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Life Extension Magazine

LE Magazine July 2003

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Preserving Brain Function with GPC

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Fear of Alzheimer's disease, with its relentless erosion of memory and personality, gnaws at the edges of baby boomers' minds just as surely as they are aging. A little uneasiness is understandable, given that the primary risk factor for developing Alzheimer's disease (AD) is age.1,2 After all, no one wants to lose her mind. Risk of succumbing to dementia is relatively small in early old age, but the odds climb inexorably with each passing year. And there is evidence that some cognitive decline is inevitable in the elderly, even in the absence of other diseases such as Alzheimer's.3

In the developed world, it's estimated that dementia afflicts just 1.5% of the population at 65 years. But dementia increases exponentially: by 80 years of age 30% will be stricken.4-7 Dementia may or may not be associated with concurrent AD. For reasons that remain unclear, dementia associated with AD strikes females more commonly than males, and AD dementia is more common in the developed countries of the West.

Vascular dementia is a term used to describe loss of mental function due to pathologies of the cerebrovascular system. Stroke is but one example. All such pathologies involve interruptions of normal blood flow to the brain. Hope on the horizon

Fortunately, researchers have discovered some compounds that may slow, halt, or even reverse the otherwise relentless deterioration of brain structures that begins with mild cognitive impairment and often progresses to the full-blown dementia of Alzheimer's disease or vascular dementia. One promising newer compound is an acetylcholine precursor derived from soy: L-alpha glycerylphosphorylcholine (GPC). The brain converts GPC into acetylcholine, an essential neurotransmitter whose decline is centrally implicated in brain aging and neurodegeneration.

Available only by prescription in Europe, where it is sold under the trade name, Gliatilin, GPC is currently available to Americans as an over-the-counter dietary supplement. It is a derivative of the natural compound phosphatidylcholine. Interest in GPC among gerontologists, neurologists and other researchers appears to be growing. As the vast baby boom generation continues to age, GPC may well become a popular hedge against the forgetfulness and confusion that inevitably afflict the elderly.

Make no mistake: researchers generally agree that even the sharpest (and most fortunate) of minds will eventually experience some decline in normal thought or cognition due to the ravages of old age. Even in the absence of concurrent diseases such as AD or vascular dementia, we can all expect to experience some decline in memory, attention and general cognition as we age, if steps are not take to intervene. 3,11

A call for early intervention

Late last year, in an article published in the highly respected British medical journal, The Lancet, authors Alistair Burns M.D. and Michael Zaudig M.D. argued that memory complaints are "an almost universal early symptom of dementia". Furthermore, say the authors, "mild cognitive impairment defines a transitional stage between normal aging and dementia."19,20 They note that 25 million people across the globe are afflicted with dementia. Mild cognitive impairment "represents an opportunity for early intervention," say Burns and Zaudig. They believe that mild cognitive impairment deserves additional attention from the medical community as a target for early dementia-prevention strategies. They suggest that doctors should take complaints of memory loss more seriously. They note that memory difficulties represent an early warning sign identifying patients who may be at high risk of developing dementia.

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Lucilla Parnetti M.D., PhD, an Italian neuroscience researcher who co-authored a retrospective analysis of GPC research, shares Burns' and Zaudig's faith in early intervention. Dr. Parnetti believes that a firm case can be made for pre-emptive treatment with GPC. She notes that early acetylcholine depletion and cholinergic receptor demise begins approximately in the fourth or fifth decades of life, progressing thereafter. Is it possible that GPC may be capable of preventing these detrimental conditions of aging outright? Dr. Parnetti says, "It might be." Her guarded optimism is understandable. Research into intervention therapy is ongoing, and much work remains to be done.

Why it works

It's long been established that aging brains are characterized by a deficiency in the neurotransmitter acetylcholine. Aging brains also lose cholinergic receptors; structures within the nerves that receive and propagate the messages transmitted by acetylcholine.10 The resulting erosion of memory may be exaggerated by the presence of other pathological conditions such as Alzheimer's disease, or vascular dementia.3

Acetylcholine is an extremely important messenger molecule that facilitates numerous activities within the brain, particularly in areas associated with memory, learning and attention. In the body, acetylcholine is crucial to muscular control. Among Alzheimer's patients with dementia, acetylcholine transmission in the hippocampus is severely impaired. Cholinergic neurons die at an increasingly rapid pace, with dementia the inevitable dreaded result. Even in otherwise healthy people, short-term memory loss and declining thought processes may be due to the malfunctioning of this messenger/receptor system. The rationale for GPC therapy goes back to a hypothesis, developed more than three decades ago, that a decline in this important neurotransmitter - and a concurrent decrease in the number of neurons that are its intended target - is responsible for a range of cognitive deficits.10 By artificially bolstering acetylcholine levels in the brain, researchers reasoned, we might be able to reverse those cognitive deficits and brain structure changes.3

Scientists enthusiastically investigated the potential therapeutic benefits of natural acetylcholine precursor compounds such as lecithin and choline, but results were disappointing.11-14 Choline in particular appeared to hold great promise initially. In the body choline serves not only as a precursor to acetylcholine, but also as one of the building blocks for phosphatidylcholine, a phospholipid that is an important component of brain cell membranes. Without it, membranes lose structural integrity and neurons wither.

The body partially compensates for acetylcholine deficits by "raiding" existing phosphatidylcholine for conversion to acetylcholine. While it's an intriguing example of the body's remarkable adaptability and economy, this reallocation ultimately serves only to weaken cell membrane integrity by depleting phosphatidylcholine stores.

Soon after it became clear that choline and lecithin were not significantly reversing cognitive decline, researchers began looking at GPC. Results were dramatically different. Finally, a precursor with the ability to rejuvenate acetylcholine levels, receptors, and neuronal structural integrity had been discovered.

Numerous clinical trials have scrutinized the efficacy and safety of GPC in animal models and in humans.16-18 These studies - large and small, controlled and informal - have universally demonstrated favorable results and an excellent safety and tolerability profile.3 Past studies have looked at everything from changes in learning, memory and brain structure in rats, to stroke-induced cognitive deficits in humans, to induced - and restored - memory function deficits in laboratory animals.

By early 2001, a retrospective analysis of published clinical trials involving 4,054 patients found that overall, GPC improved patients' clinical conditions.3 A majority of the ten studies devoted to dementia disorders were controlled trials that compared the efficacy of GPC to either placebo or a reference drug. Lucilla Parnetti, MD, PhD, co-author of the analysis writes, "Administration of [GPC] significantly improved patient clinical condition…results were superior or equivalent to those observed in control groups under active treatment and superior to the results observed in placebo groups."

GPC has been directly compared to some popular, alledgedly nootropic (or brain-enhancing) substances; oxiracetam and acetyl-L-carnitine. Cognitive improvement scores among GPC patients were similar to those seen in patients taking oxiracetam.29 Tests comparing the efficacy of GPC versus acetyl-L-carnitine demonstrated that GPC delivers superior cognitive benefits.30

Research on GPC's therapeutic effect in cases of vascular dementia caused by stroke suggests that GPC may well promote functional recovery. These studies, involving 2,484 patients in three trials who had suffered cerebrovascular stroke and/or transient ischemic attacks were uncontrolled, however, so additional research is in order to fully establish GPC's efficacy in these situations.3

Continued on Page 2 of 2

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