Higher blood carotenoid levels are linked to slower cognitive decline in older adults carrying the APOE ε4 Alzheimer risk allele. Digest
Carriers of the apolipoprotein E (APOE) ε4 gene variant face a higher risk of Alzheimer's disease, yet practical ways to reduce that inherited vulnerability are limited. Researchers of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial analyzed whether carotenoids, natural pigments abundant in fruits and vegetables such as carrots, sweet potatoes, and spinach, might be one such lever.
They focused on a group of 442 adults aged 65 and older who were overweight or obese, had a family history of Alzheimer's disease, followed diets that didn't meet the trial's healthy eating guidelines, and had no major cognitive impairment at the start of the study. All contributed APOE genotyping data and were followed with repeated cognitive testing over three years. When the study began, researchers evaluated total plasma carotenoid levels and five carotenoid markers: alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene.
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Cognitive trajectories diverged markedly with higher carotenoid levels in APOE ε4 carriers:
- For people carrying the APOE ε4 variant, higher total carotenoid levels were modestly but meaningfully linked to better cognitive performance after three years. These associations held up across all six carotenoids.
- Comparing APOE ε4 carriers with high and low total carotenoid levels, the difference in cognitive decline was roughly equivalent to being three years younger.
- For lycopene and beta-cryptoxanthin, both medium and high carotenoid levels were linked to even larger benefits, equivalent to being about 4 to 6 years younger.
- APOE ε4 carriers and noncarriers with high carotenoid levels followed similar cognitive paths, while carriers with low carotenoid levels had the fastest decline.
- Among people without the APOE ε4 gene variant, carotenoid levels were not meaningfully related to changes in cognition.
Carotenoids do not just circulate in the bloodstream, they also make their way into the brain. Several of them, especially lutein and zeaxanthin, are known to accumulate in brain regions involved in memory, learning, and executive function (the systems that manage goals and task switching). Their presence is important because they can help neutralize oxidative stress, temper inflammation, and stabilize cell membranes, which are stress points in aging brains. APOE ε4 heightens brain oxidative stress and inflammation and weakens antioxidant defenses. So, higher circulating carotenoid levels may help buffer ε4 carriers against this vulnerability.
Although the MIND diet included carotenoid-rich foods, the study was not specifically designed to test their effects. The findings are observational and do not establish cause and effect. Still, the pattern suggests that nutrient status may interact with genetic risk to shape brain aging. In Q&A #55, I discuss the effects of astaxanthin, lutein, and zeaxanthin on cardiovascular and brain health in more detail.