Alzheimer s & Dementia · 2014 · 193 citations · 15 references
MedicineNeurologyPharmacologyDementiaGeriatric PharmacologyGeriatric PharmacotherapyAlzheimer DiseaseBrain Energy MetabolismCognitive ImpairmentDementia TreatmentKetone Body MetabolismNeurodegenerative DiseasesAlzheimer Disease DementiaCognitive PerformanceCognitive Performance ImpairmentKetonesMental State ExaminationPharmacological Treatment Of DementiaPredose Effectsβ-Hydroxybutyrate Metabolism
BACKGROUND: Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches. METHOD: Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12. RESULTS: The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels. CONCLUSION: KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet.
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Konrad Talbot, Hoau-Yan Wang, Hala Kazi et al. · Journal of Clinical Investigation · 2012 · 1.8K citations · Full text
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