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Life Extension Magazine

LE Magazine October 2005
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Preserving and Restoring Brain Function

By Dale Kiefer

Protecting brain health is vital if the pursuit of a longer life is to have any meaning. According to current wisdom, some degree of cognitive impairment is all but inevitable as we age.1-6 That is, unless steps are taken to prevent it.7-12

Scientists in Texas recently noted, “As life expectancy increases worldwide, pandemics of cognitive impairment and dementia are emerging as major public health problems.”2 Another research team tried to inject humor into this sobering topic:

“Cognitive aspects of aging represent a grave challenge for our societal circumstances as members of the baby-boom generation spiral toward a collective ‘senior moment.’”5

The encouraging news is that scientists have discovered methods to preserve and even restore neurological structure and function. These powerful weapons give aging adults unprecedented control over their cognitive health.

Recent data indicate that up to 9.4% of Europeans over the age of 65 suffer from some form of dementia.13 A report from Great Britain notes that the incidence of cognitive impairment may increase dramatically with age.14

Cognitive impairment was detected in 18.3% of subjects in a study of more than 15,000 elderly in the United Kingdom, approximately half of whom were 75-79 years old.14 French researchers noted recently, “In most countries, the prevalence of dementia varies between 6 and 8% for individuals aged 65 years or more. It then dramatically increases with each subsequent decade, reaching around 30% of the population aged over 85.”15

Unfortunately, these statistics fail to estimate the incidence of mild cognitive impairment (MCI). Subtler than dementia, MCI is also undoubtedly more prevalent. MCI, defined as an intermediate state between normal aging and dementia, is characterized by “acquired cognitive deficits, without significant decline in functional activities of daily living.”16 In Australia, a small study attempted to identify the prevalence of MCI without dementia among community-dwelling elderly aged 70-79. One third of the subjects showed evidence of the condition.17

Researchers in Germany studied more than 1,000 elderly adults aged 75 and older. “Mild cognitive impairment is very frequent in older people,” they concluded. Prevalence rates ranged from 3% to 36%, depending on the diagnostic criteria applied. Over the course of about 30 months, up to 47% of those identified with MCI progressed to dementia.18

Strategies for Protecting the Brain

Cognitive decline is not inevitable with advancing age. It is possible to live a longer and healthier life, but preserving brain health is crucial to accomplishing this goal. Various factors conspire to rob us of mental acuity as we age. Recent studies suggest that inflammation (as determined by elevated levels of interleukin-6 or C-reactive protein), high blood pressure, high blood insulin, excessive body weight or obesity, arterial stiffness, and the increasingly common condition known as metabolic syndrome (characterized by a cluster of abnormal conditions such as insulin resistance, obesity, high cholesterol, and hypertension) are all independent risk factors for dementia.19-24 Psychological health, including anxiety and depression, has recently been implicated as a risk factor as well.25

The ideal strategy for preserving brain function begins with preventing illnesses that may contribute to cognitive decline and dementia. Good nutrition—including dietary supplements—and a healthy lifestyle can keep many of these afflictions at bay. As a first step toward ensuring brain health, keep your blood pressure and weight in check, avoid metabolic syndrome and diabetes, and obtain treatment for depression or anxiety disorders. However, there is much more that can and should be done to protect the aging brain.

Scientists have advanced several theories regarding the causes of cognitive decline associated with advancing age. One familiar hypothesis proposes that toxic by-products of cellular metabolism known as free radicals slowly accumulate within cells, where they cause cumulative and eventually fatal damage.26 Nerve cells (neurons) in the brain rely on the oxidative phosphorylation of glucose within the mitochondria to supply their considerable energy needs. Accordingly, the brain’s appetite for glucose and oxygen is great.27 As a result, the brain is particularly susceptible to oxidative stress. Free radicals are produced by the mitochondria at an accelerated rate. Supplemental antioxidants, therefore, are especially important to preserving healthy cognitive function.10

The Cholinergic System at Risk

Inflammation is also implicated in the development of various neurological disorders, including Alzheimer’s disease and vascular dementia. It is believed that inflammation triggers a cascade of events that leads to the destruction of neurological tissues.28 In Alzheimer’s disease, the presence of a protein, beta-amyloid (Abeta), appears to trigger inflammation.29 A decline in acetylcholine, an important messenger chemical or neurotransmitter, has also been observed in individuals with Alzheimer’s disease.30 Early on, this inflammation and cholinergic dysfunction may be experienced as mild memory impairment or confusion. Left unchecked, however, it invariably leads to advancing cognitive decline and dementia. Anti-inflammatory strategies thus make sense in protecting cognitive function.

Interruptions in cerebral blood flow have also been implicated in cognitive decline,31,32 so optimizing blood flow is a logical strategy for protecting brain function. Vascular dementia was once considered distinctly different from Alzheimer’s-type dementia, but scientists now believe that vascular dementia and Alzheimer’s share a common pathology—namely, the disruption of cholinergic function.33 Even decreasing psychological stress may be helpful. New research shows that older men who secreted the highest levels of epinephrine (a stress hormone) were more likely to suffer subsequent cognitive decline.34 While body cells are easily replaced, the nerves and supporting tissues of the brain and spinal cord cannot yet be replaced once they are damaged or destroyed. Cells of the brain and nervous system are incapable of further division and renewal once they reach maturity.35,36

Various lifestyle factors contribute to healthy brain aging, including regular exercise and adequate sleep, routine mental stimulation, a positive outlook, and a healthy social network.7,37,38 However, nutritional support for the aging brain likewise is of paramount importance. Supplements that combat inflammation, improve cerebral blood flow, and reverse the loss of acetylcholine and its receptors directly target the causes of age-related brain decline.

GPC Benefits Brain Health

Glycerophosphocholine, or GPC (formerly called L-alpha glycerylphosphorylcholine, or choline alfocerate) is naturally present in all the body’s cells. Its importance to life and safety as a supplement are evidenced by its substantial presence in human breast milk.39,40 First discovered in the late 1990s, GPC is now regarded as essential to the healthy development of newborns, due to the great demand for choline, especially by the rapidly developing brain.40

Among aging adults, the rationale for GPC therapy goes back to the hypothesis, developed more than 30 years ago, that declining levels of acetylcholine—and a concurrent decrease in the number of neurons that are its intended target—are responsible for a range of cognitive deficits.29 Acetylcholine is an essential neurotransmitter involved in muscle control, sleep, and cognition. Its decline coincides with advancing age, and is a hallmark of the neurodegeneration seen in cognitive decline, vascular dementia, and Alzheimer’s disease. By boosting acetylcholine levels in the brain, the hypothesis proposes, it should be feasible to reverse these cognitive deficits and changes in brain structure.1

Early attempts to identify a suitable precursor for acetylcholine failed until scientists experimented with GPC.41-44 Sold in Europe by prescription only, GPC is available in the US as a dietary supplement. GPC provides a crucial building block for the production of new acetylcholine in the brain. Numerous clinical trials have scrutinized the efficacy and safety of GPC in humans and in animal models of human neurological disorders.45-48 These studies, large and small, controlled and informal, have universally demonstrated GPC’s effectiveness, safety, and tolerability.1,49,50 The studies have examined everything from changes in learning, memory, and brain structure in rats, to stroke-induced cognitive deficits in humans, to induced and restored memory deficits in laboratory animals.1,45-51

In early 2001, a retrospective analysis of published clinical data involving 4,054 patients concluded that, overall, GPC improved patients’ clinical conditions. Of the 10 studies devoted to dementia disorders, a majority were controlled trials that compared the efficacy of GPC to either placebo or a reference drug. Dr. Lucilla Parnetti, a coauthor of the analysis, wrote, “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.”1

Early clinical trials with GPC used daily dosages of 1200 mg. After an initial two to four weeks at this dose, some people reduce their dose to 600 mg daily. A daily dose of 300 mg may be appropriate for healthy young people.

GPC works in a manner roughly similar to prescription cholinesterase inhibitor drugs such as donepezil (Aricept®) and rivastigmine (Exelon®), which are used to combat acetylcholine deficits in Alzheimer’s and vascular dementia patients.52 However, GPC tackles the problem of too little acetylcholine from a different angle. Rather than interfering with the enzyme that breaks down acetylcholine, GPC provides a means for the body to manufacture new acetylcholine.

Ashwagandha (Withania somnifera)

Ashwagandha and the Brain

Ashwagandha is a medicinal plant used in India to treat a wide range of age-related disorders.53-63 Its most remarkable effect may involve its ability to preserve the health of the aging brain.

Ashwagandha offers myriad neuroprotective benefits. For example, one study showed that when given to mice, ashwagandha extract promotes memory retention, even when amnesia has been induced experimentally.60 Another study found that ashwagandha extract is capable of protecting the brains of laboratory rats against experimentally induced stroke.61 Ashwagandha constituents have also been shown to inhibit acetylcholinesterase (AChE), an enzyme responsible for breaking down acetylcholine, the neurotransmitter that is in dangerously short supply in the brains of Alzheimer’s disease sufferers.62 This AChE-blocking action is similar to that of prescription drugs such as Aricept® that are currently used to treat Alzheimer’s symptoms.

Exciting new research indicates that ashwagandha extract is capable of halting and even repairing damage to brain cells in an experimentally induced model of Alzheimer’s disease.63 Scientists in Japan induced Alzheimer’s-type brain cell atrophy and loss of synaptic function in mice by exposing them to the toxic protein Abeta, which has been implicated in the genesis of Alzheimer’s disease in humans. “Subsequent treatment with [a constituent of ashwagandha] induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons,” according to the scientists.63

Phosphatidylserine Maintains Brain Cell Membranes

Phosphatidylserine, a natural and integral component of every cell membrane, is a powerful weapon in the fight against brain aging. Phosphatidylserine is sold in Europe and Japan as a regulated drug, where it is often prescribed to combat memory loss and learning deficits. Available as a nutritional supplement in the United States, phosphatidylserine serves as a key component of many brain function-enhancing formulas.

The body manufactures phosphatidylserine to ensure its continual supply, underscoring the importance of this natural phospholipid. Unfortunately, however, aging slows production of this crucial contributor to brain health.

Phosphatidylserine helps the brain use its fuel efficiently. By boosting glucose metabolism and stimulating production of acetylcholine, supplemental phosphatidylserine has been shown to improve the condition of patients experiencing age-associated memory impairment or cognitive decline.8,64-67 Clinical trials using small groups of patients with cognitive decline demonstrated significant improvements with phosphatidylserine supplementation, especially among patients in the early stages. Positron emission tomography (PET) brain-imaging scans verified that patients taking phosphatidylserine experienced significant increases in glucose uptake compared to subjects who received social support or cognitive training but not phosphatidylserine.68

A large multicenter trial examined the use of phosphatidylserine to combat the effects of moderate to severe age-related cognitive decline. Patients were drawn from 23 general medicine or geriatric units. Compared to patients who received dummy placebo pills, phosphatidylserine-supplemented patients demonstrated significant behavioral improvements, including increased socialization, motivation, and initiative.69

Phosphatidylserine is generally safe and well tolerated, with no significant drug interactions reported.70

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