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[F3–04–02]: THE KU ALZHEIMER'S DISEASE KETOGENIC DIET FEASIBILITY AND RETENTION TRIAL: RESULTS FROM A PILOT STUDY
Author(s) -
Swerdlow Russell H.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.275
Subject(s) - ketogenic diet , ketosis , medicine , clinical dementia rating , dementia , clinical trial , adverse effect , medium chain triglyceride , regimen , physical therapy , disease , pediatrics , triglyceride , endocrinology , psychiatry , epilepsy , cholesterol , diabetes mellitus
mitochondrial respiration, increased mitochondrial hydrogen peroxide production and induction of the cytosolic-phospholipase-A2 sphingomyelinase pathway. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its sequentially phased activation, links glucose hypometabolism and mitochondrial dysfunction associated with endocrine aging with later age development of white matter degeneration. Conclusions: The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. The mechanistic pathway leading to white matter catabolism in the aging female brain provides multiple therapeutic targets to prevent and treat white matter degeneration in AD. Further, the pathways leading to catabolism of white matter in the female brain is likely to be relevant to the aging male brain at risk for AD. Therapeutically targeting stages of disease and associated mechanisms will be critical. Research was supported by NIH National Institute on Aging P01AG026572 and R01AG032236 to RDB.