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Preserving Cognitive Function with Aging

March 2009

By Julius Goepp, MD

UMP’s Role in Cognition Enhancement

UMP’s Role in Cognition Enhancement

Another approach to cognition and memory enhancement is the use of a substance known as uridine-5’-monophosphate (UMP), which helps comprise RNA, the DNA-like structure that cells use to create proteins from blueprints in genes. UMP supplementation in animals dramatically increases the production of vital brain cell membrane structural molecules, such as CDP-choline.61 Such structural molecules are vital for cell growth and repair, and even more importantly, for proper function of the synapses, the relay points at which brain and nerve cells communicate with each other.62

UMP supplementation in animals not only increases the synthesis of those vital proteins and phospholipids, but it actually helps stimulate production of neurotransmitters and of the tiny but critical cell outgrowths called neurites63 that are themselves formed and then remodeled in the process of learning64-66 and of cell repair.67

Brain scientists at MIT took those observations to a higher level when they supplemented nutritionally impoverished rats with UMP and studied the effects on memory.68 The animals were given either a control or a UMP-supplemented diet, and assessed for learning and memory skills. As expected, the impoverished animals fed a control diet did poorly on memory-dependent learning tasks, but those deficits were dramatically prevented in the UMP-supplemented group. One result of studies such as this one is the now-routine addition of UMP to infant formulas to promote healthy brain development.69

Declining ability to produce or respond to the neurotransmitter acetylcholine is one of the hallmarks of Alzheimer’s disease and other disorders of memory. In 2007, the MIT research group found that they could increase acetylcholine concentrations in aged rats with UMP supplementation.70 This is a stunning finding, since drugs like Aricept® that are used to treat Alzheimer’s disease work by inhibiting the enzyme that breaks down acetylcholine—an approach that has had mixed success and may cause serious side effects.71

The same MIT researchers, partnering with Turkish neuroscientists, have recently shown that UMP, together with the omega-3 fatty acid docosahexaenoic acid (DHA), can restore function in an animal model of Parkinson’s disease as well.72 And the same team demonstrated in late 2008 that they could actually enhance the learning and memory improvements caused by DHA in gerbils by adding UMP to the supplementation.73 They concluded, “these findings demonstrate that [UMP/DHA supplements] can enhance cognitive functions in normal animals” (emphasis added).74 In other words, one needn’t already have cognitive impairment to enjoy the potential benefits of UMP supplementation on learning and memory—and who wouldn’t want better memory even at baseline?

Promoting Youthful Cognitive Function With Pregnenolone

Ensuring optimal levels of pregnenolone is another crucial aspect of supporting nervous system health with aging. Derived from cholesterol, pregnenolone acts as a precursor for numerous key hormones in the body including dehydroepiandrosterone (DHEA), estrogen, progesterone, and testosterone.94

With aging, individuals experience a dramatic decline in pregnenolone production, as well as in the hormones for which pregnenolone is a precursor.95-97 Decreasing levels of these essential hormones have been linked with many disorders that commonly accompany aging.

Scientists believe that pregnenolone is intimately connected with cognitive performance. In fact, pregnenolone directly influences release of the crucial neurotransmitter acetylcholine in regions of the brain linked with memory, learning, cognition, and sleep-wake cycles. Furthermore, administration of pregnenolone reverses the decline in new nerve growth (neurogenesis) that commonly occurs in disorders like Alzheimer’s disease. Pregnenolone particularly enhances nerve cell growth in the hippocampus, the brain region responsible for memory, which undergoes marked deterioration in Alzheimer’s patients.98,99

Supplemental pregnenolone may thus support youthful cognition and health by contributing to optimal hormone levels, supporting acetylcholine activity, and promoting nerve cell growth in the brain’s memory center.

Because pregnenolone may affect hormone levels, those with hormonally related cancers such as prostate or breast cancer should avoid using pregnenolone.

Ashwagandha Relieves Stress, Enhances Cognition

Numerous herbs from ancient India are reputed to promote physical and mental health, improve defense mechanisms of the body, and enhance longevity. Among the most promising of these for promoting cognitive health is a plant known as ashwagandha.

Indian researchers characterized the powerful antioxidant capabilities of ashwagandha extracts in 1997, showing that they increased concentrations of natural antioxidants in animal brains after supplementation.75 These researchers concluded that their findings explained the anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging effects reported by other researchers in animal and clinical studies.

The same group later found that they could reduce the chronic stress effects of a mild, unpredictable foot shock in rats if they first supplemented them with ashwagandha extracts.76 Untreated animals experienced elevated blood sugar, glucose intolerance, increased stress steroid levels, gastric ulcers, male sexual dysfunction, cognitive deficits, and depression—common findings in humans exposed to chronic stress—but administration of ashwagandha extracts an hour before shocks dramatically attenuated all of these outcomes. As we noted with phosphatidylserine above, reduced stress allows increased focus on tasks and therefore better cognitive performance, in addition to simply improving quality of life.

Herbal Extracts Spice up Memory

A different Indian scientific group studied ashwagandha in diabetic rats, reasoning that the memory impairment seen in diabetes is in part related to oxidative damage in brain regions that are pivotal in memory and the ability to detect and process new information.77 They found a significant increase in production of oxidation end products in those brain regions, and a decrease in cognitive function, after the rats became diabetic. But following supplementation, the oxidative damage in the relevant brain regions was significantly reduced, as were blood glucose levels. Dramatically, memory impairment and motor dysfunction were also improved in the supplemented animals.

In 2007, further support for the use of ashwagandha extracts in Alzheimer’s disease was provided by the discovery that the extracts are among the most potent inhibitors of acetylcholinesterase, an enzyme that breaks down the vital memory-related neurotransmitter acetylcholine.78 Drugs that block acetylcholine breakdown (such as Aricept®) are utilized in the management of Alzheimer’s disease. The researchers correctly observed that “these results partly substantiate the traditional use of these herbs for improvement of cognition.” Western research into the benefits of ashwagandha is very recent, so stay tuned for additional exciting news on this extract’s memory- and cognition-enhancing properties.

Herbal Extracts Spice up Memory

It is now apparent that many traditional spices, in addition to adding interest to our food, can provide vital anti-inflammatory and antioxidant function that is having an impact on how we think about chronic illness and aging.79 Three of these in particular deserve special mention for their powerful effects on learning and memory.

Ginger is an age-old part of Asian kitchens and pharmacopeias,80 and we focus on it here especially for its ability to regulate platelet aggregation, which contributes not only to cardiovascular disease but also to cerebrovascular disease risk.81-84 Experimental studies demonstrated early in the millennium that ginger extracts could protect cells from the inflammatory action of the Alzheimer’s disease-related protein amyloid-beta.85-87 By its blood pressure-lowering effects, ginger can protect against the chronic brain injury caused by hypertension.82

Rosemary is an herb more familiar in Western kitchens, but has an equally distinguished record as a neuroprotectant through its antioxidant constituent, carnosic acid.88 Rosemary extracts block damaging lipid peroxidation, the destruction of brain cells’ fatty membranes that impairs cognitive performance.89 Rosemary also protects cell nuclei from DNA damage that results from both oxidant stress and ultraviolet light90—such damage is at the root of many cancers, but short of cancer it can impair a cell’s ability to function normally.

Neuroscientists in England recently showed a remarkable capacity of rosemary: humans exposed just to the aroma of its essential oil performed significantly better on overall memory quality compared with controls.91 Subjects also had increased states of alertness compared with controls or those exposed to lavender aroma.

Completing the culinary triad of memory-enhancing herbs is hops, the bitter ingredient of beer. Hops’ value may be primarily in its ability to promote relaxation and sleep—in one study, the combination of hops with valerian compared equally with a Valium®-like, sleep-inducing drug, and had none of the “hangover” effects seen with the drug.92 Similar results were found in another study comparing a Valium®-like drug with a hops/valerian combination: both groups did equally well on sleep, relaxation, and quality of life improvement, but patients experienced withdrawal symptoms when they stopped taking the drug.93


Far from being an “inevitable” consequence of aging, we now understand that cognitive decline and memory deficits are the predictable results of a lifetime of oxidative and inflammatory injury that damages brain cells’ ability to communicate with one another. A vast array of valuable nutrients are available to help block that damage—and in some cases to actually reverse it. Strong evidence abounds that the nutrients described in this review have important roles in improving the quality of life of older adults, keeping their wits sharp and their experiences vivid. These nutrients together, therefore, make up a vital part of any long-term brain health regimen.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.


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