These include exercise, brain training, and social interaction. A combined approach may be more effective than any one modality alone. The ketogenic diet (KD) is one specific diet that has been studied vis a vis neurodegenerative diseases. Similar benefits to those of a KD can also be achieved through consuming a normal diet and supplementing with ketogenic agents. The purpose of this review is to compare the methods of inducing hyperketonemia and their impact on AD prevention/treatment, as well as to explore the possible benefits of a combined approach.

METHODS: The PubMed database was searched for clinical trials and randomized, controlled trials involving the KD or exogenous ketone administration and AD. Key search terms used included "ketogenic diet and Alzheimer's disease," "ketosis and Alzheimer's disease," "MCT and Alzheimer's disease," and "exercise and diet and Alzheimer's disease." Only studies involving patients diagnosed with AD were included in this paper, but for the combined approach section, studies included patients diagnosed with MCI due to a paucity of combined approach studies involving AD patients alone.

RESULTS: There is evidence that the KD and exogenous ketone supplementation may provide treatment benefits in AD patients. It is unclear whether one method is better than the other. The specific food composition of the KD should be considered, because certain types of fat sources are healthier than others. Many forms of the KD require strict monitoring of carbohydrate intake, which would often fall under the responsibility of the caregiver. Future studies may be more feasible in an institutional setting, where it would be easier to administer and to monitor a dietary protocol. Exogenous supplementation may be more likely to be adhered to as a long-term treatment, because the dietary changes are not as drastic. A multidomain approach may be the most effective in possibly preventing/delaying AD and in improving/stabilizing and possibly slowing disease progression in those with AD.

CONCLUSION: Most current studies are small, often uncontrolled, and only look at the short-term effects of ketosis on cognition. Large, long-term, randomized, controlled trials relative to the impact of the KD in patients with cognitive impairment and AD are lacking and thus needed. Combined approaches may prove to be more beneficial in possibly preventing/delaying AD and in improving/stabilizing and possibly slowing disease progression in those with MCI or AD. Future research should investigate the effect of additional combined approaches relative to neurocognitive decline in AD patients.