Body weight in patients with Parkinson's disease

Review

Body Weight in Patients With Parkinson’s Disease

Cornelius G. Bachmann, MD,1 and Claudia Trenkwalder, MD1,2*

1Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany2Paracelsus–Elena Klinik, Kassel, Germany

Abstract: There is some evidence suggesting that Parkinson’sdisease (PD) patients exhibit lower body weight when com-pared to age-matched healthy subjects. Low body mass index(BMI) is correlated with low bone mineral density, both ofwhich are major risk factors for hip fractures. Possible deter-minants of weight loss in PD patients include hyposmia, im-paired hand–mouth coordination, difficulty chewing, dyspha-gia, intestinal hypomotility, depression, decreased rewardprocessing of dopaminergic mesolimbic regions, nausea, andanorexia as the side effects of medication, and increased energyrequirements due to muscular rigidity and involuntary move-ments. It is unclear whether PD patients in general, or only asubgroup of those affected, definitely show lower BMI in the

advanced stages of the disease. We therefore recommend thatthe body weight of PD patients be monitored monthly as thedisease progresses, and that a patient’s nutrition should besupplemented with sufficient amounts of vitamin D and cal-cium to reduce the risk of hip fractures and strengthen bonedensity. Because mealtimes may coincide with unpredictableoff periods associated with akinesia and impaired hand–mouthcoordination, PD patients also need flexible food schedules thataccommodate the associated symptoms of this disease. © 2006Movement Disorder Society

Key words: Parkinson’s disease; nutrition; body mass in-dex; dyskinesia

Several studies have concordantly shown that patientswith Parkinson’s disease (PD) have lower body weightsin comparison with age-matched subjects.1–3 Their lowerbody weight may affect patients’ overall functional abil-ity and their daily activities. In view of the increased riskof falling, reduced body mass makes parkinsonian pa-tients prone to bone fractures,4 especially hip fractures,5,6

and subsequent risks such as pneumonia and pressureulcers.7–9 Consequently, it is important that the majordeterminants in the pathophysiology of weight loss in PDpatients be clarified. Studying the longitudinal weightchanges of 468 patients with Parkinson’s disease, Chenand colleagues3 observed a mean body weight loss of 5.2

pounds during the 10 years preceding the diagnosis, butwith a fairly constant weight 2 to 4 years before thediagnosis, and a mean loss of 7.7 pounds during the 8years following the diagnosis. The findings of Chen andcolleagues3 support earlier results suggesting a signifi-cant correlation of weight loss with the stage of Parkin-son’s disease.2

A variety of components (for overview, see Table 1)may contribute to weight loss, involving hyposmia,10

insufficient food ingestion, impaired hand–mouth coor-dination and difficulty chewing, dysphagia,11 intestinalhypomotility,12 depression,13 decreased reward process-ing of dopaminergic mesolimbic regions,14 nausea andanorexia as side effects of dopaminergic medication, andincreased energy requirements due to muscular rigidityand increased involuntary movements such as dyskinesiaand tremor.15,16 In contrast, weight gain is often observedin PD patients after pallidotomy17–19 and stimulation ofthe subthalamic nucleus.20,21 A number of investigations

*Correspondence to: Dr. Claudia Trenkwalder, Paracelsus-ElenaKlinik, Klinikstrasse 16, D-34128 Kassel, Germany.E-mail: [email protected]

Received 23 January 2006; Accepted 19 April 2006Published online 6 September 2006 in Wiley InterScience (www.

interscience.wiley.com). DOI: 10.1002/mds.21068

Movement DisordersVol. 21, No. 11, 2006, pp. 1824–1830© 2006 Movement Disorder Society

1824

TABLE 1. Study data

Study Study design Number of patients Results/conclusion

Energy intakeChen et al.3 Longitudinal (1986-2000; 1976-1998)

measurements and statistic analysis ofbody weight and energy intake

468 PD patients (267male; 201 female),age-matchedcontrols without PD

Weight loss in PD patients not aresult of decreased energy intake

Motor symptoms and energyexpenditureMacia et al.21 Weight, energy expenditure/intake, and motor

symptoms (UPDRS) were studied in PDpatients after STN DBS vs. nonoperatedPD patients

19 PD patients afterSTN DBS vs. 14nonoperated PDpatients

Mean weight gain of 9.7 � 7 kg afterSTN DBS; correlation ofpostoperative changes of restingenergy expenditure and UPDRS IIIscore

Ondo et al.17 Body weight, UPDRS, Beck DepressionInventory before and during 1-year follow-up after unilateral pallidotomy

60 PD patients beforeand within 1 yearafter pallidotomy; 9patients dropped out

Mean weight gain of 4.0 � 4.1 kgwithin 1 year; no correlation ofpostoperative changes in dyskinesiaratings, mood, food intake,dysphagia with weight gain

Markus and colleagues16 Statistical analysis of BMI andanthropometric indexes (triceps and bicepsskinfold thickness, arm musclecircumference; four grades oftremor/dyskinesia severity; freezing)

95 PD patients (53male; 42 female); 8equally disabledpatients withchronic upper motorneuron lesions ascontrol group

BMI lower in PD patients; presenceof dyskinesias correlated moststrongly to undernutrition

DysphagiaMuller et al.11 Retrospective postmortem analysis of the

development of dysphagia in 83pathologically confirmed parkinsoniansyndromes

PD: n � 17; MSA: n� 15; DLB: n �14; CBD: n � 13;PSP: n � 24

Dysphagia within 1 year of disease inatypical parkinsonian syndromes;mean latencies: PD, 130 months;PSP, 42 months; DLB, 43 months;CBD, 64 months; MSA, 67 months

HyposmiaWenning et al.64 Olfactory function assessed with UPSIT PD: n � 118; MSA: n

� 29; PSP: n � 15;CBD: n � 7;healthy: n � 123

Marked impairment in PD; mildimpairment in MSA; normalolfaction in PSP and CBD

Ondo et al.17 UPSIT, Weight, UPDRS, Beck DepressionInventory before and during 1-year follow-up after unilateral pallidotomy

Subset out of 60 PDpatients before andwithin 1 year afterpallidotomy

No significant changes in olfactionpostoperatively

OrexinDrouot et al.35 Orexin-A/hypocretin-1 ventricular CSF levels

of advanced PD patients19 PD patients (7

female; 12 male) vs.5 control subjects

Low ventricular CSF levels inadvanced PD; orexin levelcorrelated with disease severity, notwith disease duration;dopaminergic medication dose

LeptinEvidente et al.36 Serum leptin levels, BMI, satiety ratings in

PD patients with and without weight loss18 PD patients with

unintended weightloss; 18 PD patientswith stable weight

Unintended weight loss is unlikelydue to abnormal serum leptin levels

GHHanew and Utsumi40 Measurement of plasma GH after subsequent

application of GHRH, GHRH-antagonist,and levodopa

10 healthy men (age:20-33 years; meanBMI: 21.2 � 0.4)

Levodopa evokes GH release viasecretion of hypothalamic GHRH

Reduced mesocorticolimbicprocessingKunig et al.14 Analysis of regional cerebral blood flow with

H2150 PET during prelearned pattern

recognition tasks with delayed response inPD patients and controls

12 PD patients (9male; 3 female) and13 age-matchedcontrol subjects

Extended activation oftemporoparietal association cortexand primary motor cortex in PDpatients, suggesting compensatorycortical loops

GHRH, growth hormone-releasing hormone; UPDRS, Unified Parkinson’s Disease Rating Scale; UPSIT, University of Pennsylvania SmellIdentification Test.

BODY WEIGHT 1825

Movement Disorders, Vol. 21, No. 11, 2006

following neurosurgery did not demonstrate any signif-icant correlation between postoperative amelioration ofdyskinesias with weight gain, suggesting that dyskinesiais unlikely to be a major cause of weight loss inPD.17,19,21 Weight loss in Parkinson’s disease may bemultifactorial and further research must be conducted tounderstand fully the mechanisms involved.

POSSIBLE DETERMINANTS OF WEIGHTLOSS IN PARKINSON’S DISEASE

Body composition evaluation in PD patients by Beyerand colleagues2 and Markus and colleagues16 revealedthat weight loss in PD patients occurs predominantlybecause of fat loss rather than loss of muscle tissue.Since disparity between energy intake and energy expen-diture is recognized as the essential cause of weight loss,energy expenditure in PD patients has been systemati-cally studied. A longitudinal cohort study by Chen andcolleagues3 observed increased energy intake in PD pa-tients. This observation, however, was based on foodfrequency questionnaires rather than calorimetrical mea-surements. Levi and colleagues22 and Markus and col-leagues15,16 applied indirect calorimetry with the venti-lated hood technique and consistently reportedsignificantly increased resting energy expenditure in un-treated and even optimally treated PD patients comparedto age-matched healthy subjects or to equally immobileneurological patients with chronic upper motor neurondisease.16 The significance of these studies regardingenergy expenditure in PD patients may be limited, asresting energy accounts for only 60% to 80% of dailyenergy expenditure. Levi and colleagues22 and Markusand colleagues15,16 applied the ventilated hood techniqueonly at defined daily intervals, while Toth and col-leagues23 continuously assessed daily energy expenditureover 10 days. A combination of double-labeled watertechnique and resting indirect calorimetry was used.Resting energy expenditure did not vary significantlybetween PD patients and controls. The same study founda lower daily energy expenditure (consisting of restingand physical activity energy expenditure) in PD patientsdue to impaired physical activity compared to healthycontrols. Therefore, Toth and colleagues23 assumed thatdecreased energy intake might be a determinant ofweight loss in PD patients, rather than increased energyexpenditure, as had been hypothesized.15,16,23

BODY WEIGHT CHANGES AND MOTORSYMPTOMS

The current literature does not answer the question ofwhether dyskinesia itself leads to weight loss due toenergy expenditure.15,23,24 Studying the relation of body

weight and dyskinesias, Arabia and colleagues24 sug-gested that during long-term treatment, lighter PD pa-tients are more likely to be given a higher cumulativedose of levodopa and thus are more prone to levodopa-induced dyskinesias. They determined that dyskinesiasare a consequence of altered levodopa pharmacokineticsdue to low body weight. Follow-up investigations onweight gain after unilateral pallidotomy and two fol-low-up studies after bilateral subthalamic nucleus (STN)stimulation [STN deep brain stimulation (DBS)] in Par-kinson’s disease patients contradict the assumption thatdyskinesias are the most significant determinant ofweight loss. Eighteen patients in a study by Vitek andcolleagues,19 17 with dyskinesias, reported a meanweight increase of 5 kg during a 6-month follow-up afterunilateral pallidotomy. After surgery, dyskinesia wasabsent in 12 of 17 patients, but there was no correlationof body weight gain and improvement in dyskinesiascales.

Similarly, Ondo and colleagues17 detected an averageweight gain of 4.0 � 4.1 kg in 49 of 60 patients 1 yearafter unilateral pallidotomy and saw no correlation be-tween changes of “percent time with dyskinesia” andweight gain. The same study demonstrated a correlationbetween motor scores during off periods, especially gaitand tremor improvements and weight gain. A third fol-low-up study by Lang and colleagues25 reported a meanweight gain of 13.6 kg in 14 of 40 patients within 1 yearafter unilateral pallidotomy, but weight gain was relatedto reduced dyskinesia (assessed by a self-rating scale) inonly 6 of 14 patients. STN DBS resulted in increasedappetite and an average weight gain of 13% within16.3 � 7.6 months in all seven patients with advancedPD. There was no correlation between weight gain andchanges in postsurgery dyskinesia scores.26 Unfortu-nately, Moro and colleagues26 did not provide detailedinformation on how they assessed appetite.

There exist a variety of measurable physical parame-ters providing information on body composition. One ofthe widely accepted parameters is skinfold thickness. Inan analysis of anthropometric parameters in PD patients,Markus and colleagues16 correlated a reduced skinfoldthickness (related to percentage body fat) with weightloss. They concluded that dyskinesia is the clinical symp-tom most closely associated with weight loss. A fol-low-up report conducted 1 year after STN DBS showeda marked body weight increase in 29 of 30 patients.20

Dyskinesia score assessments are not recorded in thepublication. No correlation between body weight gainand reduced levodopa dosage could be observed. Maciaand colleagues21 recently reported a significant weightincrease related to decreased resting energy expenditure

1826 C.G. BACHMANN AND C. TRENKWALDER


after STN DBS in 19 PD patients as compared to 14 PDpatients who did not receive STN DBS. Macia andcolleagues21 hypothesized that decreased administrationof dopaminergic medication and improvement in dyski-nesias could be crucial for the observed weight gain afterSTN DBS, as long-term dopaminergic therapy mightincrease lipolysis as a consequence of hyperinsulinaemiaand increased growth hormone (GH) secretion and even-tually result in weight loss.27

HYPOSMIA

Hyposmia could also be one of the components con-tributing to weight loss in patients with PD. A significantloss in olfactory-evoked potentials and subjective smelltesting in patients with Parkinson’s disease has beendemonstrated. Ondo and colleagues17 tested olfaction ina “small subset” (no numbers given) of 60 patients pre-and postpallidotomy using the University of Pennsylva-nia Smell Identification Test. None of the patientsshowed any improvement, suggesting that increased sen-sitivity to smell and taste is unlikely to be the cause of theobserved body weight changes in postpallidotomypatients.

DYSPHAGIA

A retrospective study by Muller and colleagues11

showed that dysphagia occurs later in the course of PDcompared to atypical parkinsonian syndromes, such asprogressive supranuclear palsy (PSP), multiple-systematrophy (MSA), corticobasal degeneration (CBD), anddementia with Lewy bodies (DLB). Although diffi-culty swallowing solid food due to oropharyngeal dys-function may increase weight loss in advanced Par-kinson’s disease, where it may play a significant role,it is unlikely to be the major determinant of earlyweight loss.11 It may be hypothesized that dysphagiaand impaired hand–mouth coordination that occur dur-ing akinetic off states could be an important etiologicalfactor, as akinetic off states are prolonged and moresevere in advanced PD. The results reported by Chenand colleagues3 do not support this hypothesis, as theyshowed a longitudinally increased energy intake. Sec-ondly, the observed time course of weight loss in thestudy by Chen and colleagues3 conflicts with the con-cept of enduring akinetic states as a significant causeof weight loss, because progression of PD is longitu-dinally associated with increasing duration of akineticoff states. Before the first occurrence of PD symptoms,observations of weight loss are vague, as the data areretrospective.

NEUROENDOCRINOLOGY OF APPETITEREGULATION

The finding of increased resting energy expenditure,even in those PD patients with minimal rigidity or opti-mally treated patients,15 and the failure to show a con-sistent correlation between parkinsonian motor symp-toms and energy metabolism suggest that an underlyingneuroendocrinological dysregulation in PD patients maybe one factor contributing to weight loss. A variety offactors influence eating behavior. The paraventricularnucleus (PVN) and arcuate nucleus in the ventromedialhypothalamus are elements of a system coordinatingbody composition with energy expenditure and energyingestion.28 Several afferent neural (vagal and cat-echolaminergic) and hormonal impulses (e.g., insulin,leptin) associated with metabolic condition reach thehypothalamus, where they mediate the secretion of pep-tides that influence eating behavior. Corticotropin-releas-ing hormone (CRH), for example, is involved in theregulation of eating behavior and exerts an anorexigeniceffect via the bed nucleus of the stria terminalis(BNST).29 Emotional stress and restraint stress in rats,experimentally induced with an immobilization cage,inhibit their food intake through CRH.30 Moreover, ani-mal studies demonstrate that selective CRH 2 receptoractivation represses food intake, and central applicationof a selective CRH 1 receptor agonist evokes short-onsetanorexia.31 These findings suggest that conditions thatare associated with increased central CRH concentra-tions could be accompanied by decreased food intake.

OREXINS AND REGULATION OF FEEDING

Signaling pathways from the lateral hypothalamus tothe ventral tregmental area (VTA) involve afferent neu-rons containing the neuropeptides orexin-A and -B.32

Besides stimulating feeding, orexins augment energy ex-penditure due to an increase in locomotor activity.33

Central administration of orexin-A results in a rise inlocomotor activity and arousal and a short-termed in-crease in food intake.34 It is tempting to hypothesize thata defect in orexin-A transmission may be associated withPD. Drouot and colleagues35 detected lower orexin-Aventricular CSF concentrations in PD patients comparedto controls and showed that CSF orexin-A concentrationseven decline in the course of the disease. These resultsindicate a complex central signaling system to controlfeeding behavior.

Leptin, a peptide hormone synthesized by adiposetissue, is an important controller of energy homeostasisand may affect the central regulation of feeding. Inparkinsonian patients with unintended weight loss, how-ever, serum leptin concentrations were not significantly

BODY WEIGHT 1827


different from PD patients with stable body weight.36

This finding contrasts with the higher CSF plasma leptinratios in anorexia nervosa patients.37

Injection of neuropeptide Y (NPY), a protein involvedin the regulation of neuroendocrine axes and circadianrhythms, into different hypothalamic and extrahypotha-lamic loci results in increased food intake,38 clearly sug-gesting that NPY is a strong appetite mediator. Canniz-zaro and colleagues39 detected increased NPY mRNAexpression in the nucleus accumbens and caudate nu-cleus in brain slices from PD patients. NPY concentra-tions in the CSF of PD patients have not beendetermined.

GH AND BODY COMPOSITION

Administration of levodopa may stimulate GH secre-tion.40 Thus, in PD patients, dopaminergic medication,e.g., dopamine agonists, may stimulate GH release. Anacute rise can be observed after challenging the systemwith low-dose apomorphine.41 GH in turn may inducelipolysis and ultimately lead to weight loss in parkinso-nian patients.

MESOCORTICOLIMBIC REWARDPROCESSING IN PARKINSON’S DISEASE

Since there is controversy with regard to energy intakevs. expenditure in Parkinson’s disease, it might be pre-mature to rule out the role of decreased reward process-ing. A further hypothesis is that increased weight lossoccurs due to an altered mesocorticolimbic system.Kunig and colleagues14 utilized regional cerebral bloodflow (rCBF) measurements with H2

15O PET and showeda lack of activation of mesocorticolimbic and mesostria-tal pathways after reinforcement and reward in PD pa-tients. Still, the finding of higher energy intake in PDpatients compared to controls contradicts decreased re-ward processing and a consequent decreased food intakeas a major determinant of weight loss in PD.42

NEUROLEPTICS AND BODY WEIGHT GAIN

There is almost no literature on the relationship be-tween neuroleptics and weight in PD patients. Althoughmany studies investigate weight gain induced by neuro-leptic pharmacotherapy in psychotic patients,43 no stud-ies analyzing the effect of neuroleptics in parkinsonianpatients have been performed.

Double-blind multicenter studies suggest that cloza-pine can ameliorate psychosis in PD without worseningmotor symptoms. Clozapine has also been shown toinduce significant weight gain in schizophrenic patientsat doses ranging from 300 to 900 mg.44 When adminis-tered at doses of 221 � 123 and 608 � 187 mg to

schizophrenic patients, no positive correlation betweenbody weight gain and dosage could be observed.45 In PDpatients with psychosis, much lower doses of clozapinewere used (6.25 to 50 mg),44 with an effective mean doseof 28.8 mg/day in the PSYCLOPS trial.46 Unfortunately,body weight changes were not reported in PSYCLOPS,46

and no longitudinal studies on body weight changes inPD patients with dopamine-induced psychosis receivingclozapine treatment have been performed.

Parkinsonian patients have an increased risk of fall-ing.47,48 They are at high risk for bone fractures6,49 andassociated serious life-threatening complications, e.g.,pneumonia. The severity of bone fractures resulting froma fall is increased in patients with osteoporosis,50 and lowbone mineral density is correlated with low BMI inparkinsonian patients.6 Both osteoporosis and low bodymass index are risk factors for hip fractures.51 Patientswith PD, especially females with low BMI, are probablyat high risk for bone fractures.6 As the population ofWestern countries ages, the number of patients with PDwill increase. It is urgent that the major factors in thepathophysiology of weight loss in PD patients be clari-fied. Several studies point to an important role of motorsymptoms associated with increased energy expenditure,whereas other studies could not detect any relation be-tween these parameters.

The failure to demonstrate consistently a correlationbetween energy homeostasis and clinical parameters sug-gests a neuroendocrinological dysregulation of energyhomeostasis in PD patients as one important determinantin the reported weight loss. Signaling pathways andmolecules known to be involved in the regulation ofenergy intake, e.g., hypothalamia pituitary adrenocortical(HPA) axis activity, NPY, GH, leptin, orexin-A and -B,need to be investigated.

PRACTICAL RECOMMENDATIONS FORTREATMENT REGIMENS IN PD PATIENTS

From the previous studies on body weight and nutri-tion in PD, at least some recommendations can be givento both patients and their doctors. First, there is a need tomonitor closely body weight over time as Parkinson’sdisease progresses3 by measuring the patient’s bodyweight on a monthly basis and keeping weight records,as suggested by previous studies.52 Second, the nutritionof PD patients should include sufficient vitamin D sup-plementation between 700 and 800 IU/day and calciumat 1,200 mg/day to reduce the risk of hip fractures andseverely disabling scoliosis due to osteoporosis and axialdeformation.6,53,54 We are not able to provide recommen-dations regarding physical therapy and exercise. Physicaltherapy and exercise are topics that exceed the parame-



ters of this review, though we acknowledge that both arevery important subjects that need to be addressed. Dietsupplementation with vitamin C and vitamin E does notreduce disease progression, nor does it improve the clin-ical symptomatology of Parkinson’s disease.55 The sameis true for vitamin B6, B12, and folic acid, as studies onthe effects of these vitamins56 and folic acid56,57 haveproven. It should also be noted that fluid intake should besupervised, and we recommend at least 1.6 l water/day58

because water intake in PD patients is significantly de-creased and is associated with constipation, which maylead to severe complications.59 As has been demon-strated, levodopa competes with amino acids for trans-port across the blood–brain barrier,60 and PD patientsmay notice that meals with a high protein content affectthe efficacy of their levodopa medication. Under suchcircumstances, PD patients may benefit from a proteinredistribution diet.61 Practically speaking, PD patientsmay benefit most by taking their levodopa-containingmedication 1 hour before meals, because long-term re-strictive diets increase the likelihood of other nutrition-related conditions, e.g., osteoporosis, especially for PDpatients who are already at risk from this condition.62,63

Most important, fluctuating PD patients need a flexiblefood schedule, because mealtimes may interfere with offperiods associated with akinesia and impaired hand–mouth coordination. Since fluctuations may occur unpre-dictably, institutional food schedules should be avoidedand meal assistant strategies should be provided to insti-tutionalized seniors with Parkinson’s disease. Future rec-ommendations based on clinical studies of weight regu-lation and nutrition in PD patients are warranted.

Acknowledgments: We thank Ms. Christine Crozier andMr. Alan Oberlin for language editing.

REFERENCES

1. Abbott RA, Cox M, Markus H, Tomkins A. Diet, body size andmicronutrient status in Parkinson’s disease. Eur J Clin Nutr 1992;46:879–884.

2. Beyer PL, Palarino MY, Michalek D, Busenbark K, Koller WC.Weight change and body composition in patients with Parkinson’sdisease. J Am Diet Assoc 1995;95:979–983.

3. Chen H, Zhang SM, Hernan MA, Willett WC, Ascherio A. Weightloss in Parkinson’s disease. Ann Neurol 2003;53:676–679.

4. Horber FF, Gruber B, Thomi F, Jensen EX, Jaeger P. Effect of sexand age on bone mass, body composition and fuel metabolism inhumans. Nutrition 1997;13:524–534.

5. Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin Ddeficiency and reduced bone mass in Parkinson’s disease. Neurol-ogy 1997;49:1273–1278.

6. Sato Y, Kaji M, Tsuru T, Oizumi K. Risk factors for hip fracturesamong elderly patients with Parkinson’s disease. J Neurol Sci2001;182:89–93.

7. Margolis DJ, Knauss J, Bilker W, Baumgarten M. Medical condi-tions as risk factors for pressure ulcers in an outpatient setting. AgeAgeing 2003;32:259–264.

8. Wehren LE, Hawkes WG, Orwig DL, Hebel JR, Zimmerman SI,Magaziner J. Gender differences in mortality after hip fracture: therole of infection. J Bone Miner Res 2003;18:2231–2237.

9. Guttman M, Slaughter PM, Theriault ME, DeBoer DP, Naylor CD.Parkinsonism in Ontario: comorbidity associated with hospitaliza-tion in a large cohort. Mov Disord 2004;19:49–53.

10. Muller A, Mungersdorf M, Reichmann H, Strehle G, Hummel T.Olfactory function in Parkinsonian syndromes. J Clin Neurosci2002;9:521–524.

11. Muller J, Wenning GK, Verny M, et al. Progression of dysarthriaand dysphagia in postmortem-confirmed Parkinsonian disorders.Arch Neurol 2001;58:259–264.

12. Tanner CM, Goetz CG, Klawans HL. Autonomic nervous systemdisorders in Parkinson’s disease. In: Koller W, editor. Handbook ofParkinson’s Disease. New York: Marcel Dekker; 1987. p 152–169.

13. McDonald WM, Richard IH, DeLong MR. Prevalence, etiology,and treatment of depression in Parkinson’s disease. Biol Psychiatry2003;54:363–375.

14. Kunig G, Leenders KL, Martin-Solch C, Missimer J, Magyar S,Schultz W. Reduced reward processing in the brains of parkinso-nian patients. Neuroreport 2000;11:3681–3687.

15. Markus HS, Cox M, Tomkins AM. Raised resting energy expen-diture in Parkinson’s disease and its relationship to muscle rigidity.Clin Sci 1992;83:199–204.

16. Markus HS, Tomkins AM, Stern GM. Increased prevalence ofundernutrition in Parkinson’s disease and its relationship to clinicaldisease parameters. J Neural Transm Park Dis Dement Sect 1993;5:117–125.

17. Ondo WG, Ben-Aire L, Jankovic J, Lai E, Contant C, Grossman R.Weight gain following unilateral pallidotomy in Parkinson’s dis-ease. Acta Neurol Scand 2000;101:79–84.

18. Gironell A, Pascual-Sedano B, Otermin P, Kulisevsky J. Weightgain after functional surgery for Parkinson’s disease. Neurologia2000;17:310–316.

19. Vitek JL, Bakay RA, Freeman A, et al. Randomized trial ofpallidotomy versus medical therapy for Parkinson’s disease. AnnNeurol 2003;53:558–569.

20. Barichella M, Marczeska AM, Mariani C, Landi A, Vario A,Pezzoli G. Body weight gain rate in patients with Parkinson’sdisease and deep brain stimulation. Mov Disord 2003;18:1337–1340.

21. Macia F, Perlemoine C, Coman I, et al. Parkinson’s disease pa-tients with bilateral subthalamic deep brain stimulation gainweight. Mov Disord 2004;19:206–212.

22. Levi S, Cox M, Lugon M, Hodkinson M, Tomkins A. Increasedenergy expenditure in Parkinson’s disease. Br Med J 1990;301:1256–1257.

23. Toth MJ, Fishman PS, Poehlman ET. Free-living daily energyexpenditure in patients with Parkinson’s disease. Neurology 1997;48:88–91.

24. Arabia G, Zappia M, Bosco D, et al. Body weight, levodopapharmacokinetics and dyskinesia in Parkinson’s disease. NeurolSci 2002;23:S53–S54.

25. Lang AE, Lozano A, Tasker R, Duff J, Saint-Cyr J, Trepanier L.Neuropsychological and behavioral changes and weight gain aftermedial pallidotomy. Ann Neurol 1997;41:834–836.

26. Moro E, Scerrati M, Romito LM, Roselli R, Tonali P, Albanese A.Chronic subthalamic nucleus stimulation reduces medication re-quirements in Parkinson’s disease. Neurology 1999;53:85.

27. Vardi J, Oberman Z, Rabey I, Streifler M, Ayalon D, Herzberg M.Weight loss in patients treated long-term with levodopa. J NeurolSci 1976;30:33–40.

28. Kalra SP, Dube MG, Shuye P, Xu T, Horvath TL, Kalra PS.Interacting appetite-regulating pathways in the hypothalamic reg-ulation of body weight. Endocr Rev 1999;20:68–100.

29. Ciccocioppo R, Fedeli A, Economidou D, Polcani F, Weiss F,Massi M. The bed nucleus is a neuroanatomical substrate for theanorectic effect of corticotropin-releasing factor and for its reversalby nociceptin/orphanin FQ. J Neurosci 2003;23:9445–9451.

BODY WEIGHT 1829


30. Shibasaki T, Yamauchi N, Kato Y, et al. Involvement of cortico-tropin-releasing factor in restraint stress-induced anorexia and re-version of the anorexia by somatostatin in the rat. Life Sci 1988;43:1103–1110.

31. Zorilla EP, Tache Y, Koop G. Nibbling at CRF receptor control offeeding and gastroclonic motility. Trends Pharmacol Sci 2003;24:421–427.

32. Fadel J, Deutch AY. Anatomical substrates of orexin-dopaineinteractions: lateral hypothalamic projections to the ventral teg-mental area. Neuroscience 2002;111:379–387.

33. Willie JT, Chemelli Rm, Sinton CM, Yanagisawa M. To eat or tosleep? orexin in the regulation of feeding and wakefulness. AnnuRev Neurosci 2001;24:429–458.

34. Yamanaka A, Sakurai T, Katsumoto T, Yanagisawa M, Goto K.Chronic intracerebroventricular administration of orexin-A to ratsincreases food intake in daytime, but has no effect on body weight.Brain Res 1999;849:248–252.

35. Drouot X, Moutereau S, Nguyen JP, et al. Low levels of ventricularCSF orexin/hypocretin in advanced PD. Neurology 2003;61:540–543.

36. Evidente VG, Caviness JN, Adler CH, Gwinn-Hardy KA, PratleyRE. Serum leptin concentrations and satiety in Parkinson’s diseasewith and without weight loss. Mov Disord 2001;16:924–927.

37. Mantzoros CS, Flier JS, Lesem MD, Brewerton TD, Jimerson DC.Cerebrospinal fluid leptin in anorexia nervosa: correlation withnutritional status and potential role in resistance to weight gain.J Clin Endocrinol Metab 1997;82:1845–1851.

38. Stanley BG, Chin AS, Leibowitz SF. Feeding and drinking elicitedby central injection of neuropeptide Y: evidence for a hypotha-lamic site(s) of action. Brain Res Bull 1985;14:521–524.

39. Cannizzaro C, Tel BC, Rose S, Zeng BY, Jenner P. Increasedneuropeptide Y mRNA expression in striatum in Parkinson’s dis-ease. Brain Res Mol Brain Res 2003;110:169–176.

40. Hanew K, Utsumi A. The role of endogenous GHRH in arginine-,insulin-, clonidine- and L-dopa-induced GH release in normalsubjects. Eur J Endocrinol 2002;146:197–202.

41. Friess E, Kumpfel T, Winkelmann J, et al. Growth-hormone re-sponse to apomorphine is increased in Parkinson’s disease com-pared with multiple system atrophy. Arch Neurol 2001;58:241–246.

42. Lorefalt B, Ganowiak W, Palhagen S, Toss G, Unosson M, Gran-erus AK. Factors of importance for weight loss in elderly patientswith Parkinson’s disease. Acta Neurol Scand 2004;110:180–187.

43. Allison DB, Casey DE. Antipsychotic-induced weight gain: areview of the literature. J Clin Psychiatry 2001;62:22–31.

44. Friedman JH, Factor SA. Atypical antipsychotics in the treatmentof drug induced psychosis in Parkinson’s Disease. Mov Disord2000;15:201–211.

45. Jalenques I, Tauveron I, Albuisson E, Audy V, Fleury-Duhamel N,Coudert AJ. Weight gain as a predictor of long-term clozapineefficacy. Clin Drug Invest 1996;12:16–25.

46. Factor SA, Friedman JH, Lannon MC, Oakes D, Bourgeois K,Parkinson Study Group. Clozapine for the treatment of drug-induced psychosis in Parkinson’s disease: results of the 12 weekopen label extension in the PSYCLOPS trial. Mov Disord 2001;16:135–139.

47. Cano-de la Cuerda R, Macias-Jimenez AI, Cuadrado-Perez ML,Miangolarra-Page JC, Morales-Cabezas M. Posture and gait dis-orders and the incidence of falling in patients with Parkinson. RevNeurol 2004;38:1128–1132.

48. Stolze H, Klebe S, Zechlin C, Baecker C, Friege L, Deuschl G.Falls in frequent neurological diseases: prevalence, risk factors andaetiology. J Neurol 2004;251:79–84.

49. Johnell O, Melton LJ III, Atkinson EJ, O’Fallon WM, Kurland LT.Fracture risk in patients with parkinsonism: a population-basedstudy in Olmsted County, Minnesota. Age Ageing 1992;21:32–38.

50. Toretta P III, Hirsch EF, Howard R, McConnell T, Ross E. Skel-ettal injury patterns in older females. Clin Orthop Relat Res 2004;422:55–56.

51. Taylor BE, Schreiner PJ, Stone KL, et al. Long-term prediction ofincident hip fracture risk in elderly white women: study of osteo-porotic fractures. J Am Geriatr Soc 2004;52:1479–1486.

52. Keller HH, Gibbs AJ, Boudreau LD, Goy RE, Pattillo MS, BrownHM. Prevention of weight loss in dementia with comprehensivenutritional treatment. J Am Geriatr Soc 2003;51:945–952.

53. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calciumto prevent hip fractures in elderly women. N Engl J Med 1992;372:1637–1642.

54. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Di-etrich T, Dawson-Hughes B. Fracture prevention with vitamin Dsupplementation: a meta-analysis of randomized controlled trials.JAMA 2005;293:2257–2264.

55. Vilming ST. Diet therapy in Parkinson disease. Tidsskr Nor Lae-geforen 1995;115:1244–1247.

56. Ahlskog JE. Parkinson’s disease: new treatment strategies. CompTher 1990;16:41–46.

57. Chen H, Zhang SM, Schwarzschild MA, Hernan MA, LogroscinoG, Willett WC, Ascherio A. Folate intake and risk of Parkinson’sdisease. Am J Epidemiol 2004;160:368–375.

58. Hodgkinson B, Evans D, Wood J. Maintaining oral hydration inolder adults: a systematic review. Int J Nurs Pract 2003;9:19–28.

59. Ueki A, Otsuka M. Life style risks of Parkinson’s disease: asso-ciation between decreased water intake and constipation. J Neurol2004;251(Suppl. 7):18–23.

60. Carter J, Nutt J. Dietary issues in Parkinson’s disease. In: KollerW, Paulson G, editors. Therapy of Parkinson’s Disease. New York:Marcel Dekker; 1995. p 443–461.

61. Pare S, Barr SI, Ross SE. Effect of daytime protein restriction onnutrient intakes of free-living Parkinson’s Disease patients. Am JClin Nutr 1992;55:701–707.

62. Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, SatohK. Amelioration of osteoporosis by menatetrenone in elderly fe-male Parkinson’s disease patients with vitamin D deficiency. Bone2002;31:114–118.

63. Woo J. Relationships among diet, physical activity and otherlifestyle factors and debilitating diseases in the elderly. Eur J ClinNutr 2000;54(Suppl. 3):S143–S147.

64. Wenning GK, Shepard B, Hawkes C, Petruckevitch A, Lees A,Quinn N. Olfactory function in atypical parkinsonian syndromes.Acta Neurol Scand 1995;91:247–250.



Documents

Body weight in patients with Parkinson's disease