Progressive and accelerated weight and body fat loss in Parkinson's disease: A three-year prospective longitudinal study

https://doi.org/10.1016/j.parkreldis.2020.06.015Get rights and content

Highlights

  • 42% of patients with Parkinson's disease had significant weight loss over 3 years.

  • Patients had greater reductions in body fat (including visceral fat) vs. controls.

  • There were no between-group differences in the change in muscle mass parameters.

  • Worsening psychosis was associated with weight loss in PD.

  • Constipation severity and worsening dyskinesia were associated with fat loss in PD.

Abstract

Introduction

Although weight loss is common in Parkinson's disease (PD), longitudinal studies assessing weight and body composition changes are limited.

Methods

In this three-year longitudinal study, 125 subjects (77 PD patients and 48 spousal/sibling controls) underwent clinical, biochemical and body composition assessments using dual-energy X-ray absorptiometry.

Results

Patients were older than controls (65.6 ± 8.9 vs. 62.6 ± 7.1, P = 0.049), with no significant differences in gender, comorbidities, dietary intake and physical activity. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases (6.5 to 13.0%) classified as underweight at study end. Over three years, patients demonstrated greater reductions in BMI (mean −1.2 kg/m2, 95%CI-2.0 to −0.4), whole-body fat percentage (−2.5% points, 95%CI-3.9 to −1.0), fat mass index (FMI) (−0.9 kg/m2, 95%CI-1.4 to −0.4), visceral fat mass (−0.1 kg, 95%CI-0.2 to 0.0), and subcutaneous fat mass (−1.9 kg, 95%CI-3.4 to −0.5) than in controls, with significant group-by-time interactions after adjusting for age and gender. Notably, 31.2% and 53.3% of patients had FMI<3rd (severe fat deficit) and <10th centiles, respectively. Muscle mass indices decreased over time in both groups, without significant group-by-time interactions. Multiple linear regression models showed that loss of body weight and fat mass in patients were associated with age, dyskinesia, psychosis and constipation.

Conclusions

We found progressive loss of weight in PD patients, with greater loss of both visceral and subcutaneous fat, but not muscle, compared to controls. Several associated factors (motor and non-motor disease features) were identified for these changes, providing insights on possible mechanisms and therapeutic targets.

Introduction

Unintended weight loss is highly prevalent in PD [1], sometimes preceding diagnosis and often becoming pronounced over the disease course [2,3]. The literature so far suggests that it manifests primarily from mid-stages of the disease [[2], [3], [4]]. Importantly, weight loss is associated with negative outcomes including worse quality of life, more severe parkinsonism, osteoporosis and fractures, pressure ulceration, dementia, dependency, and death [1,[3], [4], [5], [6], [7], [8]]. The condition is challenging to manage, given that underlying etiological factors are poorly understood. Contributing factors include gastrointestinal dysfunction (e.g., nausea, anorexia, and dysphagia), hyposmia, depression, altered reward processing, psychosis, cognitive impairment, loss of functional ability (e.g., preparing meals or self-feeding), increased energy expenditure due to muscular rigidity or involuntary movements, pain, and treatment-related factors; disruption of complex interactions between hypothalamic and peripheral mechanisms of feeding regulation also play an important role [[5], [6], [7], [8], [9], [10]].

Body weight and composition are known to change with age, generally with reductions in body weight and skeletal muscle and bone mass, but increases in fat, especially visceral fat [11,12]. Preliminary research suggested that weight loss in PD may predominantly be due to fat rather than muscle loss [6,13]. However, most studies on body composition in PD have been limited by small sample sizes, lack of clinical correlation, and cross-sectional design providing limited insight into the temporal evolution of body composition alterations in PD [[13], [14], [15], [16], [17], [18]]. To our knowledge, only three small studies evaluated body composition changes using a longitudinal design, with conflicting results. Patients were recruited at different disease phases, followed for variable periods (1–3 years), and studied using bioelectrical impedance (BIA) (n = 58) or more precise body imaging methods, i.e. dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (n = 25–26) [[15], [16], [17]].

Our objectives were to: (1) describe the changes in body weight and composition in a consecutively-recruited cohort of patients over a three-year period, and compare these with non-PD spousal/sibling controls; and (2) determine the factors associated with body weight and composition alterations in PD.

Section snippets

Subjects

Patients and corresponding controls from a previous cross-sectional study in 2015 [13] were invited to return for repeat assessments three years later, in 2018. Inclusion and exclusion criteria for patients and controls were as previously described [13]. Briefly, patients fulfilling standard clinical diagnostic criteria for PD and able to reliably complete study assessments were consecutively recruited. Two patients on apomorphine infusion who were not included in the 2015 report were included

Patient characteristics and study flow

Patient flow is depicted in Supplementary Fig. 1. There were 95 patients at baseline, of whom 77 completed three-year follow-up. Reasons for dropout were deaths (n = 9, i.e., 6/37 = 16% of those with FMI<10th centile at baseline and 3/58 = 5.2% of those with FMI≥10th centile at baseline), severe disability (n = 3), diagnosis reassigned (to progressive supranuclear palsy; n = 2) and treatment with deep brain stimulation (DBS) (n = 4; these patients were excluded due to the well-recognized

Discussion

In this three-year longitudinal prospective study, patients with primarily moderately-advanced PD showed progressive and greater loss of body weight and fat (in both visceral and subcutaneous compartments), but not of muscle mass, compared to non-PD controls. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases classified as underweight (BMI<18.5 kg/m2) in 2018. Notably, at three years, nearly one-third and more than one-half

Funding sources

This work was supported by the University of Malaya Faculty Research Grant (GPF018C-2018) and University of Malaya Parkinson's Disease and Movement Disorder Research Program (PV035-2017). These funding sources had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Authors’ contribution

Conception and design of the study: AH Tan, SY Lim, M Grossmann, NM Ramli.

Acquisition of data: VW Yong, YJ Tan, YD Ng, XY Choo, K Sugumaran, AH Tan.

Analysis and interpretation of data: AH Tan, VW Yong, SY Lim, K Chinna, MNM Shah, RRAR Aman, NM Ramli, M Grossmann, FM Moy.

Drafting of manuscript: VW Yong, SY Lim, AH Tan.

Revising the manuscript for intellectual content: AH Tan, SY Lim, M Grossmann, K Chinna, NM Ramli, MNM Shah, RRAR Aman, FM Moy, YJ Tan, YD Ng, XY Choo, K Sugumaran.

Final approval

Declaration of competing interest

None.

Acknowledgement

The authors are grateful to the patients with Parkinson's disease at the University of Malaya and their caregivers, for their participation in this research. We also gratefully acknowledge the late Mdm. Ooi Geok Tuan, and her family, for a donation that helped to support Dr. Voon Wei Yong's postgraduate (Master of Medical Science) studies.

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