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

• Published in: Neurobiology of aging Vol. 86; pp. 54 - 63
• Main Authors: Neth, Bryan J., Mintz, Akiva, Whitlow, Christopher, Jung, Youngkyoo, Solingapuram Sai, Kiran, Register, Thomas C., Kellar, Derek, Lockhart, Samuel N., Hoscheidt, Siobhan, Maldjian, Joseph, Heslegrave, Amanda J., Blennow, Kaj, Cunnane, Stephen C., Castellano, Christian-Alexandre, Zetterberg, Henrik, Craft, Suzanne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Alzheimer's disease; CSF biomarkers; Ketogenic diet; Mild cognitive impairment; MRI; Neurosciences; Neurovetenskaper; PET; CSF biomarkers; Mild cognitive impairment; MRI; Alzheimer's disease; Ketogenic diet; PET
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.09.015

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. •A modified ketogenic diet is well-tolerated with good compliance in older adults.•Participants had improved metabolic health after a modified ketogenic diet.•A modified ketogenic diet led to improved Alzheimer’s CSF biomarker profile.•Cerebral perfusion and ketone metabolism increased after a modified ketogenic diet.