Effects of long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation on cerebral circulation and cognitive function

Suitable participants will be required to attend the CNRC 5 times over the period of 20 weeks. Participants will arrive at the Clinical Nutrition Research Centre (CNRC) following an 8 h overnight fast for further screening to determine study eligibility. Anthropometric measurements of height, weight and waist circumference will be obtained before clinic blood pressure (BP) and arterial compliance (AC) measurements are assessed. Those with clinic BP not within the study inclusion range will be excluded. Participants will be fitted with a transcranial doppler (TCD) headpiece supporting an ultrasound probe on each temporal region. An investigator will adjust the probes until a measurable blood flow signal is obtained in each middle cerebral artery (MCA) and posterior cerebral artery (PCA). If the investigator is unable to obtain a blood flow signal in the PCA, the procedure for cerebrovascular responsiveness (CVR) to photic stimulation will not commence. However, if no measureable blood flow signal is detected in the MCA for the measure of CVR to hypercapnia, the participant will be excluded from the study. The dementia status of the participants will be determined using the Australian Version of the Modified Mini Mental State Examination (3MS). Participants scoring below 78/100 (considered an indicator of suspected dementia) will be excluded from this study. A blood sample analysis for the measure of Omega-3 index, pro-inflammatory biomarkers and blood lipids will be obtained from the participant. Due to the long fasting duration in the physiological assessment protocol (Part A), the psychological assessments (Part B) will be scheduled for the following day or within 7 days of completing the physiological assessments. This is to minimize the risk of hypoglycemia, which would affect the neuropsychometric test performance. Participants will return for neuropsychological testing following a 4 h fast (no food/beverage, except water). The TCD headpiece will be refitted on the participants and probes adjusted to obtain a measurable blood flow signal in each MCA. Continuous recordings of changes in mean blood flow velocities during the neuropsychological test battery will be obtained. At the conclusion of the test battery, participants will be asked to complete a scale to assess mood states. In addition, a short questionnaire of one’s dietary intake of long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) and the Self-reported Assessment of Subjective Cognitive Impairment (as previously captured in the Health, Diet & Lifestyle Questionnaire) will be administered at Visit 2 or 5 and for the purpose of determining test-retest reliability coefficients. Duration of the visit will last approximately 90 min. Light refreshments will be served at the conclusion of each visit. Participants will be randomly assigned to a treatment arm using allocation by minimization (Altman DG, Bland JM. Treatment allocation by minimisation. Brit Med J. 2005 Apr 9;330(7495):843-.). They will be required to consume 4 supplement capsules per day for 20 weeks, preferably at the same time each day. To assist with compliance, participants will note down the time of capsule consumption in their supplement diary. A study investigator will contact the participants every 4 weeks during the intervention to check participants’ well-being and to remind them to consume their supplements. Participants will return at week 10 to be reassessed for Part A of the protocol. To minimize learning effects, Part B will not be assessed at week 10. The purpose of this visit is to maintain participant-investigator contact and to assess treatment compliance, as assessed by erythrocyte LCn-3PUFA levels. Measuring cerebrovascular function mid-way in the intervention will provide insight into the trajectory of improvement. Participants will continue taking their allocated supplement from week 10 to 20 before returning for reassessment physiological and psychometric assessments.