Vitamin E, DHA (docosahexaenoic acid, the omega-3 fat in fish), folate and saturated fat have all been shown to play a role in cognitive aging, explained Martha Clare Morris, Director of the Rush Institute for Health Aging and the MIND Centre, Chicago. Evidence demonstrating that carotenoids, flavonoids, trans fat, vitamin D, monounsaturated fat and polyphenols play a role is less strong.
Dietary interventions may therefore lower the risk of developing Alzheimer’s disease (AD), but randomized, controlled trials (RCTs) targeting nutritional factors are not only lacking but pose methodological challenges, said Professor Kivipelto. To date, there is no evidence that just one intervention is effective.
Given the multifactorial aetiology of AD, Professor Kivipelto added, it is probable that multidomain interventions may be the most effective strategy to prevent cognitive impairment and dementia. Multidomain interventions combine nonpharmacological and pharmacological approaches and target several risk factors and mechanisms simultaneously.
Targeting all stages of the AD pathogenetic process using a variety of approaches is the way forward
Important multidomain dietary and lifestyle RCTs discussed at the symposium were:
- FINGER (the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability)
- The European Union-funded LipiDiDiet project
- The National Institute on Aging-funded MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension diet] Intervention for Neurodegenerative Delay)-AD project
In 2015, FINGER provided the first evidence from a large RCT that a multidomain lifestyle intervention comprising nutritional guidance, physical exercise, cognitive training and social activities, might improve or maintain cognitive impairment in at-risk elderly people.1 The intervention was provided through individualized counselling and group-based activities.
The FINGER model is now being tested in diverse populations and settings
The FINGER model is now being tested in diverse populations and settings in the UK, US, China and Singapore; and many other countries are planning to become involved in the FINGER project, said Professor Kivipelto. The World Wide FINGERS Initiative2 is an interdisciplinary network to promote synergy across the trials and optimize efforts towards dementia prevention.
LipiDiDiet was the first completed RCT on nutrition in prodromal AD to show beneficial effects of a brain-targeted nutritional supplement on measures of disease progression after 24 months.3 This supports the role of nutritional intervention in prodromal AD, said Tobias Hartmann, Scientific Director of the German Institute for Dementia Prevention of the University of the Saarland, Germany.
Nutritional intervention has beneficial effects on prodromal AD
LipiDiDiet is a 6-year multi-country RCT including 311 patients with prodromal AD diagnosed using neuropsychological and AD biomarker assessment.
Participants were randomized to receive either an active food drink containing several nutrients to act on multiple biological pathways underlying AD; or control product once daily.
The study showed that the intervention had no significant effect on the neuropsychological battery primary endpoint over 2 years. However, this endpoint was inadequately powered because the cognitive decline in the control population was lower than expected.
The intervention did, however, have a beneficial effect on the secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy. The outcome was better for subjects who entered the trial with a higher baseline Mini–Mental State Examination score and better adherence to the intervention protocol.
The intervention was shown to have a benign safety profile and no serious adverse events were observed.
The ongoing multicentre Phase 3 MIND-AD project includes a hybrid Mediterranean-DASH diet that targets the brain, said Professor Morris. A notable difference from the Mediterranean and DASH diets is that the MIND-AD diet contains less vegetables and fruit, but stipulates one leafy green vegetable every day.
The study participants are 600 individuals without cognitive impairment aged between 65 and 84 years who are overweight and have suboptimal diets. The aim is to determine the effects of a 3-year dietary counselling intervention of the MIND diet together with 250 kcal/day caloric restriction on cognitive decline and brain macro- and microstructural integrity.
The primary outcome in MIND-AD is a decline in a global measure of cognition
The primary outcome is a decline in a global measure of cognition using a validated battery of 12 cognitive tests administered at five assessment periods over the 3-year period.
Secondary outcomes are measures of changes in brain macro- and microstructural integrity in a subset of 300 participants. Exploratory aims include cardiovascular-related outcomes and AD biomarkers.