Alzheimer’s disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester–based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.

Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mM and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD ؉ ]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.The metabolism of ketone bodies in the working perfused heart increased the supply of mitochondrial NADH and the ⌬G of ATP hydrolysis (1). Other than the observation that ketone bodies can replace glucose as the major energy substrate in brain (2), little is known about the precise effects of ketone metabolism in brain in vivo. The elevation of ketone bodies (3-hydroxybutyrate and acetoacetate) and free fatty acids through ketogenic diets have been used for almost a century to treat drug refractory epilepsy (3, 4). In addition, it has been suggested that mild ketosis might be an effective treatment for a number of neurodegenerative and other diseases (5-7). We therefore undertook a broad survey of the effects of a ketone ester-and a fat-supplemented diet on several of the pathways of intermediary and energy metabolism in rat brain.Prevention of postmortal changes, necessary for the accurate determination of in vivo redox and phosphorylation states in brain, require rapid inactivation of tissue, which was accomplished by freeze-blowing (8, 9 Elevation of blood ketone bodies, by either fasting or high fat diets, results in elevation of both blood ketone bodies and free fatty acids. Therefore, prior to this report, it has not been possible to investigate ketone body metabolism in brain independent of the effects induced by elevation of plasma free fatty acids.More recently, ketogenic diets have been used in the treatment of obesity where it has been shown that high protein, low carbohydrate diets decreased appetite, sensation of hunger, and food intake in hospitalized patients(10). The intraventricular infusion of 3-hydroxybutyrate (11, 12) or intravenous administration of its precursor 1,3-butanediol (13), have previously been shown to decrease food intake in the rat as has intraperitoneal injections of 3-hydroxybutyrate or 1,3-butanediol in the pigmy goat (14). Subcutaneo...

Objectives Nursing homes became epicenters of COVID-19 in the spring of 2020. Due to the substantial case fatality rates within congregate settings, federal agencies recommended restrictions to family visits. Six months into the COVID-19 pandemic, these largely remain in place. The objective of this study was to generate consensus guidance statements focusing on essential family caregivers and visitors. Design A modified two-step Delphi process was used to generate consensus statements. Setting and Participants The Delphi panel consisted of 21 US and Canadian post-acute and long-term care experts in clinical medicine, administration, and patient care advocacy. Methods State and federal reopening statements were collected in June 2020 and the panel voted on these using a three-point Likert scale with consensus defined as ≥80% of panel members voting “Agree.” The consensus statements then informed development of the visitor guidance statements. Results The Delphi process yielded 77 consensus statements. Regarding visitor guidance, the panel made five strong recommendations: 1) maintain strong infection prevention and control precautions, 2) facilitate indoor and outdoor visits, 3) allow limited physical contact with appropriate precautions, 4) assess individual residents' care preferences and level of risk tolerance, and 5) dedicate an essential caregiver and extend the definition of compassionate care visits to include care that promotes psychosocial wellbeing of residents. Conclusions and Implications The COVID-19 pandemic has seen substantial regulatory changes without strong consideration of the impact on residents. In the absence of timely and rigorous research, the involvement of clinicians and patient care advocates is important to help create the balance between individual resident preferences and the health of the collective. The results of this evidence-based Delphi process will help guide policy decisions as well as inform future research.