Cognitive Deficit Treatment
Cognitive assessment and treatment have been covered at length in previous issues of Life Extension (see, for example, “Inflammation and the Aging Brain,” September 2003, and “Life Extension for the Brain,” March 2004). Treatment of cognitive degeneration focuses on cholinergic medications and supplements. Typical medications for cognitive degeneration include Aricept®, Prostigmin®, tacrine, and Exelon®. Supplement support should include choline, phosphatidylserine, vinpocetine, and quercetin, available in formulations such as Cognitex.
Dietary support includes food rich in choline such as eggs, wheat germ, blueberries, broccoli, almonds, and caviar.
Knowledge of the cellular processes involved in Parkinson’s has opened new fronts in the battle against the disease. Pharmaceuti-cal advances have had marked positive effects in Parkinson’s disease patients, but side effects, subtherapeutic effects, the need for increased dosages, and eventual drug ineffectiveness after long usage temper drug efficacy. Pharmaceutical intervention is usually delayed until absolutely necessary.
When Parkinson’s disease progresses, levodopa increases dop-amine, which improves motor symptoms. Bradykinesia and rigidity are more likely to ameliorate than tremor, while there is usually no improvement in postural stability, mental state, or autonomic nervous system dysfunction. Side effects include nausea and vomiting, which can be mitigated with a decarboxylase inhibitor such a carbidopa. Dyskinesias (abnormal involuntary movements) also can occur, with additional effects on speech, swallowing, respiration, and balance.31 Levodopa invariably presents dosage issues, as too much causes side effects and too little causes an early “wearing off” with a return of motor dysfunctions.
Pharmaceutical approaches now include the use of dopamine agonists before levodopa is used. Agonists improve dopamine receptor activity that facilitates the transport of dopamine. Drugs such as ropinirole are less likely than levodopa to lead to motor fluctuations and dyskinesias, but their effectiveness wanes after three years.26 At that time, a combination therapy using levodopa and an agonist is initiated. This protocol allows lower dosages of levodopa, and shows positive motor effects.32
Catechol-O-methyltransferase has been linked to motor fluctuations and dyskinesias, so its inhibition can extend the therapeutic effects of levodopa. Entacapone and tolcapone have been shown to reduce both motor fluctuations and levodopa “off” time.33-35
To address oxidative stress, selegilene (Eldepryl®), a monoamine oxidase (MAO) inhibitor, is prescribed in Parkinson’s disease and can delay the evolution of disability.36 Early use of an agonist could also have a neuroprotective effect.37
Doctors prescribe drugs such as benztropine and amantadine to counteract dyskinesias and relieve tumors. Because their adverse effects include cognitive impairment, however, these drugs should be used with caution in patients over the age of 70.
Excitotoxicity is mitigated by the use of antiglutamatergic agents such as N-methyl-D-aspartate (NMDA) receptor antagonists and calcium channel blockers such as Procardia®.38 Common medications such as Celebrex® and Vioxx® inhibit the cyclooxygenase type 2 (COX-2) enzyme, which has been implicated directly with the inflammation associated with Parkinson’s disease.39
vitamin B6, zinc, DHEA
Vitamins C and E,
polyphenols, bioflavanoids, proanthocyandins,tocotrienols, curcumin, glutathione
holy basil, thunder God vine, Nexrutine®
Readily available natural alternatives address many of the cell death processes related to Park-inson’s disease and have shown dramatic results (see case study on p. 72). Such approaches are particularly efficacious in the early stages of the disease, when symptoms first appear but drugs are not yet indicated. Moreover, natural supplements are well tolerated, without the side effects associated with prescription medications.
Tyrosine and phenylalanine are amino acid precursors to dopamine, available from protein food sources and supplements.40 Because protein interferes with levodopa absorption, its intake should be limited to one meal when a course of medication commences. Vitamin B6, zinc, and the adrenal hormone DHEA also have been shown to increase dopamine formation in the brain.41,42
If levodopa (Sinemet®) is used, vitamin B6 should be taken 3-4 hours after the last dose of levodopa, since vitamin B6, in some cases, may cause levodopa to convert to dopamine in the blood before it reaches the brain. “There are so many cellular factors involved with Parkinson’s that we have to enlist every possible means of support to fight it,” notes Eric Braverman, MD, director of New York City-based PATH Medical and an expert on brain-related illnesses. “Nutrition cannot be underestimated, and there’s a whole dopamine diet available to Parkinson’s patients. Even when physicians didn’t know what dop-amine was, they treated Parkinson’s symptoms with a diet rich in fava beans (a natural source of levodopa), and it helped.”
A major focus in treating Park-inson’s disease is reducing oxidative stress, and alternative approaches are instrumental in this regard. Intravenous infusion of chelators eliminates from the brain iron and other toxins that contribute to the formation of free radicals. Antioxi-dants also act as chelators, and best results are achieved when a combination is used. Alternatives include vitamins C and E, polyphenols found in green and black teas, bioflavanoids that provide the red, pink, and purple colors in flowers, fruits, and vegetables, proanthocyandins from grape seed extract, tocotrienols from palm oil, and curcumin.43-45
Of particular interest in Park-inson’s disease is the role of glutathione, a metabolite of the essential amino acid methionine. Glutathione is contained in the cells of all living organisms. A billion years before life appeared on earth, when the atmosphere was gaseous and toxic, cells had to incorporate antioxidants like glutathione to survive. Glutathione also assists with the transport of amino acids across cell membranes.46
Glutathione is not readily obtainable from food sources, but is available in supplements and can be introduced directly via an IV infusion. Adequate levels of glutathione in the body depend on cysteine, glycine, and glutamic acid. Of these, only cysteine ever seems to be in short supply. Cysteine is derived from methionine, an essential amino acid that transports methyl groups and sulfur into the body to form proteins. To ensure adequate glutathione, one may eat foods rich in sulfur, such as egg yolks, red peppers, and onions. Another way to raise glutathione levels is to supplement the body’s cysteine with N-acetylcysteine or L-cysteine.46
• Nutritional support
• Cognitive assessment
• Conventional approaches
• Natural alternatives
Metabolic support for mitochondria has been demonstrated with phosphatidylserine, acetyl-L-carnitine, and coenzyme Q10.47 A recent study links creatine, an amino acid compound of methionine, glycine, and arginine, with mitochondria metabolism.48
As for nonprescription anti-inflammatory alternatives, the options are many. Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and Motrin® have proven efficacy in Parkinson’s disease.49 Green and black teas also reduce swelling, as do herbs such as thunder god vine and holy basil.50 Phellodendron amurense extracts have been used in traditional Chinese medicine and have been proven to inhibit COX-2 activity.51 These extracts are available in Nexrutine®.
Magnesium and the amino acid tryptophan, found in turkey, bananas, and milk, mitigate the dyskinesia that can occur with dopamine therapies.52
Finally, as with any neurological complaint, gentle stimulation introduced with cranial electrical stimulation (CES) or transcranial magnetic stimulation (TCMS) units can keep circuits open and mitigate motor disconnect symptoms.
With so many natural alternatives for relief of Parkinson’s disease symptoms, more serious medical approaches can be postponed until absolutely necessary, as described below.
When Parkinson’s disease has progressed such that it can no longer be managed using supplements and medications, two options remain.
The first, ablative surgery, disconnects areas in the brain responsible for muscle movement. Destructive surgery relieves rigidity, bradykinesia, and tremors. Sypmtom relief occurs in less than 90% of patients, but is complete and unilateral. Surgical complications include cerebral infarction, difficulty swallowing, cognitive impairment, and visual field defects.53 Thus, ablative surgery is indicated only in patients with a long history of tremor that cannot otherwise be controlled.
The second option, deep brain stimulation, involves placing an electrode into the thalamus with a connection to a pulse generator implanted in the chest. Deep brain stimulation regulates muscle movement. Its advantages are that it is reversible and will not preclude the benefit of future remedies; its disadvantages include its cost, discomfort, risk of infection, and need for replacement.54
New drugs for Parkinson’s disease are constantly being evaluated. Among the clinical trials under way at the National Institutes of Health are those related to cognitive decline, depression, and sleep disorders. A new transdermal patch could provide more controlled drug delivery so that the problems of overdosing or “wearing off” can be avoided.
Information related to Lewy bodies (abnormal structures found in certain areas of the brain) and glutathione may prove to be significant for developing an early-warning marker for Parkinson’s disease. Patients with incidental Lewy bodies do not have Parkinson’s symptoms but are thought to have early Parkinson’s disease. These same patients have reduced levels of glutathione, so perhaps this combination will lead to a test that can identify those most at risk.55
Further research into the importance of trophic factors may have a major impact on the treatment of Parkinson’s disease.56,57 These factors, such as glial-derived neurotrophic factor and brain-derived neurotrophic factor, are important for neuron protection and nutrition. Before they can be clinically used, however, issues relating to their delivery to specific brain regions, dosages, and factor selection must be resolved.
Finally, two highly experimental Parkinson’s disease treatments now under investigation are transplanted grafts of adrenal or other tissue from fetuses or other species into the SNc to promote dopamine production, and gene therapies for maintaining the integrity of mitochondria cell membranes. Stem cells that would replace dopamine-producing neurons offer great promise.
For all that remains unknown about Parkinson’s disease, much can be done to counter its effects. First is the proper diagnosis and identification of contributing factors related to each case. Next is proper counseling and education. Finally, a global plan that incorporates lifestyle, diet, and treatment options, with initial and continuing emphasis on natural alternatives, must be formulated, administered, and monitored by experienced health care personnel. With such a plan, the Parkinson’s patient can successfully fight a stalling action until new research results in a definitive cure.