Context In preclinical Alzheimer’s disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. Objective This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. Data Sources A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. Data Extraction Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. Data Analysis All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. Conclusion MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. Systematic Review Registration PROSPERO registration number CRD42019146967.
Background:The increase in the ageing population is accompanied by increased rates of cognitive decline and dementia, which has a profound impact on both morbidity and mortality and a significant care-related stress and financial burden. In the new global economy, dementia has become a central issue for public health in Australia. Dementia is the second greatest cause of death in Australia and about 60% of all dementia cases are due to Alzheimer's disease (AD). In AD, damage starts occurring in the brain 20 to 30 years prior to any cognitive symptom. There is currently no cure for AD. However, the year between the start of its development and the appearance of symptoms represent a window of opportunity for implementing strategies to delay or prevent the progression of the disease through lifestyle interventions.Method: The study will be conduct in two parts: 1) A systematic review based on multidomain interventions. 2) AU ARROW Intervention.A comprehensive search of electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) will be performed to retrieve publications and alerts were set to identify publications until 31 august 2021.Results: An expected positive outcome would give more evidence that lifestyle changes and if a single nutrient itself or a whole pattern as MIND DIET that are relatively easy to adopt, can help to prevent or delay brain function decline and dementia, such as Alzheimer's disease dementia in an Australian population Conclusion: a multidomain intervention focused on cognitive training, and nutritional and physical activity counselling seems decrease cognitive decline in older adults.
BackgroundAlzheimer’s disease (AD) neuropathology begins 20 to 30 years before clinical diagnosis. Thus, there is an opportunity to implement strategies to prevent the progression of AD. Insulin resistance in the brain causes a disruption in glucose utilisation. Medium‐chain fatty acids (MCFA) are readily available substrates for the synthesis of ketone bodies (KB), which are an alternative brain fuel not controlled by insulin. A constant supply of KB may close the energy gap in the AD‐prone brain, and in doing so prevent or delay symptom onset, or protect the brain from further degeneration. There is increasing evidence that multidomain lifestyle interventions with dietary components significantly impact cognitive decline. Yet, these interventions have not considered the effects MCFA supplementation, to ensure sufficient energy for the brain.MethodThis is a phase II placebo‐controlled, randomised double‐blind 24‐month intervention trial of MCFA supplementation within the AUstralian‐multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention (AU‐ARROW) study, to investigate the additive effect of MCFA supplementation in older adults at increased risk of AD. A total of 124 participants will be recruited aged 60‐79 years, with subjective cognitive decline. Participants will be randomised 1:1 into either the intervention or placebo groups and will consume 3 daily doses at 15mL per dose of either MCFA or placebo supplement whilst continuing the AU‐ARROW protocol, which includes dietary education, physical activity, brain training, and health education.ResultThe primary outcomes involve statistical assessment of cognition, blood ketone body levels, and brain glucose utilisation. At baseline, and every 6 months, participants will have fasting blood samples collected. At baseline, 12, and 24 months, participants will undergo cognitive assessments. At baseline and 24 months, participants will undergo fluorodeoxyglucose positron emission tomography scans to determine brain glucose utilisation.ConclusionThe final protocol is expected to maximise data collection and analyses. Combined with AU‐ARROW, it will allow for a) the implementation of MCFA supplementation guidelines in a plan to reduce cognitive decline and risk of AD, b) the determination of effects of MCFA consumption on neuroimaging and blood‐based biomarkers, and c) the comparison of between subject differences.
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