Both offensive and defensive strategies are needed to prevent cognitive aging.

By Hara Estroff Marano

If you want to keep your brain young—and who doesn’t—your best bet is to inhabit, or design, or tie yourself to a cognitively stimulating environment, one filled with physical activities, social interaction, challenging work, spirited conversation, crossword puzzles, a new language, or a musical instrument to master. A cognitively demanding occupation will do, too. Cognitive effort, especially when begun young, is the most effective inducer of cognitive resilience; it can even keep some people functioning well despite neurodegenerative disease.

Scientists now know why. All across the life span, enriched environments stimulate neuronal activity, and the activity turns on a family of transcription factors—monocyte enhancer factor 2, or MEF2—known to be important in neural development. In fact, MEF2 plays a role in the development and proliferation of many kinds of tissue, including the heart and other muscles.

In the brain, MEF2 maintains neural transmission and encourages synaptic density. Synaptic plasticity, the ability of neurons to grow new connections and reorganize their circuitry, is altered in the aging brain and is a fundamental mechanism of age-related cognitive decline. Environmental enrichment upregulates the production of MEF2—enough so that, even in those with the pathological hallmarks of dementia, researchers find, it can sometimes rescue brain cells from the disruption brought about by the accumulation of toxic proteins. Its action seems to be specific to those neurons made pathologically hyperexcitable by such proteins.

In animal studies, stimulating superexpression of MEF2 maintains cognitive flexibility. It has “profound effects” on the ability to quickly and effectively integrate new information into existing schemas. Boosting MEF2 is being eyed by scientists as a potential drug target for minimizing the effects of neurodegenerative diseases such as Alzheimer’s.

Actively promoting continual brain development is one—and a very important—approach to keeping the brain young. It is, in fact, the only known preventive approach. But just as both offensive and defensive strategies are a necessary combination on the sports field, so are both important in the brain. It is at least as vital to protect the brain cells that already exist. One of the most important ways is to combat so-called oxidative stress.

The brain is especially vulnerable to constant wear-and-tear because it is an extremely metabolically busy organ, consuming a disproportionate share of oxygen in order to power all our thoughts and feelings, not to mention all the directives to other body parts to carry out our plans. The problem is that, after doing its part to create energy in the mitochondria of cells, oxygen leaks out as free radicals, a form that is highly unstable, readily reacts with other components of cells, including DNA, and damages the cellular machinery.

Free radicals of oxygen are especially likely to attack the lipids that stabilize nerve cell membranes, impairing cellular activity and cell signaling. Over time, the cumulative damage from oxidative stress shows up as memory problems, slowing and disorganization of functions, even depression.

The brain has its own antioxidant defense system, but its high energy requirements and abundance of lipids make it an easy target for oxygen assault. Under normal conditions, a constant supply of agents is needed to nullify oxidizing free radicals, prompt the removal of damaged biomolecules before they impair cellular operations, and maintain good brain function. Many foods—and especially fruits and vegetables—contain substances that act as antioxidants, fortifying the brain’s own antioxidant defense systems or directly scavenging the highly reactive, rogue oxygen molecules to mitigate the toxicity they wreak.

Some of the most notable are selenium, coenzyme Q, and vitamins C and E. Plants are naturally rich in the powerful antioxidants chemically classed as polyphenols. There are more than 8,000 of them bearing such names as flavonoids, tannins, lignans, and more. Many antioxidants are substances produced by plants as a form of protection against environmental assaults—by drought, by overexposure to sunlight, by bugs.

That peppery pinch in the back of the throat that is the hallmark of high-quality extra virgin olive oil? It’s due to the presence of the antioxidant (and anti-inflammatory) polyphenol oleocanthal, thought to be responsible for many of the health benefits of the Mediterranean diet. Rich as olive oil is in oleocanthal, there’s none in olives themselves. The antioxidant compound is created through the pressing process that releases the oil.

While the need for antioxidants can often be met through a nutrient-rich diet, studies suggest that an array of situations—whether strokes, exposure to environmental pollution, the use of various medications, or being at risk for macular degeneration—up the need for antioxidants. Cardiologists often prescribe antioxidant supplements to those taking statin medications, which lower lipid levels but also deplete the antioxidant coenzyme Q. Clinical studies of high-dose antioxidant supplementation for general disease prevention have often met with mixed results; nevertheless, significant research is focused on developing specific combinations of antioxidants as supplements to guard against brain aging and other conditions.

Welcome as your morning cup of coffee may be to jump-start your day, it is also an ally against brain aging. It doesn’t just improve alertness and reaction time; among its hundreds of bioactive compounds besides caffeine are, yes, polyphenols such as chlorogenic acid and lignans, known to reduce oxidative stress. Caffeine itself has been shown to improve long-term memory and reduce lipid peroxidation in the brains of the elderly. Studies show it also boosts the brain’s own antioxidant defense system.

Vitamin C, also called ascorbate or ascorbic acid, is a cofactor for a number of enzymes and can not only scavenge free radicals but inhibit the generation of them altogether. The highest concentrations of ascorbate in the body are found in the brain and neuroendocrine tissues such as the adrenal gland. Ascorbate deficiency is thought to particularly sensitize neurons to oxidative stress. Literature reviews and clinical studies link vitamin C deficiency with both an increase in depression and development of cognitive impairment.

Vitamin E, a nutrient that exists in eight forms differently distributed in foods, is considered one of the most important antioxidants in the brain: It blocks the oxidation of lipids, thus protecting cell membranes. All eight forms of the vitamin are free-radical scavengers. Multiple studies have shown that blood levels of the vitamin are lower in Alzheimer’s patients than in control subjects. That would seem to make vitamin E supplementation a perfect treatment for curbing aging of the brain.

But more than two decades of clinical studies of vitamin E supplementation in Alzheimer’s patients have yielded mixed results. It may be because only a single form of the vitamin was tested or that natural variations in patient responsiveness were not accounted for. There’s some evidence that vitamin E complex may be more effective in maintaining cognitive capacity rather than in treating cognitive decline.

And there’s even more evidence that it works best in combination with other antioxidant nutrients, such as vitamin C. Isn’t that what your mother said? Eat your veggies…all of them.

Fast Facts

Human life span has increased by nearly a decade in the United States in the past 50 years.

• Dementia cases are forecast to triple worldwide by 2050.
• A decrease in the prevalence of dementia due to education is offset by an increase due to heart health risk factors.
• In animal studies, environmental enrichment not only enhances cognitive function, it reduces symptoms of anxiety and depression after exposure to chronic stress
• Despite composing only 2 to 3 percent of total body weight, the brain uses about 20 to 25 percent of the body’s oxygen supply and is the prime generator of highly reactive oxygen molecules.
• Highly reactive oxygen species are produced in the brain’s mitochondria as they generate adenosine triphosphate (ATP) to power all the electrophysiological activity of nerve cells.
• According to the National Institutes of Health, supplements collectively account for 54 percent of all vitamin C intake and 64 percent of vitamin E consumption.
• Oleocanthal, the phenolic antioxidant in extra virgin olive oil, inhibits the toxic tangling of tau protein that is a marker of Alzheimier’s disease pathology. It also acts to clear aberrant amyloid protein.
• Human beings share with guinea pigs, some bats, and certain other primates the distinction of being among the few animals that cannot synthesize vitamin C.

Originally published at Psychology Today