Nare Torosyan1, Chakmeedaj Sethanandha2, Joshua D Grill3, Michelle L Dilley4, Jooyeon Lee4, Jeffrey L Cummings5, Celine Ossinalde4, Daniel H Silverman6. 1. Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA; Institute for Memory Impairments and Neurological Disorders, Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, University of California, Irvine, 3206 Biological Sciences III, Irvine, CA 92697, USA. 2. Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA; Mahidol University, 999 Phutthamonthon Sai 4 Rd, Chang Wat Nakhon Pathom 73170, Thailand. 3. Institute for Memory Impairments and Neurological Disorders, Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, University of California, Irvine, 3206 Biological Sciences III, Irvine, CA 92697, USA. 4. Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA. 5. Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W Bonneville Ave, Las Vegas, NV 89106, USA. 6. Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA. Electronic address: dsilver@ucla.edu.
Abstract
BACKGROUND:Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD. METHODS:Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were givenplacebo. Subjects received 4 15O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis. RESULTS: Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF. CONCLUSION: Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele.
RCT Entities:
BACKGROUND:Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD. METHODS: Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were given placebo. Subjects received 4 15O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis. RESULTS: Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF. CONCLUSION: Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele.
Authors: Antoine Hone-Blanchet; Botond Antal; Liam McMahon; Andrew Lithen; Nathan A Smith; Steven Stufflebeam; Yi-Fen Yen; Alexander Lin; Bruce G Jenkins; Lilianne R Mujica-Parodi; Eva-Maria Ratai Journal: Neuropsychopharmacology Date: 2022-08-22 Impact factor: 8.294
Authors: Eric D Vidoni; In-Young Choi; Phil Lee; Gregory Reed; Na Zhang; Joseph Pleen; Jonathan D Mahnken; Jonathan Clutton; Annette Becker; Erica Sherry; Rebecca Bothwell; Heidi Anderson; Robert A Harris; William Brooks; Heather M Wilkins; Lisa Mosconi; Jeffrey M Burns; Russell H Swerdlow Journal: Alzheimers Dement Date: 2020-07-27 Impact factor: 21.566