Overview and Risk Factors
Parkinson's disease (idiopathic paralysis agitans) is a progressive, degenerative disorder of the brain that is associated with a loss of dopaminergic neurons in the substantia nigra, neurodegeneration in other areas of the central nervous system (CNS), such as the locus ceruleus and the cerebral cortex, and the presence of Lewy bodies. Loss of dopamine stimulation causes an imbalance between excitation and inhibition pathways of the basal ganglia (that coordinate motor activity), resulting in impairment in the voluntary control of movement.
Hallmarks of the disease include muscular ("cogwheel") rigidity, slowed initiation of movement (bradykinesia), and an unstable, flexed posture. Despite instability, the gait is narrow-based. A resting tremor that decreases with movement appears in about 2/3 of patients and most often manifests in a classic "pill-rolling" tremor of the thumb and forefinger. This tremor disappears with the initiation of movement, only to return with sustained postures or rest. Patients exhibit a shuffling gait and slowed movements and usually show progressive difficulties with activities of daily living (eg, eating, dressing, writing). Depression is common, and hallucinations may appear with more advanced disease, sometimes as an adverse side effect of medications used to treat the condition. Dementia occurs in about one-third of cases and often appears as Alzheimer's disease. However, prominent hallucinations may indicate diffuse Lewy body disease. Autonomic dysfunction, including postural hypotension, is common late in the course of disease.
Most cases are idiopathic. However, there are many conditions that present as parkinsonism, most of which do not include tremor. Some of these are degenerations of the basal ganglia systems, but without dominant degeneration of substantia nigra seen in idiopathic Parkinson's. Parkinsonism may also result from exposure to toxins (MPTP, a contaminant of poorly synthesized opioid narcotics; pesticides; manganese toxicity), head trauma, CNS infection, or postsynaptic dopamine-receptor blockers, such as antiemetics, antipsychotics, and reserpine.
Age. About 1% of Americans over age 50 are affected, and prevalence increases with age. Typical age of onset is the late 50s, although 10% of cases present before age 40.
Genetics. Although genetics has been postulated to play a role, familial disease is rare.
Diagnosis and Treatment
Diagnosis of Parkinson's disease is generally made by the characteristic clinical presentation, including history, physical examination, and neurologic examination.
Although there are no commonly available confirmatory tests or imaging modalities, clinical response to a dopamine agonist strongly suggests the diagnosis.
A CT scan, MRI, and/or laboratory testing may be indicated in equivocal cases to rule out other diagnoses (Wilson's disease, Huntington's disease, cerebrovascular disease, normal pressure hydrocephalus, mass lesions). However, imaging is generally only indicated if the presentation is atypical or if focal symptoms are present.
Parkinson's disease follows a progressive course. The disease advances in all cases, but the rate of progression varies, with younger patients typically progressing more rapidly. While there is no definitive cure available, medical treatment can alleviate many of the symptoms.
Physical, occupational, and speech therapies are often beneficial, and social work consultation can help make daily living at home easier for the patient and prevent further disability.
Medications that might cause parkinsonian symptoms should be discontinued and alternative drugs used if necessary. Treatment is primarily aimed at increasing the availability of dopamine to the CNS.
Levodopa (a dopamine metabolic precursor) plus carbidoba (which antagonizes the catechol-O-methyltransferase enzyme that would otherwise inactivate levodopa prior to reaching the brain) have proven to be the most effective therapy to improve symptoms. However, the drugs do not seem to affect the disease's progression.
Catecholamine-O-methyl-transferase (COMT) inhibitors (entacapone, tolcapone) may slow the breakdown of dopamine, which is often helpful if the effect of levodopa is too short. It is prudent to be aware of potential liver toxicity with use of tolcapone.
Dopamine agonists may improve symptoms (bromocriptine, pergolide, pramipexole, ropinerole). Pergolide can contribute to fibrosis.
Selegiline impedes the breakdown of dopamine and may also prolong the action of levodopa.
Amantidine may be useful for its mild anti-parkinson's effects, but also as a mild psychostimulant and a treatment for dyskinesias.
Symptomatic treatment may be useful for hallucinations (clozapine, quietiapine), severe dyskinesias (amantadine), and tremor (benztropine).
Surgical approaches (thalamotomy, pallidotomy, subthalamic deep brain stimulation) may have a role in advanced disease, especially in patients with severe intractable dyskinesia, tremor, or rigidity.
Nutritional links to Parkinson's disease have been identified, although the mechanisms explaining these associations are not entirely clear.
Nutritional Factors in Prevention
In epidemiologic studies, the following factors have been associated with reduced risk of developing Parkinson's disease:
Low-fat diets. The prevalence of Parkinson's disease correlates with intake of animal fat,1,2 and with total and saturated fat.3
Minimizing dairy intake. The Health Professionals Follow-Up Study found a higher risk for Parkinson's disease in men with high intakes of dairy products (roughly 3 servings per day).4 Positive associations between dairy products and Parkinson's were found for dairy protein, dairy calcium, dairy vitamin D, and lactose, and not for other sources of these nutrients. Researchers suggest that tetrahydroisoquinolines found in dairy products may be a potential cause of this disease, due to their ability to cross the blood-brain barrier and induce degeneration of dopaminergic neurons in experimental models. The presence of dopaminergic neurotoxins, including beta-carbolines and their derivatives, pesticides, and polychlorinated biphenyls found in dairy products, may also be involved.4
Caffeinated beverages. Observational studies have found protective effects of frequent consumption of coffee or tea,5-7 although some evidence suggests that benefits are limited to men, and to women who do not use postmenopausal hormone-replacement therapy.
Nutritional Factors in Treatment
The most immediate nutritional concerns in Parkinson's disease treatment include changes in the absorption rate, blood levels, and CNS uptake of L-dopa. The protein content of meals, and particularly the distribution of protein intake throughout the day, has emerged as an important consideration in the effectiveness of L-dopa for many patients.8-11
Patients with PD have a 4-fold increase in risk for weight loss of 10 lbs or more compared to age-matched controls for a variety of reasons, including dysphagia, dyskinesias, depression, and cognitive impairment; conversely, excess weight gain may occur due to an increase in sedentary behavior.12 Individuals with chewing or swallowing difficulties should be referred to a speech therapist for appropriate changes in diet texture. A registered dietitian can help families plan meals that are also adequate in fluid and fiber (particularly insoluble fiber), an important concern to prevent constipation.12
Timing of protein intake
The first evidence of a role for protein in modulating treatment response to L-dopa came from patient reports of deterioration of drug benefit (the 'on/off' phenomenon) after high-protein meals.10,11 The beneficial effects of a protein-reduced diet, or the redistribution of almost all protein to evening meals on L-dopa availability (and subsequent control of dyskinesias) have been subsequently documented in patients who experience erratic responses to levodopa therapy.8-11 In these studies, reducing protein intake to amounts as low as 10 grams/day (or 0.5g/kg body weight) resulted in an improved therapeutic response in many (though not all) individuals. Low-protein diets resulted in improvements in neurologic scoring.10
Similarly, redistributing all but 7 grams of protein intake to the evening meal resulted in improvement in the Northwest Disability and AIMS Dyskinesia Scale.9 Both low-protein diet and diets reserving protein for evening meals were associated with significant reductions in the need for L-dopa.9,10 A more recent study that both decreased protein intake to the Recommended Daily Allowance (ie, 0.8 g/kg body weight) and distributed almost all protein to the evening meal (through the use of special low-protein starches) demonstrated a similar benefit. Specifically, postprandial and total 'off' phases (consisting of dyskinesias and complaints of pain, parasthesias, sweating, constipation or shortness of breath) were reduced from a mean of 79 to 49 minutes, while total 'off' time was decreased from a mean of 271 to 164 minutes by the protein redistribution diet, reductions of 38% and 39% in 'off' time, respectively.8 In addition, the mid-day dosage of L-dopa was reduced in one -third patients by an average of 9%. Caution may be required because the results of protein redistribution can be so effective that an excess of L-dopa may enter the brain and trigger dyskinesia.13
A protein restriction-induced decrease in requirement for L-dopa may offer more than symptomatic benefit. It is well known that oxidative stress is central to the pathology of PD, and autoxidation of L-dopa increases oxidative stress in the substantia nigra.14 Therefore, any measures that reduce the effective dose of L-dopa may prolong the period during which patients benefit from drug therapy. In addition, high-protein meals raise blood levels of homocysteine,15 a possible risk factor for vascular disease known to be elevated in PD patients as a side-effect of L-dopa.16 Due to the risk of nutrient insufficiencies on such diets,17 multiple-vitamin-mineral supplementation has been suggested.12 Physicians interested in referring patients for a protein redistribution diet that meets both energy and micronutrient needs should contact a registered dietitian who can help patients and families to plan appropriate meals.
The seed powder of the plant Mucuna pruriens contains significant amounts of L-dopa, and has long been used in Ayurvedic (East Indian) medicine for the treatment of movement disorders.18 Although several open trials and one double blind, placebo-controlled trial demonstrated effectiveness, a report by the American Academy of Neurology concluded that there is currently insufficient evidence to support or refute the use of Mucuna pruriens.19 However, considering the commercial availability of Mucuna pruriens, in addition to the growing number of East Indian immigrants to the US,20 it is not unlikely physicians may encounter patients who are using this product.
Oxidative stress and Parkinson's disease
Several factors have led to the theory that oxidative stress contributes to the risk for development of Parkinson's disease,21 possibly by causing mitochondrial decay.22 This has resulted in trials of both medications that inhibit oxidation as well as of supplements that scavenge free radicals.
Vitamin E. There is good evidence that dietary vitamin E intake is inversely correlated with risk of developing Parkinson's disease, and lower levels of vitamin E have been found in the cerebrospinal fluid of patients with the condition, when compared with patients with other neurological diseases.23 However, vitamin E supplements have not been shown to be effective, either in preventing or slowing the progression of the condition.24
Coenzyme Q10. The neuroprotective effects of coenzyme Q10 (300, 600, or 100 mg/day) are under investigation for a potential role in Parkinson's disease treatment, but statistically significant benefits have not yet been demonstrated.19
A nutrition consultation would be appropriate to assist the patient in restricting protein prior to the evening hours, and restricting foods rich in vitamin B6.
What to Tell the Family
To minimize deconditioning, patients should maintain an active lifestyle to the extent possible. Also, patients should be aware that Parkinson's disease often causes weight loss. Family members can help reduce severe weight loss risk by providing breakfast, lunch, and between-meal snacks that are high in calories from whole grains (100% whole oats, oat bran, bulgur, barley, brown rice), fruits, 100% fruit juices, and vegetables. The family should ensure proper nutrient intake and be advised that protein deficiency is unlikely if adequate calories are consumed. Family members can improve the effectiveness of L-dopa therapy by reserving high-protein foods for evening meals. A qualified nutrition professional (eg, registered dietitian) may be helpful in accomplishing these aims.
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