Effect of Virgin Coconut Oil Supplementation on Cognition of Individuals with Mild-to-Moderate Alzheimer's Disease in Sri Lanka (VCO-AD Study): A Randomized Placebo-Controlled Trial.

BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer's disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥Results:There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥Conclusion:Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.

Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis.

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.

Effects of Testosterone Supplementation on Separate Cognitive Domains in Cognitively Healthy Older Men: A Meta-analysis of Current Randomized Clinical Trials.

BACKGROUND: An increasing body of literature suggests a positive, neuroprotective effect for testosterone on cognition in older men. However, randomized clinical trials (RCTs) examining the effects of testosterone supplementation (TS) on cognitive function have been inconclusive. OBJECTIVE: To investigate the potential for TS to prevent cognitive decline in otherwise cognitively healthy older men, by examining the differential effects of TS on cognitively healthy older men in RCTs. METHODS: Comprehensive search of electronic databases, conference proceedings, and grey literature from 1990 to 2018 was performed to identify RCTs examining the effects of TS on cognition before and after supplementation, in cognitively healthy individuals. RESULTS: A final sample of 14 eligible RCTs met inclusion criteria. Using pooled random effects expressed as Hedge's g, comparison of placebo versus treatment groups pre- and postsupplementation showed improvements in the treatment group in executive function (g (11) = 0.14, 95% confidence interval [CI]: 0.03-0.26, z = 0.56, p = 0.011). However, it was noted that two studies in our sample did not report a significant increase in mean serum total testosterone (TT) levels in the treatment group after supplementation. Following exclusion of these studies, analysis indicated improvement in the treatment group for the overall cognitive composite (g (11) = 0.18, 95% CI: 0.02-0.33, z = 2.18), psychomotor speed (g (3) = 0.22, 95% CI: 0.01-0.43, z = 2.07) and executive function (g (9) = 0.15, 95% CI: 0.03-0.28, z = 2.35). No significant differences were noted for the global cognition, attention, verbal memory, visuospatial ability or visuospatial memory domains. CONCLUSION: Overall, our findings support the potential for TS as a preventative measure against cognitive decline, although the effect sizes were small. These findings warrant further observational studies and clinical trials of good methodological quality, to elucidate the effect of TS on cognition.

Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease.

For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid ß aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults.

Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n 96) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; time×treatment; F=3·85, P<0·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration.

Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific brain regions that occur in preclinical AD.

The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men.

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer's disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 weeks washout, and then 24 weeks of placebo (P); the second group (Group B) received the same treatments, in reverse order (Placebo, washout, and then T treatment). In group A (TèP), compared to baseline, there was a modest (1 point) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination (MMSE) following testosterone treatment. This improvement from baseline was sustained following the washout period and crossover to placebo treatment. Similar Mini Mental State Examination (MMSE) scores were observed when comparing testosterone treatment with placebo. In group B (PèT) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment. Improvements in baseline depression scores (assessed by Geriatric Depression Scale) were observed following testosterone/placebo treatment in both groups, and no difference was observed when comparing testosterone with placebo treatment. Our findings indicate a modest improvement on global cognition with testosterone treatment. Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment.