Memory Intervention with Nutrition for Dementia (re-MIND)

Inclusion criteria: 1. Diagnosis of mild to moderate Alzheimer's disease 2. Aged >65 years Exclusion criteria: 1. Consumption of carotenoids and/or omega supplements within the last 3 months 2. Inability to swallow capsules 3. Depression (under active review and medication change) 4. Previously confirmed stroke disease and/or infarct on brain scan 5. Mini‐Mental State Evaluation (MMSE) >24 6. Intact clock drawing test and semantic fluency test (i.e. naming more than 11 objects starting with the letter F in 1 minute) Alzheimer's disease Nervous System Diseases Alzheimer's disease Block randomisation will be performed using a trial management system “Trial Controller” designed by our research group. 120 patients will be randomised in a 2:1 (Active:Placebo) masked fashion. 80 AD subjects will consume 3 active capsules a day, combined the soft gels contain: 10 mg L, 10 mg MZ, 2 mg Z, 1 g fish oil and 15 mg alpha‐tocopherol. 40 AD subjects will consume 3 placebo capsules (sunflower oil) a day. Subjects will consume the intervention every day (3 soft gels with a meal) and will be followed for 24 months. Study visits are at baseline, month 12 and month 24 (final visit). AD progression assessed using using mini mental state examination (MMSE) at baseline (visit 1), 12 months (visit 2) and 24 months (final visit). MMSE is a 30‐point questionnaire that can be used to systematically and thoroughly assess mental status. It is an 11‐question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Mild to moderate AD is defined as score of 10 to 25. 1.Quality of life, assessed using using Quality of life in Alzheimer's Disease family and Participant version (QOL‐AD). QOL‐AD is a 13‐item scale (total score range 13–52; higher scores indicate better QOL). The QOL‐AD scale uses a scale of 1–4 (poor, fair, good, or excellent) to rate a variety of life domains, including the patient’s physical health, mood, relationships, activities, and ability to complete tasks. The researcher will interview the patient and patient’s carer separately. 2. Functional ability assessed using Dementia Severity Rating Scale (DSRS) and Clinical frailty score. 2.1. The DSRS is an informant‐based, multiple‐choice questionnaire that assesses severity from the mildest to the most severe stages in the major functional and cognitive domains affected in AD. Sections include: memory, speech and language, recognition of family members, orientation to time, orientation to place, ability to make decisions, social and community activity, home activities and responsibilities, personal care/cleanliness, eating, control of urination and bowels, and ability to get from place to place. Results are interpreted by adding up the points for all sections. Score of 0‐18: mild, score of 19‐36: moderate, and score of 37‐54: severe. 2.2. Clinical frailty score (0‐9) is recorded by the research nurse using a visual analogue scale. It is expected that mild to moderate AD patients will have a high score (i.e. 7). Functional ability will be evaluated by assessing the scores of each test over time (i.e. improvements, no changes and/or decline over 24 months). 3. Clinical collateral: a descriptive “story” of each subject will be recorded by the researcher including an interview of the patient’s carer (the primary person responsible for caring for the patient with Alzheimer's disease) to assess the patient’s health status and medical observations. Structured questions include: 3.1. Have you noticed any change in the patient's memory (same, worse, better)? 3.2. What are the main memory concerns? 3.3. How are they managing every activities – specifically getting dressed, making a cup of tea, cooking, grocery shopping? 3.4. Has there been a change in personality – specifically agitation, wandering, low mood, sleep disturbance? 4. Near acuity and contrast sensitivity measured using the M&S Technologies system. The test is carried out in the patient's home and controlled by the researcher using a smart system tablet (Android). The research nurse can customize the layout (e.g. distance and symbols) to each patient’s preference. 5. Dietary intake of lutein (L), zeaxanthin (Z), and omega. L and Z levels in the diet are assessed by inputting the patient’s weekly intake of carotenoid‐rich foods (eggs, broccoli, corn, dark leafy vegetables) into the 'L/Z screener' to give a carotenoid‐based diet score. Values are weighted for frequency of intake of the food and for bioavailability of L and Z within these foods. A ranking score re?ecting the relative intakes (representing arbitrary units) will be generated and used in analysis. Similarly, a subject’s weekly intake of fish (e.g. herring, sardines, salmon) and seeds (linseed oil and flaxseeds) will be inputted into the 'Omega screener' to give a gram per day omega consumption. AD subject’s dietary habits will be con?rmed by a family member or carer. 6. Measurement of serum concentrations of L, Z, meso‐zeaxanthin (MZ), and vitamin E assessed using non‐fasting blood samples. 7. Skin carotenoid concentration scores assessed using the Pharmanex® BioPhotonic S3 Scanner. This scanner measures carotenoid levels in human tissue at the skin surface (palm of the hand) using optical signals (resonant Raman spectroscopy). These signals identify the unique molecular structure of carotenoids, allowing their measurement without interference by other molecular substances. The individual is asked to place a specific point (between the maximal and distal palmar creases, directly below the fifth finger) of their right hand in front of the scanner’s low‐energy blue light for 30 seconds. From this, a skin carotenoid score (SCS) will be generated, which provided an indication of the individual’s overall antioxidant levels. This was repeated twice more and an average score was calculated. This technology is safe and has been previously validated against serum carotenoid concentrations. 8. Gas chromatography analysis of DHA and EPA assessed using non‐fasting blood samples. All secondary outcome measures will be measured at baseline (visit 1), 12 months (visit 2) and 24 months (final visit).