AREDS, AREDS2 analyses show protection against cognitive decline, increased brain function

Adhering to a Mediterranean diet is associated with a lower risk of cognitive impairment and with higher cognitive function, but not with a slower decline in cognitive function, according to researchers for the Age-Related Eye Disease Study (AREDS) and AREDS2 Research Groups. A high intake of fish, however, was associated with a decreased risk of cognitive impairment and slower cognitive decline. Results are published in Alzheimer’s & Dementia.

“Diet may be an important factor in influencing progression to [mild cognitive impairment] MCI and dementia. As a modifiable environmental factor, diet can exert profound effects on biological aging, and has been associated with age-related conditions linked to dementia, including cardiovascular disease and diabetes. Regarding food groups, fish intake has attracted attention for an association with slower decline in cognition and memory. The Mediterranean diet pattern has received interest,” according to these researchers, led by Tiarnán D. Keenan, of the National Eye Institute, National Institutes of Health, Bethesda, MD.

A Mediterranean diet is strongly plant-based, and typically includes fruits, vegetables, bread and other grains, potatoes, beans, nuts and seeds, with olive oil as the primary fat source. Compared with the typical Western diet, the Mediterranean diet includes less dairy and meat, and focuses more on fish, shellfish, and some poultry.

The link between diet and cognition has been well-studied. However, among the 14 systematic reviews that have been conducted, results are inconsistent.

For their observational study, Keenan and colleagues conducted a post hoc analysis of data from 7,756 participants enrolled in two well-known, randomized trials of the efficacy of nutritional supplements on progression to late age-related macular degeneration (AMD)—AREDS and AREDS2. Both were phase III, multicenter, randomized clinical trials.

At randomization, all subjects filled out food frequency questionnaires (FFQs), which researchers used to determine the number of medium-sized servings of each food item subjects consumed per week. They also determined the intake for each of nine categories: whole fruits, vegetables, whole grains, nuts, legumes, red meat, fish, monounsaturated fatty acid:saturated fatty acid ratio, and alcohol. These were combined to calculate the modified Alternative Mediterranean Dietary Index (aMED) score.

Upon cross-sectional analysis, Keenan and fellow researchers found that higher aMED scores were associated with significantly lower risk of cognitive impairment and higher cognitive scores in both studies.

In AREDS, the odds ratios for cognitive impairment in aMED tertile 3 was 0.36 for Modified Mini-Mental State (˂ 80; P=0.001 compared with tertile 1) and 0.56 for composite score in AREDS (P=0.001). In AREDS2, these odds ratios were 0.56 for Telephone Interview Cognitive Status-Modified (˂ 30) and 0.48 for composite score (each P ˂ 0.0001).

Keenan et al. also found that fish intake was associated with higher cognitive function. Among participants in AREDS2, the rate of cognitive decline over 5 to 10 years was not significantly different according to aMED, but it was significantly slower in those with higher fish intake (P=0.019).

Unlike other studies, these researchers found no interactions between APOE or other genes associated with Alzheimer’s disease and either aMED or fish intake that influenced cognitive function.

Limitations of the study include its post hoc hypothesis generation, the exclusion of participants with substantial cognitive impairment, residual or unmeasured confounding, and differences between the cohorts studied. Assessment of participants’ diet via FFQ and differences in the AREDS and AREDS2 FFX may also have led to measurement errors.

Application of these results may have limited generalizability to populations with different diets and those without AMD.

“Higher aMED adherence was associated with lower risk of cognitive impairment and higher cognitive function scores, with dose-response relationships. This finding was consistent between the two study populations of older people without frank dementia at baseline, one comprising individuals with a wide spectrum of AMD severity (including no disease) and the other comprising individuals with at least intermediate AMD,” concluded Keenan and colleagues.

  1. Adherence to the Mediterranean diet was associated with a decreased risk of cognitive impairment and higher cognitive function.

  2. A higher intake of fish was also associated with a decreased risk of cognitive impairment, as well as slower cognitive decline.

E.C. Meszaros, Contributing Writer, BreakingMED™

Keenan reported no conflicts of interest.

This study was supported by AREDS and AREDS2, with funds from The Office of Dietary Supplements; the National Center for Complementary and Alternative Medicine; the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Cat ID: 33

Topic ID: 82,33,404,485,730,33,192,94,925,240


KeenanTD, et al “Adherence to a Mediterranean diet and cognitive function in the age-related eye disease studies 1 & 2” Alzheimer’s Dement 2020; 1–12. DOI: 10.1002/alz.12077.