Weight Loss Over 5 Years Linked to Faster Parkinson’s Progression

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Fluctuations in weight, either a loss or a gain, occurred significantly more often in people with Parkinson’s disease than in those without the progressive neurodegenerative disorder, a study has found.

Weight loss in Parkinson’s patients was associated with a faster progression of motor and cognitive declines over a five-year period. Conversely, weight gain over that same time period was linked to a slower progression of motor symptoms.

Certain biomarkers, including amyloid burden, blood urate — antioxidant — levels, and brain imaging of dopamine, might serve as predictors of future weight fluctuations, data showed.

“In this longitudinal study, we found that weight loss was associated with poor clinical outcomes … while a more favourable progression of motor function was observed in patients with weight gain,” the researchers wrote.

The study, “Clinical trajectories and biomarkers for weight variability in early Parkinson’s disease,” was published in Nature Portfolio Journal – Parkinson’s Disease.

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Weight changes common in Parkinson’s

Weight variability — including unintended weight loss and gain — is a relatively common non-motor symptom of Parkinson’s that has been reported across all disease stages.

Such weight fluctuations could be related to a multitude of factors. These include medications, lack of appetite, swallowing difficulties, gastrointestinal problems, alterations in hormones involved in appetite, or brain changes that influence eating behaviors.

But the mechanisms underlying unintended weight changes in Parkinson’s are not well-understood, nor is the relationship between weight changes and other clinical outcomes.

“The lack of a clear pathophysiological understanding is accompanied by the scarcity of biomarkers for this complex clinical condition,” the researchers wrote. In other words, a lack of pathophysiology — a pairing of disease pathology or development with the functional changes that accompany it — makes it hard for clinicians to reach a clear prognosis for Parkinson’s patients.

In this study, researchers examined weight variability and its association with clinical trajectories and disease biomarkers over five years in Parkinson’s patients and healthy volunteers involved in the Parkinson’s Progression Marker Initiative (PPMI). The PPMI, launched by The Michael J. Fox Foundation for Parkinson’s Research in 2010, seeks to identify biomarkers of the disease’s onset and progression.

Included in the analysis were 405 Parkinson’s patients — 64.7% of them men — with a mean age of 61.5. The study also involved 187 healthy participants — 65.4% of whom were men — with a mean age of 61.1; these individuals served as controls.

The data showed that Parkinson’s patients had higher weight variability compared with healthy controls. Among patients, 203 were considered to have stable weight, whereas 134 were “weight losers” and 68 were “weight gainers.”

Patients in the weight loss group experienced more difficulties in activities of daily living at the study’s start (baseline) compared with weight-stable patients.

They also had higher levels in the cerebrospinal fluid — the fluid surrounding the brain and spinal cord — of amyloid-beta, a biomarker of disease progression in Alzheimer’s disease which has more recently been seen in Parkinson’s patients.

Over the course of follow-up, weight loss patients experienced a faster progression of overall disease severity, as measured by the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score. Weight losers also saw greater impairments in motor experiences of daily living, as measured by the MDS-UPDRS Part II, compared with stable patients.

Activities of daily living and cognition also showed faster declines in the weight loss group.

In contrast, patients who gained weight showed a slower progression of motor symptoms, reflected by MDS-UPDRS Part III scores.

“We confirm that weight variability may have a critical clinical significance in [Parkinson’s], with weight loss as a driver of poor outcomes, and weight gain associated with slower motor progression in the long term,” the researchers wrote.

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Biomarkers for weight variability

Binge eating disorder — marked by frequently eating unusually large amounts of food and out-of-control feeding behaviors — was more prevalent in weight gain patients. Across all patients, treatment with dopamine agonists, a common Parkinson’s therapy, was associated with binge eating.

Blood levels of urate also were measured as a potential biomarker for weight variability. Urate is an antioxidant that has been linked to a decreased risk of Parkinson’s and slower disease progression.

Those who gained weight had higher urate levels compared with the stable group, and those who lost weight had lower levels.

A brain region called the striatum has been implicated in maintaining calorie requirements through dopamine, which is the neurochemical that’s lost in Parkinson’s. In this disorder, the nerve cells that normally project to the striatum and supply it with dopamine degenerate.

Using brain imaging, the researchers examined a proxy measure of this loss of dopamine (denervation).

Results showed that striatal denervation on the right side of the brain, but not the left, at baseline was predictive of weight variability in both patients and healthy participants.

Based on these findings, the researchers proposed that “dopaminergic imaging and urate levels may serve as a predictor of weight variability in [Parkinson’s].”

Certain clinical variables, such as diet, bowel function, and exercise, which could have influenced the findings, were not available for analysis, the team noted.

Additional long-term studies will be needed  “to improve the characterization and the identification of biomarkers of weight variability in [Parkinson’s],” they wrote.

Such studies should include nutritional assessments and measurements of body composition (i.e. fat and muscle), the researchers also noted.

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