The effects of docosahexaenoic acid combined with supporting nutrients and physical activity on mobility and cognitive function in older women.

Abstract

There is a complex interplay between mobility and cognition in older adults. It has previously been shown that a high DHA multi-nutrient supplement improves habitual walking speed, verbal memory, and psychomotor response latency in older women. Exercise also improves mobility and cognition in older adults, and omega-3 fatty acids and exercise share a range of overlapping biological effects. The primary aim of this thesis was to conduct a randomised semi-blinded placebo controlled study exploring the effects of a high DHA multi-nutrient supplement and aerobic exercise, alone and in combination, on mobility and cognition in older women. One the novel aspects of the research conducted within the thesis is the use of a multi-nutrient-intervention which includes both omega-3 polyunsaturated fatty acids (PUFA) and B vitamins. There is now evidence to suggest that there may be an interaction between B vitamins and omega-3 polyunsaturated fatty acids, with suggestions that optimising intake of both nutrients being key to eliciting benefits to cognition within older adults. As such, a systematic review was conducted to investigate whether supplementation with a combination of omega-3 PUFAs and B vitamins can prevent cognitive decline in older adults. Randomised control trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of omega-3 PUFAs and B vitamins alone, or in combination with other nutrients and trials which tested for interactions between omega-3 PUFAs and B vitamins by providing omega-3 PUFA alone and also measuring B vitamin status or provided B vitamin supplementation alone and measured omega-3 PUFA status. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus, and MEDLINE. A total of 14 papers were included in the analysis (n=4913; age: 60-70 y; follow up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both omega-3 PUFAs and B vitamins, versus placebo on global cognition assessed using composite scores from a neuropsychological test battery (G=0.23, p=0.002), global cognition using single measures of cognition (G=0.28, p=0.004) and episodic memory (G=0.32, p=0.001). The results indicate that providing a combination of omega-3 PUFA and B vitamins benefits cognition in older adults versus a placebo, the potential for an interaction between these key nutrients should be considered in future experimental work. The first aim of the program of experimental work was to assess feasibility and establish appropriate methods for testing of cognitive function and mobility. These aims were addressed through a series of pilot and feasibility studies. Five young healthy adults (mean age 29 y, SD 3) and four healthy older adults (mean age 70 y SD 8) were taken through a testing battery which consisted of tests of both gait and cognitive function. Gait testing was performed using opal inertial sensors and was conducted under single and dual task conditions. Two different dual-task scenarios were used, a 3-back and 7-back condition. Cognitive testing consisted of assessment of verbal memory, spatial working memory, executive function and interference control. There was evidence for floor effects of the 7-back dual task scenario as such only the 3-back condition was taken forward into the subsequent clinical trial. There was no evidence of floor or ceiling effects in the cognitive testing and thus no adjustments were made to the difficulty of these tasks. In conclusion this pilot/feasibility study allowed the researcher to familairise themselves with the testing protocols, established timings and protocols for clinical visits and allowed for the selection of mobility and cognitive testing that were at an appropriate level of difficulty for the target population. The second phases for the research process was to conduct a pilot study to establish a reliable method for assessing whole blood fatty acids on the research site. Five blood samples were taken from the fingertip of a volunteer from a single puncture using an automated lancet. Blood spots were collected on filter paper which had been pre-treated with 2,6-di-tert-butyl-p-cresol (butylated hydroxytoluene, BHT) diluted in ethanol at 2 mg/ml. Fatty acid methyl esters (FAME) were extracted from these blood samples. FAMES were quantified using a gas chromatograph with flame ionisation detector (GC-FID). The coefficient of variation for each fatty acid was calculated. To be deemed reliable a coefficient of variation of <10% for the main fatty acids of interest, EPA, DHA and AA and <15% for all other measured fatty acids would need to be achieved. The coefficient of variance for EPA, DHA and AA was 5.1%, 7.2% and 9.63% respectively, all other fatty acids were <15%. In conclusion, this method was successfully established and a standard operating procedure was produced for the research site. Results indicate that the method used, storage conditions, sample handling and user proficiency are reliable and can produce consistent results. To address the primary aim of thesis a randomised semi-blinded placebo controlled study was conducted Women (mean age 67 y, SD 8) were assigned to the following groups: multi-nutrient (1 g DHA, 160 mg EPA, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20 mg d- tocopherol, 1 mg folic acid, and 20 µg vitamin B12 per day, N=13), multi-nutrient and exercise (spin class twice per week, N=14), exercise and placebo (N=12), or placebo (N=12). The multi-nutrient was given for 24 weeks, and exercise for 12 weeks. Trial registration: NCT03228550. Baseline correlational analysis performed on mobility outcomes revealed a significant positive relationship between whole blood DHA and dual-task gait speed (R=0.318 p=0.018) and dual task effect on gait speed (R=0.312 p=0.019). No other relationships were identified for EPA, DHA:AA or serum homocysteine with any other mobility outcome. Following the post intervention period no treatment effects were observed for the primary outcome, habitual walking speed. Improvements in verbal memory and executive function were seen for all treatments groups versus placebo (all, p<0.05). Significant improvements in self-reported emotional wellbeing were seen with multi-nutrient and exercise groups versus placebo (p=0.03). Per-protocol analysis revealed benefits of aerobic exercise on habitual and fast walking gait speed and the combined multi-nutrient supplement and aerobic exercise lead to improved time on the five times sit to stand test (all, p<0.05). The results suggest that a high DHA multi-nutrient supplement and aerobic exercise produce similar improvements in cognitive function to aerobic exercise in healthy older adults. It was not possible to establish whether combining the interventions lead to additive or synergistic benefits. Combining the multi-nutrient supplement with aerobic exercise did elicit positive effects on emotional wellbeing and ability to rise from a chair, which were not observed for each intervention separately, offering the intriguing prospect that the combination of a high DHA multi-nutrient supplement and exercise may have a broader impact across multiple healthy ageing outcomes.