Flaws in study design may limit detection of cognitive effects in diet trials

Overcoming past challenges may require integrating traditional population science tools with innovative biomarker measures in a precision medicine framework.

Study: Diets to promote healthy brain ageing. Image Credit: Tatjana Baibakova / Shutterstock.com

In a recent study published in Nature Reviews Neurology, researchers review the role of diet in preventing cognitive decline and dementia.

How does diet impact dementia risk?

Dementia is a major cause of mortality and morbidity throughout the world, with about 57.4 million individuals diagnosed with this disease in 2019. By 2050, researchers estimate that over 152 million people will be affected by dementia.

Despite these predictions, up to 40% of dementia cases could be prevented or delayed by managing modifiable risk factors like diet. Healthy diets can reduce the risk of numerous health conditions like type 2 diabetes and hypertension, both of which are also linked to dementia.

Although disease-modifying therapies for Alzheimer’s disease (AD) have the potential to improve patient outcomes, these treatments may put strain on healthcare systems and widen health disparities. Thus, it is crucial to develop effective prevention strategies at the individual and population levels.

Dietary patterns and cognitive health

Numerous observational studies have linked the Mediterranean diet, which is characterized by a high intake of fish, poultry, olive oil, and plant-based foods and low consumption of red meat and alcohol, to slower cognitive decline and a reduced risk of dementia.

Clinical trials have also reported cognitive benefits associated with the Mediterranean diet for individuals at high cardiovascular risk when supplemented with nuts or olive oil. Likewise, a meta-analysis found associations with better memory and global cognition; however, mixed results were observed for attention and executive function.

The Dietary Approaches to Stop Hypertension (DASH) diet, which focuses on the consumption of lean protein, nuts, whole grains, low-fat dairy, fruits, and vegetables while limiting alcohol, saturated fat, and red meat, has been associated with limited cognitive benefits in observational studies. In clinical trials, the DASH diet alone did not improve cognition; however, when combined with aerobic exercise, significant benefits were observed.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND diet) combines Mediterranean and DASH diets while emphasizing neuroprotective foods like green leafy vegetables, nuts, and berries and limiting unhealthy food products like red meat and fried foods.

Observational studies have produced mixed findings, with some reporting slower cognitive decline and others not observing any significant benefits associated with the MIND diet. Moreover, clinical trials have not reported significant cognitive improvements between MIND and comparison diets after three years.

Pro-inflammatory diets rich in fried foods and red meat increase the risk of adverse cognitive outcomes, whereas anti-inflammatory diets high in fruits and whole grains confer protective effects. Observational studies consistently associated pro-inflammatory diets with cognitive decline.

The plant-based diet has been shown to reduce the risk of dementia in vegetarians and slow cognitive decline in African Americans. Comparatively, the Nordic diet, which is high in berries, whole grains, fish, vegetables, and rapeseed oil consumption, was associated with less cognitive decline among older adults with high adherence.

Biological mechanisms

Healthy diets like the Mediterranean diet are associated with reduced amyloid-β and tau protein accumulation, both of which are biomarkers of AD, less brain atrophy, and slower hippocampal volume decline. Comparatively, high amounts of saturated fats and sugars increase the burden of AD biomarkers.

Healthy diets support cardiovascular health, which reduces dementia risk. Similarly, Mediterranean and DASH diets have been shown to reduce white matter lesions and brain infarcts, improve vascular function, and reduce endothelial dysfunction. However, there is mixed evidence on the long-term benefits of diets like the MIND diet.

Dysfunction in brain energy metabolism contributes to cognitive decline. In recent studies, the Mediterranean diet has been shown to support brain glucose metabolism, limit the decline in energy efficiency, reduce oxidative stress, and improve antioxidant markers. DASH and vegetarian diets also reduce lipid peroxidation and improve antioxidant defenses.

Chronic inflammation affects brain health and cognitive aging, which has been reduced after following the Mediterranean and DASH diets. The Mediterranean and MIND diets may also promote “epigenetic rejuvenation,” which slows biological aging. Gut microbiome health may also be involved in cognition; however, additional studies are needed to confirm this association.

Future outlook

Previous diet trials for dementia prevention have produced mixed results due to design limitations like participant selection, intervention intensity, and cognitive assessments. Thus, future studies that include high-risk groups, personalized diets, longer durations, and advanced biomarkers are needed. Moreover, the development of broader and scalable interventions and efforts to include underrepresented groups can enhance trial relevance and diversity.