Clinical Nutrition xxx (2014) 1e8

Contents lists available at ScienceDirect

Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Weight gain and increased central obesity in the early phase of

Parkinson’s disease
Magdalena Vikdahl a, *, Maine Carlsson b, Jan Linder c, Lars Forsgren c, Lena Håglin a
a
Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, SE-901 87 Umeå, Sweden
b
Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, SE-901 87 Umeå, Sweden
c
Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Weight loss is strongly associated with Parkinson’s disease (PD) and impacts
Received 11 July 2013 symptoms and disease progression. The aim of this study was to describe changes in body composition
Accepted 28 December 2013 and to explore how body weight (BW), relates to disease progression and medication in the early phase
of PD.
Keywords: Methods: Participants in a prospective community-based caseecontrol study of PD were followed-up
Anthropometry
three years after initial diagnosis. Anthropometric and bioelectrical impedance spectroscopy (BIS)
Body composition
measurements were used together with Mini Nutritional Assessment (MNA), a 24-h recall (24-HR) and a
Body weight
Nutrition
3-day food registration (3-DFR) to complete the evaluation of nutritional status. Disease severity was
Parkinson’s disease assessed using the Mini Mental State Examination (MMSE), the Unified Parkinson’s Disease Rating Scale
motor score (UPDRS III), and the Hoehn and Yahr rating.
Results: The PD patients’ BW gained 1.62 kg (
4.60, P ¼ 0.009), an increase that significantly correlated
with fat mass (FM) (r ¼ 0.74), waist size (r ¼ 0.65), waist/height ratio (r ¼ 0.64), and total skin fold
(r ¼ 0.77). Linear regression showed an association between change in BW and physical activity level
(PAL) (B ¼ 8.554; P ¼ 0.025) confirmed by the multiple linear regression. Linear regression also
revealed an association between change in FM and MMSE (B ¼ 0.654; P ¼ 0.027).
Conclusion: In early PD, weight gain was revealed over three years accompanied by an increase in FM and
waist circumference. An inverse relation was revealed between change in BW and PAL. The MMSE,
UPDRS III, and Hoehn and Yahr rating were unchanged. Medication and swallowing difficulties were not
associated with change in BW.
Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Introduction symptoms to dopaminergic medication may contribute to loss

Body weight (BW) and body mass index (BMI) are often lower
in patients with Parkinson’s disease (PD) compared to healthy
controls, particularly in PD patients with more advanced dis-
ease.1 Numerous factors related both to motor and non-motor
Abbreviations: PD, Parkinson’s disease; BW, body weight; BMI, body mass index;
24-HR, 24-h recall; 3-DFR, three-day food registration; MNA, mini nutritional
assessment; MMSE, mini mental state evaluation; UPDRS III, Unified Parkinson’s
Disease Rating Scale-Motor score; BIS, bioelectrical impedance spectroscopy; FFM,
fat free mass; FFMI, fat free mass index; FM, fat mass; FMI, fat mass index; ECW,
extracellular water; ICW, intracellular water; ICWI, intracellular water index; LED,
levodopa equivalent dose; PAL, physical activity level; MET, metabolic equivalent
task; MAC, mid-upper arm; BSF, biceps skinfold; TSF, triceps skinfold; SSF, sub-
scapular skinfold; SISF, suprailiac skinfold; TD, tremor dominant group; PIGD,
postural instability and gait difficulty; CVD, cardiovascular disease; EI, energy
intake.
* Corresponding author. Tel.: þ46 90 785 23 32; fax: þ46 90 13 79 19.
E-mail address: magdalena.vikdahl@gmail.com (M. Vikdahl).
of BW. A longitudinal study found loss of BW despite increased
energy intake among PD patients, indicating that loss of BW is
caused by increased energy expenditure,2 a result that has been
confirmed,3 but also contradicted.4 The possible natural history
of BW in PD may include both periods with gain of weight and
loss of weight.5 Changes in body composition in connection with
loss of BW reveal predominantly loss of fat mass (FM) in PD
patients, a finding that indicates malnutrition,6,7 but excess
adiposity and reduced lean body mass have also been reported.8
An animal model for studying PD (rats treated with 6-
hydroxydopamine) found that weight loss resulted in loss of
intra-abdominal fat together with low levels of insulin and
higher serum glucose levels.9 In a systematic review, Sheard
et al.noted a great range in the prevalence of malnutrition (0e
24%) and risk of malnutrition (3e60%) in PD patients.10 This
range may partly be due to the methods used to assess nutri-
tional status and reveal an increasing proportion of PD patient

0261-5614/$ e see front matter Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
http://dx.doi.org/10.1016/j.clnu.2013.12.012

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2013.12.012
2 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8

Fig. 1. Flowchart of recruitment of included PD patients and controls.

with a risk of malnutrition during the disease duration. Loss of
smell, appetite, and gastrointestinal disturbances such as con-
stipation or dysphagia are common in PD patients and can cause
low BW and increase the risk of malnutrition.11e13 One study
reported that the number of dysautonomic disturbances, but not
single disturbances (dysphagia, sialorrhea, constipation), was
associated with nutritional deterioration along with the disease
status assessed by Hoehn and Yahr stage and levodopa dose.14
Studies on BW, BMI, and body composition in PD are mainly
cross-sectional and based on selected patients and the results are
inconsistent (i.e., not all studies report a low BMI).1
This longitudinal and community-based study uses traditional
anthropometry and bioelectrical impedance spectroscopy
(BIS) measurements to describe changes in body composition
among PD patients three years after diagnosis. The study also
assesses associations between BW and FM changes, medication
and symptoms related to the disease progress in the early phase
of PD.

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2013.12.012
 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8
2. Materials and methods
2.1. Study population
This community-based prospective study focuses on idio-
pathic forms of parkinsonism in a catchment area (parts of
Västerbotten county in northern Sweden) with 142,000 in-
habitants.15 All suspected cases with idiopathic parkinsonism
were referred to the only neurological department in the area.
The area had no specialists in neurology working in private
practise. From January 2004 through April 2009, 186 cases with
parkinsonism were identified. Patients fulfilling diagnostic
criteria for PD, as described below, were included in the study.
Data were analysed for patients and controls at the time of
baseline assessments and at the 3-year follow-up. To assess
changes in body composition participants who had BW data both
at baseline and at the three-year follow-up were included,
resulting in a group of 58 PD patients and 24 controls. Among
those excluded were six patients with intractable severe tremor
despite optimal dopaminergic treatment, who were treated with
deep brain stimulation (DBS). The DBS treatment was considered
appropriate even early in the disease for these patients given the
limited response of pharmacological treatment on tremor. A
flowchart for participation is presented in Fig. 1.The excluded
population due to missing BW data (n ¼ 87; 30 of these 87
deceased before follow-up) exhibited significant differences in
the Mini-Mental State Examination (MMSE) (1.0, n ¼ 78,
P < 0.001), Mini Nutritional Assessment (MNA) (1.0, n ¼ 44,
P ¼ 0.040), the Unified PD Rating Scale motor score (UPDRS III)
(þ4.6, n ¼ 87, P ¼ 0.014), the Hoehn and Yahr rating (þ0.4, n ¼ 87,
P < 0.001), and age (þ5.3 yrs, n ¼ 87, P ¼ 0.001) compared to the
included PD group (n ¼ 58) at baseline (no significant differences
were found between the groups when the 30 who deceased were
not included in the comparisons). No significant differences
regarding gender, reported energy intake, or BW were discov-
ered. Thirty-one healthy controls were recruited through an
announcement in the local newspaper and were selected ac-
cording to age and sex distribution as in the 50 first PD patients
included.
The study was approved by the Regional Ethical Review Board
for northern Sweden (medical section). Written informed consent
was obtained from all participants.
2.2. Assessments
All participants were extensively examined during repeated
visits the first month following initial contact. Information about
demographics and disease history was obtained. All cases with
suspected idiopathic parkinsonism underwent a standardized
clinical examination by a neurologist specializing in movement
disorders. To confirm the presence of PD, another specialist in
movement disorders (blinded to the assessment of the previous
examiner) evaluated a videotape of the patient undergoing the
UPDRS III examination. Patients were included if both examiners
judged that they had fulfilled the clinical criteria for PD according to
the UK Parkinson’s Disease Society Brain Bank (UK PDSBB)
criteria.16 Motor severity was measured using the UPDRS III17 and
Hoehn and Yahr staging scale18 and swallowing by UPDRS II.17 The
UPDRS scoring was performed with patients in the on phase, when
started on dopaminergic treatment. The MMSE was used as a
screening instrument for global cognition.19
Dopaminergic treatment were recorded and calculated as
levodopa equivalent dose (LED) according to the conversion factors
used by Tomlinson et al.20 At three years there were 24 PD patients
medicated with levodopa, six PD patients had dopamine agonists
Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2013.12.012
3
only and 27 PD patients were treated with both levodopa and ag-
onists. One patient was not treated with any medication at all at
follow-up.
2.3. Traditional anthropometry
Anthropometric data were collected during the initial contact
with the dietician (last author; LH); these data were collected
during the first two months after inclusion in the study and
were also collected after three years. Data were mostly collected
with patients in the “on” phase when patients had minor prob-
lems with tremor. Dyskinetic-type involuntary movements were
rare in this early phase of disease and did not hamper assess-
ments. Anthropometrical assessments; BW (kg), height (cm),
waist and hip circumferences (cm), and skin fold measurement
(mm); were used in addition to BIS to assess body composition.
Body weight was measured to the nearest 0.1 kg using a digital
scale. Height was measured to the nearest 0.5 cm using a stadi-
ometer. BMI was calculated from BW in kg and height in meter
squared (BW, kg/height, m2). Waist/height ratio was calculated in
centimetres.
Circumference measurements in cm were performed with a
flexible measuring tape in the following order: mid-upper arm
(MAC), waist, hip, and calf circumference. Mid-upper arm circum-
ference was measured halfway between the acromion process of
the scapula and the tip of the elbow, using the tape measure to the
nearest 0.5 cm. Calf circumference was measured at the level of the
largest circumference to the nearest 0.5 cm. Waist/hip ratio was
calculated in centimetres. Skinfold thickness (mm) was measured
at four sites on the right side of the body; biceps skinfold (BSF),
triceps skinfold (TSF), subscapular skinfold (SSF), and suprailiac
skinfold (SISF), and total skin fold was calculated. All these mea-
surements were taken using a caliper (Harpenden Skinfold Caliper
HSK-BI, Assist Creative Resources Ltd, Wrexham, UK) as described
by Durnin and Womersley.21
2.4. Mini nutritional assessments
A dietician administered the MNA at baseline and at the three-
year follow-up to screen for malnutrition. This screening tool
contains 18 questions regarding anthropometry, diet and health.
MNA scores between 24 and 30 points indicate optimal nutritional
status, MNA scores between 17 and 23.5 indicate a risk for
malnutrition, and MNA scores <17 indicate malnutrition.
2.5. Bioelectrical impedance spectroscopy
Measurements of fat free mass (FFM, kg) were made using a
multifrequency Bioelectrical Impedance Spectrum (BIS) analyser
and ColeeCole modelling software (Hydra ECF/ICF, Hydra model
4200 Xitron Technologies, San Diego, CA). The BW, height, and sex
were entered in the BIS program according to the operating
manual. Two pairs of electrodes were applied 5 cm apart, one pair
on the right hand/wrist and one pair on the right foot/ankle, after
cleaning the skin with isopropyl alcohol. Cables with clips were
connected to the electrodes. To reduce risk for conductance error,
body composition was measured while the participant was in su-
pine position with arms slightly abducted from the body and legs
separated. Apart from FFM, extracellular water (ECW, l) and intra-
cellular water (ICW, l) measurements were registered. Fat mass was
calculated as the difference between BW and FFM. Indices of FFM
(FFMI; FFM kg/m2) and FM (FMI; FM kg/m2) were normalized by
height. The ratio of ICW/FFM was also calculated to assess the
relative part of muscle mass with ICW as a proxy.
4 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8

2.6. Dietary calculations
The dietician performed the 24-h recall (24 HR) with patients
and controls during their visit to the Department of Neurology at
baseline and at three years. They were asked about their food
consumption the day before the interview. A Food Template
(Matmallen) with photographs and drawings of various foods and
dishes was used to describe portion sizes.22 Standard household
measures or package sizes used for food items were not included.
The participants wrote down food and beverage consumption in a
3-day food registration (3-DFR) at home three days before their
next scheduled visit to the Department of Neurology. To describe
portion sizes, they had access to the same Food Template like the
one they used for the 24 HR. The 3-DFR was performed between
one and five weeks after the visit when anthropometry data and 24
HR were collected. In the study population, seven PD patients
(12.1%) and one control (4.2%) did not perform the 3-DFR at base-
line. Corresponding numbers at the three-year follow-up were ten
PD patients (17.2%) and three controls (12.5%). A 3-DFR/24 HR ratio
within the two groups was calculated separately for amount of
energy (KJ and kcal) and each macronutrient. The ratio was used to
adjust the 24 HR value and replace missing values in the corre-
sponding 3-DFR. Reasons for not completing the 3-DFR were dif-
ficulties in understanding the food registration procedure,
incorrectly filling in the form, or not returning the form. Energy and
macronutrient intakes were calculated with the use of the nutri-
tional software Dietist XP (version 3.2 DkNoSe, Kost- och när-
ingsdata, Bromma, Sweden) based on the National Swedish Food
Composition Table (2011) by the National Food Administration.
patients. The variables included in the model were age, gender, LED,
type of dopaminergic medication (levodopa or dopamine agonist),
BW or FM respectively at baseline and changes in energy intake (EI,
kcal), PAL, MMSE, Hoehn and Yahr and UPDRS III. The program
Predictive Analytics Software (PASW Statistics, version 18.0.3 SPSS
Inc., Chicago IL, USA) was used for the analysis.
3. Results
3.1. Baseline data and non-adjusted changes over three years
Traditional anthropometry and BIS measurements at baseline
did not differ between patients and controls including assessments
of MNA and MMSE (Table 1). Changes over three years revealed that
all anthropometric measurement, except calf significantly
increased in patients. Among controls, waist, total skinfold, and
waist/hip and waist/height ratios increased (Table 2). In patients,
males (n ¼ 26; 72.2%) were more prone to gain weight than females
(n ¼ 8, 36.4%). There were no differences in mean change between
patients and controls in anthropometry, BIS, and assessments
(Table 2). The ratio of ICW/FFM decreased (0.02, P ¼ 0.015) over
three years in PD patients, indicating a loss of skeletal muscle
relative to total FFM.
The PD population were also divided into PD subtypes: a tremor
dominant group (TD) (n ¼ 20) and a group characterized by
Table 1
Baseline characteristics for patients with Parkinson’s disease (PD) and controls
(mean
SD).

Variables PD (n ¼ 58) Controls (n ¼ 24) P

2.7. Physical activity
Age (yrs) 68.4
8.0 68.6
7.0 0.93
Male N (%) 36 (62.1) 13 (54.2)
The participants self-registered their activities when they filled
Female N (%) 22 (37.9) 11 (45.8)
in their 3-DFR and they did this on the same form. For each day, the Anthropometry
participants filled in type of activity in periods of 15 min using a BW (kg) 75.8
11.9 75.0
18.2 0.83
number representing a specific metabolic equivalent task (MET). Height (m) 1.70
0.1 1.72
0.1 0.38
There were 11 intensity levels to choose from, ranging from BMI (kg/m2) 26.3
3.8 25.4
4.9 0.36
Waist (cm)a 91.0
10.8 88.1
15.4 0.35
sleeping to intensive exercise (adapted from Durnin and Pass- Hip (cm)a 100.8
8.3 99.5
7.6 0.54
more).23 The number of minutes multiplied by the corresponding Waist/hip (ratio)a 0.90
0.08 0.88
0.10 0.32
MET value was calculated for the energy expended for each activity. Waist/height (ratio) 0.54
0.1 0.51
0.1 0.10
The sum of MET values divided by 24 h (1440 min) gave a Physical MAC (cm) 31.1
2.5 30.2
3.6 0.18
Calf circumference (cm)b 36.3
2.8 35.1
3.4 0.11
Activity Level (PAL) value and mean PAL for the three days was
Total skinfold (mm) 91.2
27.0 83.8
23.6 0.26
calculated.24 In the PD group, 25 participants did not complete the Bioimpedance
activity registration at baseline or at the three-year follow-up. FFM (kg) 46.6
8.5 44.7
11.5 0.41
FFMI (kg/m2) 16.1
2.5 15.1
2.9 0.09
2.8. Statistics FM (kg) 29.1
9.3 30.3
9.3 0.60
FMI (kg/m2) 10.2
3.5 10.3
3.0 0.85
FM (%) 38.1
9.9 40.3
6.9 0.33
The results are presented as mean with standard deviations ECW (l) 16.6
2.7 16.3
3.8 0.67
(
SD) or median and interquartiles. Independent two-tailed test ICW (l) 19.1
5.3 17.8
5.4 0.34
was used to compare patients and controls and to compare BW and ECW/ICW (ratio) 0.91
0.16 0.94
0.12 0.46
ICWI (l/m2) 6.6
1.9 6.0
1.5 0.16
FM according to medication. Paired samples two-tailed t-test was
Assessments
used to test whether a change in mean (
SD) over three years was MNAc 25.8
2.3 27.0
1.6 0.03
significant within each group. For ordinal data and variables with MMSEd 29.0
1.2 29.0
0.9 0.90
skewed distribution, non-parametric tests were performed: the Hoehn &Yahre 2.0 (2.0; 2.5) e e
ManneWhitney and the Wilcoxon Signed Ranks Test. Bivariate UPDRS III Subtotale 23.5 (18.0; 31.3) e e
UPDRS II Swallowinge 0.0 (0.0; 0.0) e e
correlations were analysed using the Pearson’s correlation coeffi-
cient and Spearman’s coefficient for ordinal data. Partial correla- BW, bodyweight; BMI, Body mass index; MAC, mid-upper arm circumference; FFM,
fat free mass; FFMI, fat free mass index; FM, fat mass; FMI, fat mass index; ECW,
tions were used with adjustments for age, sex, and baseline values
extracellular water; ICW, intracellular water; ICWI, intracellular water index; MNA,
for BW and MMSE. Two separate models were made in linear Mini nutritional assessment; MMSE,,Mini mental state examination; UPDRS III,
regression: one with change in BW and the other with change in FM Unified Parkinson disease rating scale motor score; SD, Standard deviation. P-value
as dependent variables. Both models were adjusted for sex, age and <0.05.
a
BW respectively FM at baseline and changes in the specific variable. PD n ¼ 57, Controls n ¼ 23.
b
PD n ¼ 55, Controls n ¼ 23.
B-value was presented as unstandardized coefficient. Multiple re- c
Controls n ¼ 20.
gressions analyses were used to further explore the correlations d
Controls n ¼ 23.
e
between changes in BW and FM and explanatory variables among Median (interquartiles).

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2013.12.012
 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8 5

Table 2 Table 3
Non-adjusted mean differences (D) in anthropometrics and assessments over three Bivariate correlations between body weight change and change in each variable over
years (mean
SD). P-value for Paired samples t-test. three years. Non-adjusted and partial correlation (adjusted).

(D) Variables PD (n ¼ 58) P Controls (n ¼ 24) P Pf (D) Variables Correlations

Anthropometry Non-adjusted Adjusteda

BW(kg) 1.62
4.60 0.009 0.23
3.08 0.724 0.177
PD Controls PD Controls
BMI (kg/m2) 0.74
1.76 0.002 0.23
0.91 0.219 0.092
Waist (cm)a 4.60
5.37 0.000 3.00
5.68 0.019 0.240 Anthropometry (n ¼ 58) (n ¼ 24) (n ¼ 52) (n ¼ 17)
Hip (cm)a 1.56
4.61 0.013 0.96
5.70 0.149 0.564 Waist (cm) 0.63** 0.48* 0.60** 0.55*
Waist/hip (ratio)a 0.03
0.05 0.000 0.02
0.05 0.036 0.376 Hip (cm) 0.72** 0.46* 0.72** 0.55*
Waist/height 0.03
0.03 0.000 0.02
0.03 0.011 0.257 Waist/hip (ratio) 0.10 0.28 0.03 0.34
(ratio)a Waist/height (ratio) 0.62** 0.43* 0.59** 0.50*
MAC (cm)b 0.71
1.45 0.000 0.22
0.94 0.279 0.078 MAC (cm) 0.49** 0.43* 0.53** 0.46
Calf circumference 0.05
1.44 0.809 0.26
1.30 0.345 0.379 Calf circumference (cm) 0.63** 0.43* 0.58** 0.34
(cm)c Total skinfold (mm) 0.76** 0.80** 0.76** 0.75**
Total skinfold 5.12
12.94 0.004 3.63
7.06 0.022 0.605 FFM (kg) 0.39** 0.33 0.31* 0.24
(mm)b FFMI (kg/m2) 0.39** 0.26 0.31* 0.17
Bioimpedanced FM (kg) 0.33* 0.57** 0.42* 0.49*
FFM (kg) 0.58
6.50 0.504 0.36
3.20 0.593 0.880 FMI (kg/m2) 0.33* 0.49* 0.42* 0.41
FFMI (kg/m2) 0.14
2.43 0.671 0.02
1.16 0.920 0.832 FM (%) 0.01 0.12 0.09 0.15
FM (kg) 2.16
6.35 0.013 0.58
3.67 0.457 0.267 ECW (l) 0.46** 0.37 0.41* 0.31
FMI (kg/m2) 0.86
2.40 0.009 0.25
1.15 0.301 0.247 ICW (l) 0.25 0.24 0.19 0.19
FM (%) 2.35
9.32 0.062 0.51
3.78 0.522 0.365 ECW/ICW (ratio) 0.21 0.15 0.15 0.15
ECW (l) 0.28
0.94 0.028 0.03
0.66 0.806 0.253 ICWI (l/m2) 0.25 0.21 0.18 0.17
ICW(l) 1.07
5.2 0.124 0.56
2.48 0.289 0.655 Diet
ECW/ICW (ratio) 0.05
0.16 0.019 0.03
0.11 0.299 0.429 Energy (Kcal) 0.18 0.32 0.12 0.13
ICVI (l/m2) 0.37
1.95 0.161 0.16
0.89 0.409 0.621 Protein (g) 0.30* 0.32 0.22 0.25
Assessments Fat (g) 0.19 0.43* 0.12 0.35
MNAe 0.07
2.44 0.830 0.65
1.66 0.095 0.327 Carbohydrates (g) 0.07 0.15 0.04 0.40
MMSEc 0.58
2.36 0.073 0.39
1.50 0.224 0.722 Assessments
MNA 0.25 0.42 0.18 0.12
BW, bodyweight; BMI, Body mass index; MAC, mid-upper arm circumference; FFM,
MMSE 0.11 0.04 0.08 0.06
fat free mass; FFMI, fat free mass index; FM, fat mass; FMI, fat mass index; ECW,
Hoehn & Yahrb 0.10 e 0.06 e
extracellular water; ICW, intracellular water; ICWI, intracellular water index; MNA,
UPDRS III 0.28* e 0.14 e
Mini nutritional assessment; MMSE, Mini mental state examination;; SD, Standard
Swallowingb,c 0.01 e 0.55 e
deviation. P-value <0.05.
a
PD n ¼ 57. BW, bodyweight; BMI, Body mass index; MAC, mid-upper arm circumference; FFM,
b
Controls n ¼ 23. fat free mass; FFMI, fat free mass index; FM, fat mass; FMI, fat mass index; ECW,
c
PD n ¼ 55 Controls n ¼ 23. extracellular water; ICW, intracellular water; ICWI, intracellular water index;
d
PD n ¼ 57 Controls n ¼ 23. MMSE, Mini mental state examination; UPDRS, Unified Parkinson disease rating
e
Controls n ¼ 20. scale.
f
Independent t-test, to test for differences in changes between PD patients vs. *P < 0.05 (2-tailed). **P < 0.01 (2-tailed).
controls. a
Adjusted for sex, age, baseline values for weight and MMSE.
b
Spearman coefficient.
c
postural instability and gait difficulty (PIGD) (n ¼ 31).25 The From UPDRS II.

remaining seven patients with characteristics in-between these

groups were included in the TD group. The proportion that gained
weight was similar in the TD and PIGD groups (56% vs. 61%). No
significant change over the three-year period was seen in global
cognition using the MMSE for patients and controls. A Wilcoxon
Signed Ranks test revealed no significant change in Hoehn and
Yahr, UPDRS III or UPDRS II swallowing score were revealed after
three years (Z ¼ 1.079, P ¼ 0.281; Z ¼ 1.130, P ¼ 0.259; Z ¼ 0.237,
P ¼ 0.813 respectively) and subsequently an unchanged median.
Patients treated with dopamine agonists with or without
(n ¼ 27 þ 6 ¼ 33) levodopa were compared with only levodopa
treated patients (n ¼ 24) by an independent two-tailed test. No
differences in BW (78.7
10.8 vs. 75.1
13.7; P ¼ 0.282) or in FM
(30.0
10.8 vs. 33.2
13.7; P ¼ 0.131) at three years were found.
PAL. This indicates that weight gain could be due to decreased
physical activity (Table 4). In controls, weight gain was associated
with an increase in carbohydrate energy percent (E%). With
changes in FM over three years as the dependent variable, an as-
sociation with increasing MMSE was discovered in PD patients. In
controls, gain in FM was negatively associated with a decrease in
dietary fat E%.
The multiple regression revealed an association between change
in BW and PAL (B ¼ 14.055, P ¼ 0.005) and UPDRS III (B ¼ 0.343,
P ¼ 0.032) (Table 5).
3.4. Reported energy intake, physical activity and MNA

3.2. Correlations between change in BW and anthropometric
variables
In the PD group, change in BW correlated with changes in all
anthropometric variables except waist/hip ratio: in the control
group, changes in BW correlated with increase in FM as revealed by
increases in waist and total skinfold thickness (Table 3).
3.3. Linear and multiple regressions
Linear regression with change in BW over three years as the
dependent variable revealed in PD patients an inverse relation with
Thirty-three per cent (n ¼ 19) of the PD patients and 26% (n ¼ 6)
of the controls lost BW during the recent three months before
baseline, according to MNA. Seventeen per cent (n ¼ 10) of the PD
patients and 21% (n ¼ 5) of the controls had lost BW at the follow up
after three years.
Fourteen per cent of the PD patients and none of the controls
were at risk of malnutrition (score 17e23.5 points) according to
MNA at baseline. At follow up 20.7% (n ¼ 12) PD patients and
8.3% (n ¼ 2) controls had a score between 17 and 23.5 points.
Neither PD patients nor controls were classified as malnourished
(score < 17) at baseline or at the 3-year follow-up, according to
MNA.

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
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6 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8

Table 4
Linear regression. Two separate models; one with change in body weight (D BW) and the other with change in fat mass (D FM) as dependent variables. Both models were
adjusted for sex, age and BW respectively FM at baseline and changes in the specific variable. B-value is presented as Unstandardized Coefficient.

(D) Variables D BW D FM
PD (n ¼ 57) Ctrl (n ¼ 23) PD (n ¼ 56) Ctrl (n ¼ 22)

B P B P B P B P

Energy, Kcal 0.001 0.395 0.001 0.673 0.000 0.742 0.001 0.722
Protein (g) 0.044 0.102 0.023 0.296 0.020 0.515 0.014 0.666
E% 0.167 0.302 0.131 0.376 0.131 0.484 0.063 0.775
Fat (g) 0.021 0.364 0.024 0.175 0.001 0.967 0.039 0.129
E% 0.087 0.291 0.103 0.064 0.106 0.266 0.168 0.031
CHO (g) 0.003 0.765 0.028 0.064 0.005 0.642 0.037 0.107
E% 0.089 0.215 0.118 0.051 0.064 0.439 0.140 0.109
PALa 8.554 0.025 0.481 0.903 0.291 0.953 3.203 0.522
MMSE 0.165 0.554 0.105 0.789 0.654 0.027 0.705 0.219
Hoehn & Yahr 0.393 0.692 e e 1.355 0.227 e e
UPDRS III 0.059 0.327 e e 0.021 0.744 e e
Swallowingb 0.496 0.658 e e 1.308 0.302 e e
LED 0.001 0.455 e e 0.000 0.902 e e
LEDc 0.001 0.570 e e 0.001 0.730 e e
d
L-dopa/agonists 0.399 0.800 e e 1.345 0.481 e e

CHO, carbohydrates; PAL, Physical activity level; MMSE, Mini mental state examination; UPDRS, Unified Parkinson disease rating scale; LED, levodopa equivalent dose: L-dopa,
levodopamine.
a
PD n ¼ 32, controls n ¼ 18.
b
From UPDRS II.
c
Medication at three years.
d
Two groups were compared; 1 ¼ L-dopa and 2 ¼ Agonists with our without L-dopa.

There were no differences in the reported EI or macronutrient association between change in BW and change in PAL (r ¼ 0.38;
intake between PD patients and controls at baseline or in changes P ¼ 0.027). The correlation was confirmed after adjustments
over three years in either group (Table 6). At three years, PD pa- (0.373; P ¼ 0.043, not in table) and by linear and the multiple
tients’ diets had a significantly higher carbohydrate E% compared to linear regression (Tables 5 and 6). There was no corresponding
controls (48.0 E% vs. 44.5 E%, P ¼ 0.034). A negative correlation association found among the controls.
between change in BW and change in amount of protein (g) was
found for patients (r ¼ 0.30; P ¼ 0.024), while BW change was
negatively associated with change in amount of fat (gram) in con- 4. Discussion
trols (r ¼ 0.43; P ¼ 0.037) (Table 3). The adjusted correlation
revealed no associations between change in BW and changes in the Three years after confirmed diagnosis, PD patients had gained
reported EI and macronutrients in PD patients or in controls weight and had an increased FM as measured by total skinfold and
(Table 3). BIS. The inverse relation between change in BW and change in PAL
A small but significant increase in PAL from baseline to three in patients indicates a lower level of physical activity. The preva-
years (1.54e1.62; P ¼ 0.035) was reported among the PD patients lence of weight gain did not differ between the motor phenotype
(n ¼ 33). There were no changes in reported PAL for controls (1.50e (PIGD or TD). In addition, no associations between weight gain and
1.54; P ¼ 0.376). Bivariate correlation revealed a negative medication calculated as LED at three years was found.
One could conceive that the degree of changes in motor
dysfunction is a determinant for changes in BW in early stages of
Table 5 PD. We found the adjusted correlation between BW and change in
Multiple regression analysis for PD patients (n ¼ 29). Change (D) in body weight UPDRS score not to be significant, while in the multiple regressions
(BW) and (D) in fat mass (FM) as dependent variables respectively. a weak but significant inverse relation was shown. However, due to
D BW D FM the design of the study the relation between changes in UPDRS
B P B P
motor scores and BW is difficult to evaluate since patients were
untreated at baseline while treated at three years. We cannot rule
Gender 0.508 0.770 3.624 0.116
out changes in motor function as a possible determinant for change
Age 0.000 0.997 0.252 0.204
BWa 0.109 0.251 e e in BW in PD patients when dopaminergic treatment is provided for
FMa e e 0.408 0.007 all the occasions to be compared.
LEDb 0.003 0.270 0.002 0.638 Increased waist circumference and waist/height ratio were
b,c
L-dopa vs. agonists 0.284 0.894 0.145 0.960 associated with the BW gain among PD patients in the present
(D) Variables
Energy (kcal) 0.003 0.080 0.001 0.712
study. Whether abdominal obesity predicts risk of cardiovascular
PAL 14.055 0.005 2.780 0.639 disease (CVD) is also of interest for assessing prognosis in PD.26
MMSE 0.164 0.695 0.836 0.121 Cereda et al. reported a low cardiometabolic risk in PD based on
Hoehn & Yahr 3.088 0.147 2.318 0.430 the number of risk factors in the metabolic syndrome, which in-
UPDRS III 0.343 0.032 0.004 0.982
cludes waist circumference. In addition, the same research group
LED, levodopa equivalent dose: L-dopa, levodopamine; PAL, Physical activity level; reported that visceral obesity predicted the development of de-
MMSE, Mini mental state evaluation; UPDRS, Unified Parkinson disease rating scale. mentia, indicating a need to include anthropometrics such as waist
a
at baseline.
b
at three years.
circumference in the prediction of disease progress.27 In an
c
Two groups were compared; 1 ¼ L-dopa and 2 ¼ Agonists with or without L- experimental model for studying PD, weight loss resulted in loss of
dopa. intra-abdominal fat.9

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
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 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8 7

Table 6 composition. The higher E% of carbohydrates and indication of

Energy and macronutrients at baseline and mean difference (D) at three-year decrease in protein in PD patients compared to controls at three
follow-up (mean
SD).
years could have contributed to the increased FM. Accumulation of
PD patients (n ¼ 58) Controls (n ¼ 24) fat for reasons other than simply explained by high-energy intake
Baseline (D) Baseline (D) Pa or low physical activity should be considered as patients reported
increased levels of physical activity although their EI did not
Energy
KJ 7787
2245 97
2029 7800
1985 320
1783 0.640 increase.
Kcal 1861
536 23
485 1864
475 77
426 0.638 Dopamine agonists may induce weight gain by encouraging
Protein compulsive eating and it has been reported that weight gain is
g 76.2
24.1 0.6
22.6 80.9
28.6 1.1
26.7 0.934
inhibited when dopamine agonist treatment is discontinued.30
E% 16.5
2.6 0.2
3.7 17.4
3.6 1.0
4.1 0.419
Fat When comparing BW and FM at three years in our population ac-
g 67.8
26.4 1.6
25.6 70.3
28.1 3.1
32.7 0.834 cording to dopamine agonists with or without levodopa vs. only
E% 32.1
6.6 0.3
7.1 33.5
7.7 0.7
9.8 0.609 levodopa treatment at three years, no differences were found. We
Carbohydrates used LED to assess if the total dopaminergic medication load could
g 219.9
56.9 1.2
60.4 207.3
53.1 5.4
40.8 0.714
have contributed to gain of BW and FM. No association was revealed
E% 48.0
7.3 0.0
8.3 45.0
8.3 0.5
9.0 0.819
between changes in BW or FM and LED, swallowing, Hoehn and
SD, Standard deviation; E%, Energy percent.
a Yahr and UPDRS III. Severity of motor symptoms (Hoehn and Yahr)
Independent T-test, non-adjusted p-value for the mean differences between PD
patients vs. controls over three years. and levodopa dose mg/kg/day have been shown to be associated
with nutritional risk.14 This study also reported that unintentional
weight loss is a strong marker for malnutrition.
In a study on a healthy elderly population, an interaction be- A limitation of the present study was the large number of
tween age and visceral obesity has been associated with cognition dropouts. The included 58 patients were younger and in better
and brain morphometry.28 We found no significant association health compared to the 87 patients excluded due to missing BW
between change in global cognitive performance using the MMSE data (of whom 30 had deceased). Such loss of data is difficult to
and BW change during the three-year investigation period. How- circumvent in prospective community-based studies of PD, which
ever, the linear regression revealed an association between change has a high proportion of participants in advanced age at baseline.
in FM and MMSE. Relations between cognitive function and The self-performed dietary and physical activity records may have
nutritional status are important to study further. been affected by both over- and underreporting due to gender, BW,
An increase in ECW/ICW ratio associated with weight gain can disease severity, and cognitive function, which was not adjusted
be a sign of relative loss of skeletal muscle mass (decrease in ICW, a for. The validated booklet (the Food Template) was an aid used to
proxy for skeletal muscle mass). The amount of ICW did not change assess portion sizes, but difficulties understanding how to complete
in the present study, indicating an unaltered amount of skeletal the food diary and physical activity log could affect the quality of
muscle mass. However, the ratio ICW/FFM significantly decreased data. The main strengths of the present study are the community-
in patients, a finding that indicated a changed composition of the based prospective study design and the several and extensive
FFM. In addition to loss of FFM, sarcopenic obesity indicates an evaluations made of PD patients and controls, design features that
increase in FM despite normal or high body weight. Findings in allowed the investigation of multiple aspects of the disease over
other studies on the development of sarcopenic obesity in time.
connection with weight gain during chronic disease could be In conclusion, PD patients gained BW and FM after three years,
applicable as a health risk for patients with PD.29 manifested by an increase in waist size, waist/height ratio, and total
To appraise effects of nutritional status on disease progression, skin fold. Despite an increase in PAL overtime it was revealed that
energy balance ought to be included in an evaluation of changes in PAL was inversely related to weight gain. No associations were
body composition. The weight gain reported in the present study found between weight gain and EI. We continue to follow this study
was not associated with increased EI as this did not change from population to assess nutritional status in more advanced disease
baseline to follow-up. Theoretically, an increase in EI could have stages. We may gain knowledge at what stage in the disease major
occurred during the years preceding diagnosis leading to an on- nutritional problems and malnutrition (including weight loss)
going increase in BW. Although we have no data to refute or sup- mainly occur, information that could provide guidance to when
port this possibility, almost identical BW in patients and controls at dietary advice and intervention are particularly important for PD
baseline suggests that no change in BW had occurred previous to patients.
the study’s start date. However, 32.8% reported loss of weight prior
to diagnosis (from MNA). Could the increase in BW be related to a Statement of authorship
decrease in physical activity? In 57% of the patients (n ¼ 33) who
completed the activity registration, change in BW was negatively Study concept and design: MV, LH; Acquisition of data: LH;
correlated with PAL, confirmed by the linear and multiple regres- Analysis and interpretation of data: MV, LH; Drafting and/or critical
sion analysis. Thus a lower level of activity could have contributed revision of the manuscript: MV, LH, LF, MC, JL; Statistical analysis:
to weight gain. MV. All authors read and approved the final manuscript.
Weight gain was associated with a decrease in protein intake
among PD patients, before adjusting for confounding. This finding Funding sources
is important, as protein sources provide several important nutri-
ents (e.g., vitamin B12, phosphate, magnesium, and iron) needed for This work was supported by grants from The Swedish Medical
people suffering chronic diseases. The nutrient density of the diet Research Council, The Swedish Parkinson Foundation (Svenska
reported in a subgroup of the present population at baseline was Parkinsonstiftelsen) and Västerbotten County Council (ALF).
associated with olfactory function, age, and low levels of protein,
phosphate, and folic acid were associated with smell distur- Conflict of interest statement
bances.13 The quality of diet, rather than the total energy intake,
might have influenced weight change and changes in body The authors had no conflict of interest to declare.

Please cite this article in press as: Vikdahl M, et al., Weight gain and increased central obesity in the early phase of Parkinson’s disease, Clinical
Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2013.12.012
8 M. Vikdahl et al. / Clinical Nutrition xxx (2014) 1e8
Acknowledgement
Lennart Bäckman and Birgitta Törnkvist has contributed with
valuable advice concerning the statistical analyses.
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