Benserazide

Abstract/Resume

Parkinson's Disease (PD) is a chronic, progressive, neurode-- generative disease. People with PD are particularly susceptible to weight loss and malnutrition. Involuntary movements associated with PD result in increased energy expenditure, while both dis-- ease symptoms and medication side-effects can limit food intake. In addition, patients with the disease may choose to follow unconventional nutritional therapies that exacerbate malnutri-- tion. Dietitians play a key role in helping patients with PD to optimize their nutritional status and manage various nutrition-- related symptoms and medication side-effects. To assume this role, dietitians need to have current knowledge about PD and its nutritional consequences, as well as strategies for managing a variety of nutrition-related symptoms.

(Can J Diet Prac Res 2002; 63:81-87)

La maladie de Parkinson est une maladie chronique, progressive et neurodegenerative. Les personnel qui en sont atteintes sont particulierement sujettes a la perte de poids et a la malnutrition. Les mouvements involontaires associes a cette maladie entrainent une depense d'energie accrue, tandis que tant les symptomes que les effets secondaires des medicaments peuvent limiter l'apport alimentaire. De plus, les patients peuvent suivre des traitements nutritionnels non traditionnels qui accentuent la malnutrition. Les dietetistes jouent un role cle pour les aider a optimiser leur etat nutritionnel et a traiter divers symptomes lies a la nutrition et aux effets secondaires des medicaments. Pour assumer ce role, les dietetistes doivent connaitre la maladie de Parkinson et ses consequences nutritionnelles, de meme que les strategies de traite-- ment des symptomes lies a la nutrition.

(Rev can prat rech dieter 2002; 63:81-87)

INTRODUCTION

Parkinson's disease (PD) is a chronic, progressive neu-- rodegenerative disorder affecting approximately 80,000 Cana-- dians (Parkinson Society Canada). Many of its symptoms and treatment side effects have nutritional implications. This paper provides an overview of PD, including its treatment and its implications for nutritional care.

PARKINSON'S DISEASE OVERVIEW

The cardinal signs of PD - tremor, muscular rigidity, bradykinesia, and postural instability (Table 1) - result from dopamine depletion in the brain. Dopamine is a neurotransmit-- ter that allows messages to be sent from the brain to muscle to initiate voluntary movement (1). As PD progresses, a variety of other symptoms emerge, including dysphagia, soft monotone speech, impaired gastrointestinal motility, fatigue, depression, and cognitive impairment. PD is most prevalent in older indi-- viduals; 1:1,000 of those over age 55 and 1:100 of those over age 65 (2). The prevalence of PD is increasing at a faster rate than can be explained by the aging population (3). About 20% of cases are diagnosed in individuals under age 50 (4). Patients may live with this illness for up to 30 years (5,6). In the earlier stages of PD, patients continue to live independent lives (5). At the end stage, often lasting over ten years, patients typi-- cally become totally dependent, and develop nutrition-- related problems including malnutrition, dehydration, dysphagia and bowel dysfunction (5,7-9).

The cause of most cases of PD is unknown and there is evidence that PD is not one disease (10). People with fre-- quent exposure to large groups of people appear to be at increased risk for developing PD (11). For some patients, genetic or familial factors may be involved (12-15). Some antipsychotic and antiemetic medications cause parkinsonism, which is reversible if the drug can be discontinued (5,7,16).

Drug therapy is essential for controlling symptoms and maintaining mobility in PD (5,7,16). Drug therapy involves replacing or mimicking dopamine in the brain. The precur-- sor, levodopa, is used, as dopamine does not cross the blood-brain barrier. Levodopa is taken in combination with a dopa decarboxylase inhibitor (DDCI), carbidopa or benserazide, (e.g., Sinemet(R), Sinemet CR(R), and Prolopa(R)). DDCIs limit conversion of levodopa to dopamine in peripheral tissues, which allows a greater proportion of the levodopa to enter the brain and minimizes its adverse side effects.

Dopamine agonists (drugs mimick-- ing dopamine) are now often the first drug prescribed, particularly in patients who are young at the onset of PD (17). They are also regularly used in conjunction with levodopa therapy. Additional medications may be used as adjunctive therapy (1,5,16). Surgical treatments for PD include thalamo-- tomy to relieve tremor (18), and palli-- dotomy and deep brain stimulation (DBS), to relieve dyskinesias (involun-- tary movements) (19-22). Thalamo-- tomy and pallidotomy create permanent lesions in the basal ganglia. DBS employs a modified cardiac pacemaker and a probe to create a non-permanent lesion that can be turned on and off as needed. DBS is often used in patients who have already had one pallidotomy (19). Bilat-- eral stimulation of the subthalamic nucleus is being studied in several centres including Canada (19).

NUTRITIONAL CARE FOR PATIENTS WITH PD

Good nutrition is essential at all stages of PD (6,23,24). Nutritional needs are individual and vary according to disease stage, response to treatment, side effects of medications, and comor-- bid conditions. Patients with PD are at increased risk for malnutrition and weight loss (24-26), resulting from many factors including medication side effects (nausea and vomiting), dysphagia, dyskinesias, depression, dementia, reduced intake, self-imposed dietary restrictions, and increased time required to complete a meal (6,8,25,26). The likelihood of weight loss increases with disease progression (26). Body weight and indicators of nutrition risk must be routinely monitored (26).

There is no single, specific diet for PD. Patients with PD need a well-- balanced diet containing adequate energy and protein intake to prevent weight loss and muscle wasting, sufficient quantities of fibre and fluid to prevent constipation, and enough calcium to maintain existing bone struc-- ture (6,23,24,26). In practical terms, many of these recommendations may be difficult for patients to achieve, particularly in late-stage disease.

Patients with PD, like others with chronic progressive conditions, may be attracted to unconventional diets that could further compromise nutri-- tional status (27). While dietitians need to respect the right of patients to explore alternative therapies, they have a role in informing patients about known risks and benefits of such therapies, and cautioning against those that may cause harm.

Energy requirements

Energy requirements vary by dis-- ease stage and severity of symptoms (24). Patients with dyskinesias may expend as much energy as people undertaking moderate physical activ-- ity, so energy intake should be esti-- mated accordingly (24). Increased energy expenditure is likely a factor in the weight loss observed in late-- stage disease (24).

Although weight loss is a much more prevalent concern than over-- weight in PD, some individuals with PD may be overweight in the earlier stages of the disease, which can further hamper their mobility. Stringent diets are not recommended, because they can contribute to diminished energy level and are often unsuccessful in the long term. Patients who are overweight should be encouraged to stabilize their weight by eating nutritious foods, con-- trolling portions, and being as active as their symptoms allow.

Protein

Amino acids compete with levodopa for transport across the blood-- brain barrier (24). In the late 1980s, it was postulated that low protein diets might improve medication uptake and enhance mobility in patients taking levodopa who had severe medication-- induced fluctuations in mobility (28). While dietary protein restriction seemed to be helpful for a small number of patients taking immediate-release levodopa (in controlled study settings), the protein-restricted diet was considered to be unhealthy for contin-- uous use, particularly in a patient pop-- ulation prone to malnutrition (29,30). With the introduction of controlled release preparations of levodopa, the earlier use of combined lower dose therapy, and use of surgical interven-- tions, the proportion of individuals with PD who might benefit from pro-- tein restriction has declined (24,30,31). As well, long-term use of restrictive diets is likely to increase propensity for other nutrition-related conditions, such as osteoporosis (32). However, the myth persists and dietitians and nurses continue to encounter patients with PD on severely restricted, low protein diets.

A very small number of patients may notice that eating high protein meals affects the absorption of their drugs. Rather than restricting protein, these patients should be advised to redistribute their protein throughout the day, avoid large amounts of pro-- tein at one time, and avoid taking high protein foods in conjunction with their levodopa doses (7,31). These patients need to be made aware that adequate protein intake is necessary to maintain optimal health.

Despite professional concerns about the use of protein-restricted diets in this population, some patients may have heard about the low protein diet and insist on trying it. These patients should be monitored by a neurologist, as levodopa side effects, including nau-- sea, dyskinesias and hallucinations may emerge, requiring medication adjust-- ment (25). These patients should con-- sult with a dietitian, who can advise them about optimizing the nutritional content of the diet (25). Patients should be informed that they will note benefits of the protein restriction almost imme-- diately. If no benefits are seen after one or two weeks, the diet should be discontinued (29).

Vitamins and minerals

Patients with PD who have diffi-- culty maintaining a balanced diet may benefit from taking a multivitamin-- mineral preparation (24-26). It has been postulated that antioxidant therapy could delay progression of PD by minimising oxidative stress associated with the death of dopamine neurons; however, this theory is highly contro-- versial (33). The results of a large, multicentre study of high dose alpha-- tocopherol therapy in PD were incon-- clusive (34) and there are concerns that the vitamin E might not even have crossed the blood-brain barrier (35). In light of this, general guidelines for supplementation should be used (24,25). Those patients opting to use high dose vitamin supplements should be informed about potential side effects (36).

Pyridoxine (vitamin B6)

In the past, pyridoxine restriction was recommended for patients using levodopa, as pyridoxine facilitates the conversion of levodopa to dopamine outside the brain. Now that combined levodopa/DDCI preparations are routinely used, pyridoxine intake need not be restricted (24,36).

Calcium/vitamin D

Patients with PD are prone to osteoporosis. Bone mass density of patients with PD closely correlates with disease severity (37). Immobility and the resulting lack of weight-- bearing exercise, decreased intake, and poor nutritional status are contributing factors (37). Calcium and vitamin D intake need to be assessed in the early stages of the disease to prevent or limit osteoporosis (24, 37). Patients with PD who are at risk for osteoporosis should consult their physi-- clans about all available diagnostic and treatment options for osteoporosis, including bone density scanning, hormone replacement therapy and medications.

People with PD should be advised to take 1,000-1,500 mg of calcium and 10-15 pg vitamin D daily (24), a recom-- mendation consistent with current Dietary Reference Intakes (38). Those who have poor overall intake or who avoid dairy products are likely to require supplementa-- tion with calcium and vitamin D to meet these recommendations. Although concerns have been raised about whether supplements can assist in maintaining bone density in immobile patients with PD (37), clinical trials involving calcium and vitamin D supplementation in an elderly population offer compelling evidence for the benefits of supplementation (39, 40).

Herbal supplements

With the current popularity of herbal supplements, patients with PD are likely to use them. Little is known about the pos-- sible interaction between herbal supplements and PD symp-- toms and/or medications, although some reports have been published about general interactions (41,42). Patients with PD should be advised to exercise caution when using herbal supplements and to discontinue them if side-effects occur.

MEDICATION SIDE EFFECTS

Some of the nutritional problems encountered by PD patients are due to medication side-effects. Dietitians work-- ing with these patients need to be aware of antiparkinson medications and strategies for managing their nutrition-- related side effects (Table 2). Most side effects occur with initiation of treatment and abate as tolerance develops (1,5,6,16,41,43).

SYMPTOMS AND THEIR MANAGEMENT

Bowel dysfunction

Constipation is a serious problem, because patients with PD are particularly susceptible to impaction, obstruction, volvulus, and paralytic ileus. If these are left untreated, they can result in death (5,7,9,44). Contributing factors include slowed gastric motility, autonomic dysfunction, medication side effects, and the inability to exercise, eat enough fibre, or drink enough fluid (5,9,31,45,46). Management consists of dietary changes, exercise, and pharmacotherapy (5,9,45,46). Dietary modifications for constipation are aimed at increas-- ing bulk and softening stool (9,25). Fibre intake should be increased gradually, and diets high in fibre should be advocated only if patients can achieve adequate fluid intake (at least 1.5-2 L per day). Patients may have difficulty doing this if they have not been regular water drinkers, are too weak to drink, avoid drinking to prevent having to mobilise to go to the bathroom, or are unable to take liquids due to dysphagia (31). In addition to undertaking dietary measures, patients should be encouraged to increase physical activity within the boundaries of their physical capabilities (23).

If constipation persists despite dietary modification and increased physical activity, a stool softener given with meals can be helpful. If necessary, this can be followed by a prokinetic agent to increase intestinal motility (9). Patients who do not respond to other interventions may have to use other mild laxatives, suppositories and enemas and their use may become inevitable in the later stages of the disease (9). Some patients have difficulty passing normal, soft stools due to impaired anorectal muscle coordination or fatigue, which interfere with the ability to expel faeces (9,47). Dietary modifications are unhelpful in this situa-- tion; patients can try applying warm water and/or gentle finger stimulation (9). If these measures fail, patients may need to use a glycerine suppository (9).

Dysphagia

Dysphagia resulting from bradykinesia and rigidity occurs in over 50% of individuals with PD (48-50), and is most prevalent in late-stage disease (50). Dysphagia-related aspiration is a common cause of death in PD (7,48). Dys-- phagia varies in severity and can affect the mouth, pharynx, and esophagus (48,49). Patients with PD also experience saliva build-up in the mouth, leading to drooling, resulting from the inability to swallow voluntarily, and stooped pos-- ture. This may be embarrassing for patients. Mouth care before meals can minimise the impact on enjoyment of food. Pilot studies indicate that injections of botulinum toxin may be effective in reducing saliva build-up (51,52).

A swallowing assessment by a trained therapist is recom-- mended to evaluate swallowing dysfunction and make diet, positioning, and swallowing technique recommendations (25,53-55). Modifications in diet texture, fluid viscosity, and food temperature may be required. Patients who have diffi-- culty moving their jaws, lips, or tongue may find soft, minced or pureed foods and thick soups easiest to eat. Those who have difficulty swallowing thin liquids may find more vis-- cous fluids and carbonated beverages easier to swallow (31). Foods that are ice-cold may help to stimulate swallowing (56). Sour boluses enhance both oral and pharyngeal aspects of swallowing (57).

Choking is common in patients with dysphagia. To reduce this risk, patients should eat in an upright position and care-- givers should learn the Heimlich maneuver. Patients with severe dysphagia, particularly those who have had choking episodes, may need to be considered for gastrostomy feeding, which can also be used to administer drugs (5,25,58). All antiparkinson drugs, with the exception of controlled release preparations, can be crushed and administered through a feeding tube (5). Ethical and quality of life issues should be considered before gastrostomy feeding is implemented.

Nausea/vomiting/anorexia

The anorexia, nausea, and vomiting associated with antiparkinson drugs most often occurs with their initiation; the symptoms subside as medication tolerance develops (5,6,16,24). Some physicians advise patients to take their antiparkinson drugs on an empty stomach; however, taking these drugs with a meal or snack (such as juice or ginger ale plus crackers, cookies, or fruit) can help to minimize nausea (6). In addition, there are prokinetic reasons why controlled-- release levodopa preparations should be taken with food (36). If nausea persists despite taking medications with food, tak-- ing domperidone (Motilium) 30-60 minutes before each dose of drug can be effective. Domperidone prevents levodopa from passing through the vomiting centre (6,7,43). The patient with nausea and anorexia is at risk for inadequate nutrition and weight loss, and should be monitored.

Delayed gastric emptying

Delayed gastric emptying occurs frequently in PD (59), likely caused by autonomic dysfunction and chronic medica-- tion administration (24,25). Delayed gastric emptying can cause early satiety, decreased appetite, nausea, vomiting, abdominal bloating, heartburn and reflux, and can contribute to decreased drug absorption.

Strategies that may help with delayed gastric emptying include eating small, frequent meals and snacks, and taking medications 15-30 minutes before meals. The latter may be difficult for those patients who suffer nausea from their med-- ication (24,25). A prokinetic agent, such as domperidone, may be required to improve gastric motility. (9,24,45,60). Domperidone has the added benefit of preventing reflux. Although a diet lower in protein and fat empties the stom-- ach more quickly (24,45,60,61), this diet is not advisable for PD patients, as they are at risk for malnutrition.

Orthostatic hypotension

Patients with PD often develop orthostatic hypotension (OH), a fall in blood pressure that occurs upon standing. It may be symptomatic (dizziness, fainting) or asymptomatic (62). Contributing factors in PD include duration of disease, use of antiparkinson drugs, and decreased fluid intake. Patients with OH should be advised to increase their dietary sodium. Practical methods for increasing sodium are liberal use of table salt and high salt foods or administration of sodium tablets (5,62-64). For patients on tube feeding, salt can be added to the tube feed, or a saline flush can be used. PD patients with OH should increase their fluid intake to 1.5-2L per day if possible (5). Drugs such as fludrocortisone or amatine may be required to increase intravascular volume (5,25,63).

Bradykinesia

The slowness and stiffness associated with PD can make eating laborious and may adversely affect food intake. Small portions on a small plate that can be regularly replenished are more appetizing than large plates of food. Food can be cut in advance in both home and restaurant kitchens to reduce self-consciousness in the presence of others. Some patients may opt to eat quietly at home before large family or public outings, thus reducing their need to focus on eat-- ing when they are also trying to enjoy themselves (23,65).

Dyskinesias

Dyskinesias may impair feeding, and can increase energy requirements (24). High-energy foods, nutrition supple-- ments and increased time to eat are often required. Finger foods may help individuals to be independent with feeding (23), and dyskinetic patients may also prefer to eat in the privacy of their own homes (65).

Depression

Depression occurs in up to 40% of patients with PD (65-67), and contributes to malnutrition risk (24,66,67). Patients who appear depressed should be encouraged to see their physician. Antidepressant therapy is frequently necessary and beneficial (10,67), and some antidepressants such as tricyclics stimulate appetite and cause weight gain (36,65,67).

Impaired cognitive function

Dementia occurs in approximately 30% of patients with PD; drug-induced psychosis may also occur in late-stage patients when the amount of drug needed to maintain mobil-- ity is high enough to induce psychiatric side effects (5,7). Patients with impaired cognitive function are at increased risk for malnutrition due to their impaired ability to prepare and consume food (24,25,68). Psychotic patients may have paranoid delusions about their food, leading to reduced intake (24,25,68). Patients with cognitive impairment may benefit from a meal delivery program and/or use of nutri-- tion supplements (24,25,68). Patients with drug-induced psychosis may need a reduction in PD medication or the addition of one of the newer antipsychotic agents (clozapine, olanzapine or quietapine) (8,69,70).

RELEVANCE TO PRACTICE

Dietitians can help PD patients to optimize their nutri-- tional status and manage nutrition-related symptoms at all stages of the disease. To assume this role, they need to have current knowledge about PD and its nutritional consequences. To develop practical strategies for managing the myriad of nutrition-related symptoms arising in PD, it may be nec-- essary for dietitians to seek the advice of colleagues with expertise in a variety of specialty areas including neurology, geriatrics, dysphagia, gastrointestinal disorders, and nutri-- tion support.

Acknowledgments

This work received no financial support from any outside agency or company. Susan Calne's work is supported by the National Parkinson Foundation Miami through a Centre of Excellence Grant.

References

1. Lang AE, Lozano AM. Parkinson's disease: second of two parts. N Engl J Med 1998;339(16):1130-1143.

2. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967;17:427-442.

3. Lilienfeld DE, Perl DP. Mortality from parkinsonism in the United States, 1990-2040. Neurodegeneration 1994;3:21-24.

4. Schrag A, Ben-Schlomo Y, Brown R, et al. Young-onset Parkinson's disease revisited - clinical features, natural history and mortality. Mov Disord 1998;13 (6):885-894.

5. Caine DB, Caine S. Treatment of Parkinson's disease. In: Ancil RJ, Holliday SG, Mithani AH, eds. Therapeutics in Geriatric Neuropsychiatry. Chichester: John Wiley & Sons Ltd; 1997.p. 1-12.

6. Caine S. Nursing care of patients with idiopathic parkinsonism. Nursing Times 1994; 90:38-39.

7. Caine DB. Treatment of Parkinson's disease. N Engl J Med 1993;329:1021-1027.

8. Korczyn A. Neuropsychiatric manifestations of Parkinson's disease. In: Caine DB, Caine SM, eds. Parkinson's disease: advances in neurology Vol 86. Philadelphia: Lippincott,Williams and Wilkins; 2001.p. 395-398.

9. Pfeiffer RF, Quigley EMM. Gastrointestinal motility problems in patients with Parkinson's disease - Epidemiology, pathophysiology and guidelines for management. Central Nervous System Drugs

1999;11 (6):435-448.

10. Caine DB. Parkinson's disease is not one disease. Parkinsonism & Related Disorders 2001;7(1):3-7.

11. Tsui JKC, Caine DB, Wang Y, et al. Occupational risk factors in Parkinson's disease. Can J Public Health 1999;90(5):334-335.

12. Caine S, Schoenberg B, Martin W, et al. Familial Parkinson's disease: possible role of environmental factors. Can J Neurol Sci 1987;14:303-305. 13. Hattori N, Kitada T, Matsumine H, et al. Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann Neurol 1998;44(6):935-941.

14. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the a-Synuclein gene identified in families with Parkinson's disease. Science 1997;276:2045-2047.

15. Tanner CM, Ottman R, Goldman SM, et al. Parkinson disease in twins: an etiologic study. JAMA 1999;281 (4):341-346.

16. Uitti R, Wszolek Z. Medical treatment of Parkinson's disease. Neuroscience News 1999;2:36-43.

17. Rascol OFJJ, Thalamas CGM, Montastruc J-L Dopamine agonists: their role in the nanagement of Parkinson's disease. In: Calne DB, Calne SM, ed. Parkinson's disease, Advances in Neurology. Philadelphia: Lippincott, Williams and Wilkins; 2001.p. 301-309.

18. Narabayashi H. Stereotactic surgery and Parkinson's disease. Funct Neurol 1988;70:114-121.

19. Benabid A, Koudsie A, Benazzouz A, et al. Deep brain stimulation for Parkinson's disease. In: Calne DB, Calne SM, ed. Parkinson's disease, advances in neurology. Philadelphia: Lippincott, Williams and Wilkins; 2001.p. 405-412.

20. Laitinen LV. Ventroposterolateral pallidotomy. Stereotact Funct Neurosurg 1994;62:41-52.

21. Samii A, Turnbull IM, Kishore A, et al. Reassessment of unilateral pallidotomy in Parkinson's disease. A 2-year follow-up study. Brain 1999;122:417-425.

22. Pal PK, Samii A, Kishore A, et al. Long-term outcome of unilateral pallidotomy: follow up of 15 patients for three years.

J Neurol Neurosurg Psychiatry 2000;69(3):337-344.

23. Caine S, McConnell B, Shaw C, et al. Taking charge: A guide to living with parkinsonism. 3rd ed. Toronto: Parkinson Foundation of Canada; 1999.

24. Carter J, Nutt J. Dietary issues in Parkinson's disease. In: Koller W, Paulson G, eds. Therapy of Parkinson's disease. New York: Marcel Dekker, 1995:443-461.

25. Olanow CW, Koller W. An algorithm (decision tree) for the management of Parkinson's disease: treatment guidelines. Neurology 1998;50(Supp 3):Sl-557.

26. Beyer P, Palarimo M, Michalek D, et al. Weight change and body composition in patients with Parkinson's disease. J Am Diet Assoc 1995;95 (9):979-983.

27. Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson's disease. Ann Rev Neurosci 1999;22:123-144.

28. Pincus JH, Barry KM. Plasma levels of amino acids correlate with motor fluctuations in parkinsonism. Arch Neurol 1987;44(10):1006-1009.

29. Pare S, Barr S, Ross S. Effect of daytime protein restriction on nutrient intakes of free-living Parkinson's disease patients. Am J Clin Nutr 1992;55:701-707.

30. Tsui JKC, Ross S, Poulin K, et al. The effect of dietary protein on the efficacy of L-dopa: A double blind study. Neurology 1989;39:4:549-552. 31. Caine SM, Kumar A. Management of late stage Parkinson's Disease.

Parkinsonism and Related Disorders 2003. In press.

32. Chiu JF, Lan SJ, Yang CY, et al. Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women. Calcif Tissue Int 1997;60(3):245-249.

33. Calne DB. The free radical hypothesis in idiopathic parkinsonism: Evidence against it. Ann of Neurol 1992;32:799-803.

34. The Parkinson Study Group. Impact of deprenyl and tocopherol treatment in Parkinson's disease in DATATOP subjects not requiring levodopa. Ann Neurol 1996;39:29-36.

35. Chase T. National Institutes of Health. Personal communication, 1999 36. Compendium of Pharmaceuticals and Specialties (CPS). 33rd ed. Ottawa: Canadian Pharmacists Association;1998.

37. Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson's disease. Neurology 1997;49:1273-1277.

38. Institute of Medicine (U.S.), Standing committee on the scientific evaluation of dietary reference intakes. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press, 1997.

39. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;327(23):1637-1642.

40. Chapuy MC, Meunier PJ. Calcium and vitamin D3, a prevention of femoral neck fractures in elderly women. Presse Med

1993;22 (13):615-616.

41. McCarty MF, Russell AL, Seed MP. Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis. Medical Hypotheses 2000;54(5):798-802.

42. Moore LB, Goodwin B, Jones SA et al. St. John's Wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences of the United States of America 2000;97(13):7500-7502.

43. Soykan I, Saroseik I, Shifflett J, et al. Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. Mov Disord 1997;12(6):952-957.

44. Rosenthal MJ, Marshall CE. Sigmoid volvulus in association with parkinsonism. Report of four cases. J Am Geriatr Soc 1987;35(7):683-684.

45. Jost WH. Gastrointestinal motility problems in patients with Parkinson's disease. Effects of antiparkinsonian treatment and guidelines for management. Drugs Aging 1997;10(4):249-258.

46. Martignoni E, Pacchetti C, Godi L, et al. Autonomic disorders in Parkinson's disease. J Neural Transm 1995;Suppl. 45:11-19.

47. Ashraf W, Wszolek ZK, Pfeiffer RF, et al. Anorectal function in fluctuating (on-off) Parkinson's disease: evaluation by combined anorectal manometry and electromyography. Mov Disord 1995;10(5):650-657.

48. Johnston BT, Li Q, Castell JA, et al. Swallowing and esophageal function in Parkinson's disease. Am J Gastroenterol 1995;90(10):1741-1746.

49. Miller R, Groher M. General treatment of neurologic swallowing disorders. In: Groher ME, ed. Dysphagia: diagnosis and management. Boston: Butterworth Heineman; 1997.p. 223-241.

50. Pengilly KI Introduction to speech and swallowing problems associated with Parkinson's disease. Miami: National Parkinson Foundation; 1998. 51. Friedman A, Potulska A. Quantative assessment of parkinsonian

sialorrhea and results of treatment with botulinum toxin. Parkinsonism and Related Disorders 2001;7(4):329-332.

52. Pal PK, Came DB, Calne S, et al. Botulinum - A toxin in the treatment of sialorrhea in patients with Parkinson's disease. Neurology 2000;54:244-247. 53. Clarke CE, Gullaksen E, Macdonald S, et al. Referral criteria for speech

and language therapy assessment of dysphagia caused by idiopathic Parkinson's disease. Acta Neurol Stand 1998;97(1):27-35.

54. Nagaya M, Kachi T, Yamada T. Effect of swallowing training on swallowing disorders in Parkinson's disease. Scand J Rehabil Med 2000;32(1):11-15.

55. Nagaya M, Kachi T, Yamada T, et al. Videofluorographic study of swallowing in Parkinson's disease. Dysphagia 1998;13(2):95-100.

56. Farber SD. Neurorehabilitation: A multisensory approach. Philadelphia: Saunders; 1982.

57. Logemann JA, Pauloski BR, Colangelo L, et al. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38(3):556-563.

58. Fuh JL, Lee RC, Wang SJ, et al. Swallowing difficulty in Parkinson's disease. Clin Neurol & Neurosurg 1997;99(2):106-112.

59. Djaldetti R, Baron J, Ziv I, et al. Gastric emptying in Parkinson's disease: patients with and without response fluctuations. Neurology 1996;46(4):1051-1054.

60. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Clinical Neuroscience 1998;5(2):136-146.

61. Cunningham KM, Read NW. The effect of incorporating fat into different components of a meal on gastric emptying and postprandial blood glucose and insulin responses. Br J Nutr 1989;61 (2):285-290.

62. Onrot J. Therapeutic Choices. 2nd ed. Toronto: Canadian Association of Pharmacists; 1998.

63. Senard JM, Rai S, Lapeyre-Mestre Mea. Prevalence of orthostatic hypotension in Parkinson's disease. J Neurol Neurosurg Psychiat 1997;63:584-589.

64. Jansen R, Lipstiz L Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med 1995;122:286-295.

65. Caine S, Hurwitz T. Adjustment, adaptation, and accommodation: Psychosocial approaches to living with Parkinson's disease. Miami, Florida. National Parkinson Foundation, 1997.

66. Cummings JL. Depression and Parkinson's disease: a review. Am J Psychiatry 1992;149(4):443-454.

67. Oertel WH, Hoefinger G, Caraceni T, et al. Depression in Parkinson's disease: an update. In: Caine DB, Came SM, ed. Parkinson's disease Advances in Neurol 2001;86:373-383.

68. Lyons LI Schindell C. Dementia: the nurse's role. In: Ancil R, Holliday SG, eds. Therapeutics in geriatric psychiatry. Chichister: Wiley;

1997.p. 115-127.

69. Fernandez HH, Friedman JH, Jacques C, et al. Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease. Mov Disord 1999;14(3):484-487.

70. Wolters EC. Psychiatric complications in the treatment of Parkinson's disease. In: Caine DB, Caine S, ed. Parkinson's disease: Advances in Neurology. Philadelphia:Lippincott, Williams and Wilkins; 2001.p. 385-93.

MEREDITH L. CUSHING, RDN, formerly Vancouver Hospital and Health Sciences Centre, currently Indiana University Purdue University Indianapolis (IUPUI);

KAROL A. TRAVISS, MSc, RDN, Vancouver Hospital and Health Sciences Centre, Department of Food and Nutrition Services, Vancouver, BC; SUSAN M. CALNE, CN, RN, Pacific Parkinsons Research Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC

Copyright Dietitians of Canada Summer 2002
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