When managing Alzheimer’s disease, most of the pharmacotherapy options target the symptoms of the disease. Recent randomized, controlled trials (RCTs) have analyzed the effect of ketogenic therapies on delaying the progression of the disease and improving cognitive function. A systematic review evaluated the available data on ketogenic therapy and its effect on patients with Alzheimer’s disease and mild cognitive impairment. The researchers concluded that while the research is still in its early stages, ketogenic therapy may hold promise for this patient population.
The study authors queried PubMed, CENTRAL, clinicaltrials.gov, and gray literature for RCTs through April 1, 2019. Eligible studies were published in English and compared the effects of ketogenic therapy versus placebo, usual diet, or meals lacking ketogenic agents on mild cognitive impairment and/or Alzheimer’s disease in adult patients.
Ten RCTs met the eligibility criteria. Interventions were heterogeneous and ranged from 45 to 180 days. They included adherence to a ketogenic diet, intake of ready-to-consume drinks, medium-chain triglyceride (MCT) powder for drinks preparation, yogurt enriched with MCTs, MCT capsules, and ketogenic formulas/meals. Regardless of whether the interventions were acute or long-term, keto neurotherapeutics were correlated with improved general cognition per the Alzheimer’s Disease Assessment Scale-Cognitive. Long-term interventions were associated with improved episodic and secondary memory. Improvements were not observed in psychological health, executive ability, or attention. A correlation was observed between increase in blood ketone concentrations and the neurocognitive battery. Improvements were observed in cerebral ketone uptake and utilization, per the global brain cerebral metabolic rate for ketones and [11C] acetoacetate. APOE ε4(+) and APOE ε4(−) patients presented differing ketone concentrations and cognitive performance; APOE ε4(+) patients had a delayed response, while APOE ε4(−) patients had an improved response.
“Although research on the subject is still in the early stages and highly heterogeneous in terms of study design, interventions, and outcome measures, ketogenic therapy appears promising in improving both acute and long-term cognition among patients with [Alzheimer’s and mild cognitive impairment],” the researchers summarized.