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Preventing Age-Related Cognitive Decline

April 2005

By Laurie Barclay, MD

Impairment of memory and learning need not accompany normal aging. Susceptibility to age-related cognitive decline varies widely among individuals, suggesting that interventions may be helpful in preventing its occurrence. A large body of scientific studies indicates that age-related cognitive decline may be partially controlled or prevented.

A particularly intriguing development in the field of brain health and longevity occurred with the release of a Canadian study on the use of a combination dietary supplement in the prevention of age-related cognitive decline.1 Using the transgenic mouse model of aging, researchers discovered that a cocktail of 31 nutrients and plant-based extracts abolished age-related cognitive decline in the test subjects. This exciting finding lends hope to the prospect of minimizing or eliminating cognitive decline in humans. In this article, we examine the mouse study and the nutritional and herbal remedies that make up this powerful anti-aging supplement.

Although findings from animal studies cannot be applied directly to humans, they shed light on mechanisms of brain aging and open fruitful avenues for human intervention. An interesting model for age-related cognitive decline is transgenic mice that are genetically modified to produce increased growth hormone, a crucial regulator of growth and aging.1

Young, mature transgenic mice learn mazes faster and with fewer errors than normal mice. As they age, transgenic mice accumulate more free radicals in the brain than normal mice, causing learning impairment and premature death.

In a recent study from McMaster University in Hamilton, Ontario, transgenic mice were fed a unique combination of nutrients designed to protect against age-related cognitive decline.1 This “anti-aging” supplement contained many vitamins, minerals, antioxidants, herbal extracts, and brain-supportive nutrients to improve the stability of nerve cell membranes, boost mitochondrial energy production, optimize insulin sensitivity, and reduce free-radical damage and inflammation.

After receiving this supplement daily for nearly three years, a large group of transgenic mice did not develop age-related cognitive decline. Older transgenic mice that were given the supplement learned a complex maze faster than younger, untreated transgenic mice, with virtually no impact on growth and no apparent negative consequences.1

With increasing age, untreated transgenic mice were dramatically worse—while treated transgenic mice grew progressively better—in terms of their number of errors and attempts required to learn the maze. Learning was at least 200–250% better in treated older transgenic mice than in untreated normal mice or in untreated older transgenic mice.1

Implications for Human Health

What are the implications of the transgenic mouse study for age-related cognitive decline in humans? If cognitive decline can be prevented in mice using a combination of supplements, then perhaps nutritional remedies can also prevent cognitive decline in humans. Recent findings from other studies suggests a sound rationale underlying each of the 31 nutrients composing the anti-aging supplement used in the mouse study.2,3 The anti-aging supplement included:

  • Energy enhancers (acetyl-L-carnitine, lipoic acid, coenzyme Q10)
  • Hormones (DHEA, melatonin)
  • B vitamins (B1, B3, B6, B12, folic acid)
  • Antioxidants (vitamin C, vitamin E, beta-carotene, green tea, L-glutathione, N-acetylcysteine)
  • Unsaturated fatty acids (cod liver oil, flaxseed oil)
  • Agents that support blood flow (ginkgo biloba, ginger, aspirin)
  • Minerals (chromium, magnesium, potassium, selenium, zinc)
  • Plant-based remedies (ginseng, bioflavonoids, garlic, rutin).

Many of these ingredients act in several different ways to protect against the ravages of aging, and are more effective when taken together than when taken individually.2,3

Animal studies, population studies in normal aging and in age-related diseases, and clinical trials all suggest that these nutrients are vital to brain health and might help protect against age-related cognitive decline.

Enhancing Brain Cell Energy

To perform its complex functions, the brain requires a continuous high-energy level. Aging brain cells are inefficient at glucose intake and mitochondrial energy production. This allows for the buildup of cellular debris, eventually destroying brain cells and causing age-related cognitive decline. Nutrients that can help restore energy production may therefore help prevent or control brain aging.

By transporting fatty acids into the mitochondria, the amino acid acetyl-L-carnitine helps to produce energy while preventing the accumulation of toxic fatty acids. Feeding acetyl-L-carnitine to aged rats for long periods reverses the buildup of toxic fatty acids in brain cell membranes to a more normal pattern typical of younger animals.4

Supplements combining acetyl-L-carnitine with the antioxidant lipoic acid help reverse mitochondrial breakdown, oxidative damage, and memory loss in old rats.2,3,5 Based on these promising results, this combination is being tested in humans.

“Each chemical solves a different problem—the two together are better than either one alone,” senior researcher Bruce Ames, a molecular biology professor at the University of California, Berkeley, said in a news release. “With the two supplements together, these old rats got up and did the Macarena. The brain looks better, they are full of energy—everything we looked at looks more like a young animal.”6

A recent review of well-controlled clinical studies suggests mild benefits of acetyl-L-carnitine in probable Alzheimer’s disease.7 Compared to placebo, acetyl-L-carnitine was better at improving memory scores.

“[Acetyl-L-carnitine] slows the progression of Alzheimer’s disease in younger subjects,” researchers concluded from a well-designed study of more than 300 patients, conducted at 24 US clinics.8

Another high-octane booster of brain energy is coenzyme Q10 (CoQ10), also called ubiquinone because it is present in every cell in the body. By facilitating synthesis of the basic energy molecule adenosine triphosphate (ATP), this potent antioxidant helps generate 95% of the body’s energy.

In animals, CoQ10 levels drop by about 25% with illness, 50% with aging, and 75% before death.9 Studies in old rats suggest that dietary CoQ10 reaches brain mitochondria, restores CoQ10 levels to those seen in young animals, and may protect against degenerative brain diseases.1

In a study of 80 patients with the degenerative neurological condition known as Parkinson’s disease, high dosages of CoQ10 slowed progressive worsening in function—especially feeding, dressing, bathing, and walking—by 44% compared to placebo.11 Based on these encouraging results, the researchers recommended additional testing in hundreds of patients.

Brain-Friendly Fatty Acids

Although the accumulation of toxic fatty acids can damage the brain, not all fatty acids are harmful. Brain cells use essential fatty acids, including EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), as fuel and as basic building blocks. Cod liver oil, cold-water fish, and flaxseed oil provide these omega-3 fatty acids.

By controlling chronic inflammation, omega-3 fatty acids may help reverse brain damage associated with aging and degenerative diseases. In studies with aged and young rats, DHA supplementation significantly decreased free-radical levels of lipid peroxide in the hippocampus, a brain region involved in memory, and also reduced errors in maze learning.12

Other benefits of omega-3 fatty acids include lowering blood triglycerides and preventing blood from clotting too quickly,13 which may indirectly improve brain function by increasing blood flow and reducing stroke risk.

In some individuals, depression contributes to memory decline with aging. Levels of omega-3 fatty acids in red blood cell membranes may be reduced in depressed people.14-16

In a study of 815 Chicago residents who were 65 years of age or older, the risk of developing Alzheimer’s disease over four years was 60% less for those who ate fish at least once a week than for those who rarely or never ate fish.17