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Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study.

Journal article
Authors Bryan J Neth
Akiva Mintz
Christopher Whitlow
Youngkyoo Jung
Kiran Solingapuram Sai
Thomas C Register
Derek Kellar
Samuel N Lockhart
Siobhan Hoscheidt
Joseph Maldjian
Amanda J Heslegrave
Kaj Blennow
Stephen C Cunnane
Christian-Alexandre Castellano
Henrik Zetterberg
Suzanne Craft
Published in Neurobiology of aging
Volume 86
Pages 54-63
ISSN 1558-1497
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 54-63
Language en
Subject categories Neurochemistry


There is currently no established therapy to treat or prevent Alzheimer's disease. The ketogenic diet supplies an alternative cerebral metabolic fuel, with potential neuroprotective effects. Our goal was to compare the effects of a modified Mediterranean-ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) on cerebrospinal fluid Alzheimer's biomarkers, neuroimaging measures, peripheral metabolism, and cognition in older adults at risk for Alzheimer's. Twenty participants with subjective memory complaints (n = 11) or mild cognitive impairment (n = 9) completed both diets, with 3 participants discontinuing early. Mean compliance rates were 90% for MMKD and 95% for AHAD. All participants had improved metabolic indices following MMKD. MMKD was associated with increased cerebrospinal fluid Aβ42 and decreased tau. There was increased cerebral perfusion and increased cerebral ketone body uptake (11C-acetoacetate PET, in subsample) following MMKD. Memory performance improved after both diets, which may be due to practice effects. Our results suggest that a ketogenic intervention targeted toward adults at risk for Alzheimer's may prove beneficial in the prevention of cognitive decline.

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