Received: 28 May 2016

| Revised: 31 October 2016 | Accepted: 2 November 2016

DOI: 10.1002/brb3.616

ORIGINAL RESEARCH

Weight loss in the early stage of progressive supranuclear palsy
Ayako Tsuge1 | Satoshi Kaneko1 | Reika Wate1 | Mitsuaki Oki1 |Masato Nagashima1 | Shinya Asayama1 | Masataka Nakamura1 | Kengo Fujita1 |Akemi Saito1 | Norihiro Takenouchi2 | Hirofumi Kusaka1
1
Department of Neurology, Kansai Medical
University, Hirakata, Osaka, Japan2
Department of Microbiology, Kansai Medical
University, Hirakata, Osaka, Japan

Correspondence
Satoshi Kaneko, Department of Neurology,
Kansai Medical University, Hirakata, Osaka,
Japan.
Email: kanekosa@takii.kmu.ac.jp

Abstract
Objectives: To clarify whether weight change in patients with Parkinson’s disease (PD)or progressive supranuclear palsy (PSP) is caused by the disease itself or secondarily
by other factors.
Materials and Methods: We conducted a retrospective analysis of 51 patients with
PD and 14 patients with PSP, especially during the early stage of their diseases. All
patients were independent in terms of their activities of daily living and did not haveany feeding difficulty.
Results: The body mass index measured within 3 years after the disease onset did notshow a significant difference between the two diseases. However, the subsequent
weight was stable in patients with PD and significantly decreased in patients with PSP.
Conclusions: Weight loss begins in the early stage of PSP, whereas dopaminergic
treatment may contribute to keep weight in the early stage of PD through reductionof energy expenditure and/or improvement in appetite.
KEYWORDS

movement disorders, neurodegenerative disorders, Parkinson’s disease, progressive
supranuclear palsy

1 | INTRODUCTION

complex. Moreover, the time course of weight changes or comparisonof such change among other neurodegenerative diseases presenting

Weight loss in patients with neurodegenerative diseases is frequently
observed and affects the patients’ prognosis. A cause-­related andas parkinsonism has never been reported.
Here, we report a comparative study on weight change in patientspatient-­tailored treatment can improve the quality of life (Aziz et al.,with PD or PSP, and discuss the pathophysiology of the weight change2008), but the underlying pathomechanism of weight loss is multifac-

in these neurodegenerative diseases. To exclude the complex path-torial. Whether this weight loss is primarily due to the disease itself

omechanism at work in advanced stages, we focused on the earlyor is secondarily caused by decreased food intake, depression, dys-

stages of these diseases.

phagia, dysfunctions in the gastrointestinal system, or side effects ofmedication has not been well investigated. Changes in the body massindex (BMI) of patients with dysphagia due to Parkinson’s disease (PD)2 | PATIENTS AND METHODS

or progressive supranuclear palsy (PSP) have been reported (Jankovic,
Wooten, Van der Linden, & Jansson, 1992), but these patients werePatients with PD or PSP in our outpatient departments were enrolled

in an advanced stage of their disease, and their pathophysiology wasin this study. All subjects gave their written informed consent to thisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,provided the original work is properly cited.
© 2016 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
Brain and Behavior 2016; e00616

wileyonlinelibrary.com/journal/brb3|

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TSUGE et al.

study, which was approved by the local ethics committee. Clinical di-

1. BMI1 values were compared between PD and PSP patients.

agnoses were made according to the established diagnostic criteria

2. ∆BW was evaluated for each disease.

for PD (Hughes, Daniel, Kilford, & Lees, 1992) and PSP (Litvan et al.,1996).

Statistical analysis of BMI1 was done by performing the Mann–

Weight can be influenced by many factors, and therefore we focused on the early stages of these diseases and set up criteria for dis-

Whitney test and that of ∆BW, by use of the paired-­t test and Wilcoxon
test. Statistical significance was set at p < .05.

ease duration: (1) the first measurement of weight was made within
3 years from the onset of extrapyramidal symptoms and (2) the interval
between the first and the second measurements of weight was within

3 | RESULTS

3 years. According to these criteria, we conducted a retrospective study.
All patients were independent in terms of activities of daily living up

Profiles of the patients are summarized in Table 1. All patients withto the second measurement of weight. To exclude the possibilities of

PSP were diagnosed as Richardson type based on the criteria. Meanother factors affecting the body weight, patients with dysphagia treatedages at the onset of disease were 67.1 ± 7.4 (mean ± SD) years forby percutaneous endoscopic gastrostomy and those who had a past

PD and 69.4 ± 6.3 for PSP. Disease duration at the first measure-

medical history of endocrine-­metabolic disease, malignancy, depression,

ment of weight was 1.4 ± 0.8 years for PD and 1.7 ± 1.0 for PSP, andbone fracture, or orthopedic surgery were excluded. As serotonin canthere was no statistically significant variation between them (Mann–affect the appetite and body weight, patients treated with antidepres-Whitney test).

sants such as selective serotonin reuptake inhibitors (SSRI) and/or serotonin norepinephrine reuptake inhibitors (SNRI) were also excluded.

Some patients were already being medicated for parkinsonism at the time of the first measurement: two male patients (LED,Clinical diagnosis, gender, age of disease onset, date of first visit,

370.8 ± 5.9 mg) and two female patients (LED, 75.0 ± 35.4 mg)

and medication were recorded on the entry sheets. All patients with

with PD, one male patient (LED, 200 mg) with PSP. At the time

PD were evaluated with the Unified Parkinson’s Disease Rating Scaleof the second measurement, medication was being given to 18(UPDRS). All patients with PSP were evaluated with PSP rating scale

male patients (LED, 289.6 ± 121.5 mg) and 29 female patients(PSPRS; Golbe & Ohman-­Strickland, 2007). Doses of anti-­parkinsonian(LED, 217.9 ± 153.3 mg) with PD and to 2 male patients (LED,drugs were converted to their levodopa equivalent dose (LED) ac-

250 ± 71 mg) with PSP. At the time of the second measurement, 30

cording to a previously reported conversion formula (Tomlinson et al.,patients with PD were treated with dopamine agonists (19 patients

2010).

treated with pramipexole and 11 patients treated with ropinirole).

The first weight, BMI and the second weight were abbreviated asNone of patients with PSP was treated with dopamine agonists.

BW1 (kg), BMI1 (kg/m2) and BW2 (kg), respectively. As the BMI can be

According to the medical records and patients interview, all pa-

influenced by a forward bend posture or by osteoporosis, the change

tients did not have any symptoms of depression, apathy, anorexia,

in weight was evaluated as that in the weight itself, which was calcu-

or hyperphagia.

lated as ∆BW (=BW2 − BW1).

The mean UPDRS Part III scores of the patients with PD at theData were analyzed as follows:

TABLE 1time of BW 1 and BW2 were 23.2 ± 9.5 and 17.7 ± 7.8, respectively.

Profiles of patients with Parkinson’s disease (PD) and progressive supranuclear palsy (PSP)PD

PSP

p Value

Total

Male

Female

Total

Male

Female

Total

Male

FemaleNumber ofpatients

51

19

32

14

8

6

Age at onset(years)67.1 ± 7.4

67.3 ± 6.4

67.0 ± 8.0

69.4 ± 6.3

72.3 ± 5.6

65.4 ± 5.0

.243

.055

.645

Age at BW1(years)68.5 ± 7.3

68.9 ± 6.6

68.3 ± 7.8

71.0 ± 6.4

74.0 ± 6.0

67.1 ± 4.9

.240

.056

.733

Age at BW2(years)70.3 ± 7.5

70.8 ± 6.7

70.0 ± 7.9

72.8 ± 6.4

75.6 ± 6.2

69.1 ± 4.9

.210

.104

.968

Disease duration
at BW1 (years)

1.4 ± 0.8

1.6 ± 0.7

1.2 ± 0.8

1.7 ± 1.0

1.6 ± 1.0

1.7 ± 1.1

.281

.915

.279

Disease duration
at BW2 (years)

3.2 ± 1.1

3.5 ± 1.0

3.0 ± 1.0

3.4 ± 1.9

3.3 ± 1.9

3.5 ± 2.0

.719

.631

.470

LED at BW2 (mg)243.7 ± 145.6

289.6 ± 121.5

217.9 ± 153.3

Values are mean ± standard deviation. LED, levodopa equivalent dose. BW1, BW2, body weight at the first and the second measurement.
p Value of variables comparing PD and PSP.

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TSUGE et al.

The mean PSPRS scores for bulbar symptoms at the time of BW1
and BW2 were 0.8 ± 0.4 and 1.5 ± 0.5, respectively. All patients
did not have difficulty in dietary intake at the time of BW1 andBW2.
BW1, BW2, BMI1, ∆BW, and intervals between the first and thesecond measurements are indicated in Table 2. BMI1 values, which

4 | DISCUSSION
We investigated the change in weight of patients with PD and PSP in
the early stage of their diseases. Comparison of the BMI1 measured
within 3 years after disease onset did not show any significant differ-

were measured in the very early stage and thus under little effect ofence between PD and PSP. However, the temporal change in weight

medication, were 22.3 ± 3.4 kg/m2 for PD and 23.2 ± 3.2 kg/m2 for

was obviously different between these patients; that is, there was asignificant decrease in the weight of PSP patients, whereas the weightPSP.
Body mass index in the range from 18.5 to 25 is classified as “nor-of the PD patients remained stable, showing no significant change.

mal weight” according to WHO criteria. Therefore, 65% of PD and

Loss of weight as a nonmotor symptom of PD has been previously

64% of PSP patients were categorized as having a “normal weight” inmentioned in several reports. Patients with a longer medical history ofthis study (Figure 1). No statistical differences among BMI1 of PD andthe disease show a greater decrease in the mass of body fat (Sakajiri

PSP were observed (Mann–Whitney test).
Measurement intervals for ∆BW were 1.8 ± 0.8 years for PD and& Takamori, 1997). Also, triceps skin fold thickness, which indicatesthe calorie reserves stored in the form of fat, was reported to be sig-

1.7 ± 1.0 for PSP, and no statistically significant difference between

nificantly decreased in patients with advanced PD (Beyer, Palarino,

these intervals was observed (Mann–Whitney test). For PD patients,

Michalek, Busenbark, & Koller, 1995). Therefore, weight loss in PD

their ∆BW was −0.5 ± 3.0, indicating no statistically significant differ-patients, especially in advanced stage, may be attributed mainly to theence. However, in the case of PSP patients, ∆BW was −7.3 ± 6.5 kg,

loss of fat, and not to that of muscle. However, loss of muscle vol-which was a statistically significant decrease in weight. The decrease

ume due to sarcopenia and/or frail frequently appears in advanced

in weight was statistically significant for total, male, and female pa-

stage of PD and PSP. It has not yet been settled whether the main

tients with PSP (<.05; Figure 2).

cause of this reduction in fat or muscle is primarily due to the disease

TABLE 2

Results of patients with Parkinson’s disease (PD) and progressive supranuclear palsy (PSP)PD

PSP

p Value

Total

Male

Female

Total

Male

Female54.3 ± 8.5

58.9 ± 5.7

51.7 ± 8.8

58.6 ± 8.0

60.2 ± 9.1

56.5 ± 6.3

BMI1 (kg/m )22.3 ± 3.4

22.2 ± 2.6

22.4 ± 3.8

23.2 ± 3.2

22.5 ± 3.9

24.2 ± 2.0

BW2 (kg)

53.8 ± 8.6

58.2 ± 6.9

51.3 ± 8.6

51.3 ± 9.2

54.5 ± 9.8

47.1 ± 6.8

BW1 (kg)
2

2

Total

Male

FemaleBMI2 (kg/m )22.4 ± 3.5.7

22.3 ± 3.1

22.4 ± 3

20.7 ± 3.3

20.9 ± 3.9

20.6 ± 2.8

ΔBW (kg)−0.5 ± 3.0−0.7 ± 3.4−0.4 ± 2.9−7.3 ± 6.5−5.6 ± 5.7−9.4 ± 7.3

<.001

.007

.003

Interval between BW1
and BW2 (years)

1.8 ± 0.8

1.9 ± 0.7

1.7 ± 0.8

1.7 ± 1.0

1.7 ± 1.0

1.8 ± 1.0

.695

.471

.904

Values are mean ± standard deviation. BW1, BW2, body weight at the first and the second measurement. BMI1, BMI at the first measurement. ΔBW,
BW2 − BW1.
p Value of variables comparing PD and PSP.

F I G U R E 1 Comparison of BMI1 between Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). Dotted lines indicate the normal
range of BMI according to WHO criteria. Each box plot shows the median, 25th and 75th percentiles. Whiskers indicate the 5th and 95th
percentiles

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TSUGE et al.

PDBW(kg) 80

P=0.473

total

90

male

80

P=0.812

90

70

70

70

60

60

60

50

50

50

40

40

40

30

90

BW
(kg) 80

BW1

30

BW2

PSP

BW1

90

total

P=0.00130

BW2

P=0.012

70

70

60

60

60

50

50

50

40

40

40

BW1

BW2

30

P=0.451

BW2

P=0.027

female

80

70

30

BW1

90

male

80

female

80

30

BW1

BW2

BW1

BW2

F I G U R E 2 Weight change in Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). Lines indicate the weight change between
BW1 and BW2 of individual patients
itself or is secondarily caused by reduced food intake or side effects

Appetite of patients with PD might have been improved by dopami-of medication.

nergic treatment (Aiello, Eleopra, & Rumiati, 2015). On the other hand,

A change in weight is thought to result from a disturbed balance
between energy intake and energy expenditure (Aziz et al., 2008).

since most of PSP patients have not received dopamine treatment, it is
not likely that medication has affected their change in weight.

Decreased energy intake can be caused by disturbed olfaction or

In the early stages of PD and PSP, the energy expenditure, may betaste, depression, dysphagia, eating difficulty due to parkinsonism,

different and mainly affect the change in weight. Energy expenditureslowing of gastric emptying time, decreased motility of the gastro-is supposedly promoted in PSP. Reduction of energy expenditure and/intestinal tract, or impaired absorption (Pfeiffer, 2003). Especially,or improvement in appetite by dopaminergic treatment may contrib-

dysphagia severely affects the amount of food intake. The BMI of PD

ute to keep weight in the early stages of PD. Hypothalamic neuro-

patients with dysphagia was earlier reported to show a significantly

peptides, which control the general metabolism; leptin, an adipose

greater decrease than that of PD patients without dysphagia (Nozaki,

tissue-­derived hormone that regulates body-­fat mass; and disease-­

Saito, Matsumura, & Miyai, 1999). In this study, it is noteworthy thatspecific neuropathological changes in the hypothalamus, should be

the weight of patients with PSP in its early stage decreased, in spite ofinvestigated in a future study.

exclusion of patients suffering feeding difficulty. An increase in energy
expenditure can be caused by resting tremor or muscle rigidity. PD andPSP patients have, more or less, increased energy expenditure due totremor and/or rigidity (Levi, Cox, Lugon, Hodkinson, & Tomkins, 1990).

AC KNOW L ED G M ENTS
This work was supported by internal funds only.

However, we could not analyze the source of the disturbance in energy balance in relation to weight change in this study.
Dopaminergic treatment is reported to be associated with decreased weight in patients with advanced PD (Bachmann, Zapf, Brunner,

CO NFL I C T O F I NT ER ES T
The authors have no conflict of interest to report.

& Trenkwalder, 2009). In this study, we focused on the early stages of
PD and PSP, and medication had not been started at the time BW1
was measured in almost all of the patients. However, almost all of the
PD patients were treated with anti-­parkinsonian drugs by the time thatBW2 was determined. Therefore, there is a possibility of the protective effect of medication on the weight of the PD patients, who maintained a stable weight. Appropriate treatment of tremor and rigidity inthe early stages of PD might have reduced the energy consumption.

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How to cite this article: Tsuge, A., Kaneko, S., Wate, R., Oki, M.,
Nagashima, M., Asayama, S., Nakamura, M., Fujita, K., Saito, A.,
Takenouchi, N. and Kusaka, H. (2016), Weight loss in the early stageof progressive supranuclear palsy. Brain and Behavior, 00: 1–5.
e00616, doi: 10.1002/brb3.616