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[Preprint]. 2023 Dec 22:rs.3.rs-3683455.
doi: 10.21203/rs.3.rs-3683455/v1.

Health phenome of Parkinson's patients reveals prominent mood-sleep cluster

Abby Olsen  1 , Joseph Locascio  2 , Idil Tuncali  3 , Nada Laroussi  3 , Elena Abatzis  3 , Polina Kamenskaya  3 , Yuliya Kuras  3 , Tom Yi  3 , Aleks Videnovic  4 , Michael Hayes  3 , Gary Ho  3 , Jordan Paulson  3 , Vikram Khurana  3 , Todd Herrington  4 , Bradley Hyman  4 , Dennis Selkoe  3 , John Growdon  4 , Stephen Gomperts  4 , Trond Riise  5 , Michael Schwarzschild  6 , Albert Hung  3 , Anne Wills  4 , Clemens Scherzer  3
Affiliations

Health phenome of Parkinson's patients reveals prominent mood-sleep cluster

Abby Olsen et al. Res Sq. .

Abstract

Background: Associations between phenotypic traits, environmental exposures, and Parkinson's disease have largely been evaluated one-by-one, piecemeal, and pre-selections. A comprehensive picture of comorbidities, phenotypes, exposures, and polypharmacy characterizing the complexity and heterogeneity of real-world patients presenting to academic movement disorders clinics in the US is missing.

Objectives: To portrait the complexity of features associated with patients with Parkinson's disease in a study of 933 cases and 291 controls enrolled in the Harvard Biomarkers Study.

Methods: The primary analysis evaluated 64 health features for associations with Parkinson's using logistic regression adjusting for age and sex. We adjusted for multiple testing using the false discovery rate (FDR) with £ 0.05 indicating statistical significance. Exploratory analyses examined feature correlation clusters and feature combinations.

Results: Depression (OR = 3.11, 95% CI 2.1 to 4.71), anxiety (OR = 3.31, 95% CI 2.01-5.75), sleep apnea (OR 2.58, 95% CI 1.47-4.92), and restless leg syndrome (RLS; OR 4.12, 95% CI 1.81-12.1) were significantly more common in patients with Parkinson's than in controls adjusting for age and sex with FDR £ 0.05. The prevalence of depression, anxiety, sleep apnea, and RLS were correlated, and these diseases formed part of a larger cluster of mood traits and sleep traits linked to PD. Exposures to pesticides (OR 1.87, 95% CI 1.37-2.6), head trauma (OR 2.33, 95% CI 1.51-3.73), and smoking (OR 0.57, 95% CI 0.43-0.75) were significantly associated with the disease consistent with previous studies. Vitamin supplementation with cholecalciferol (OR 2.18, 95% CI 1.4-3.45) and coenzyme Q10 (OR 2.98, 95% CI 1.89-4.92) was more commonly used by patients than controls. Cumulatively, 43% (398 of 933) of Parkinson's patients had at least one psychiatric or sleep disorder, compared to 21% (60 of 291) of healthy controls.

Conclusions: 43% of Parkinson's patients seen at Harvard-affiliated teaching hospitals have depression, anxiety, and disordered sleep. This syndromic cluster of mood and sleep traits may be pathophysiologically linked and clinically important.

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Conflict of interest statement

CRS is named as co-inventor on a US patent application on sphingolipids biomarkers that is jointly held by Brigham & Women’s Hospital and Sanofi. CRS has consulted for Sanofi Inc. and Calico; has collaborated with Pfizer, Opko, and Proteome Sciences, Genzyme Inc., and Lysosomal Therapies; is on the Scientific Advisory Board of the American Parkinson Disease Association; has served as Advisor to the Michael J. Fox Foundation, NIH, Department of Defense, and Google; has received funding from the NIH, the U.S. Department of Defense, the Michael J. Fox Foundation, and the American Parkinson Disease Association.

Figures

Figure 1
Figure 1
Results of logistic regression. Depression, anxiety, restless leg syndrome, sleep apnea, vitamin D supplementation, coenzyme Q-10 supplementation, head trauma, and exposure to pesticides were over-represented in PD. Smoking was inversely associated with PD. Odds ratio with 95% confidence limit for each variable is shown.
Figure 2
Figure 2
Heat map demonstrating correlations between the individual clinical and environmental variables. A. Pearson correlation matrix. B. Several sets of variables are positively correlated, forming clusters of biologically related phenomena. The largest clusters in our dataset include a linked sleep and psychiatric factor cluster, a metabolic syndrome cluster, and a vitamin use cluster. P-values indicating the significance of the correlation are shown in the boxes. C. Of the 3 clusters, only the sleep-mood cluster is significantly associated with PD.
Figure 3
Figure 3
High prevalence of sleep and mood disorders in PD patients. A. PD patients are more likely than healthy controls to have multiple sleep and mood disorders. B. Among PD patients with multiple sleep and mood depression, a large majority have depression.
Figure 4
Figure 4
Schematic demonstrating the variables examined in this study. Variables span domains of past medical history, medication and supplement use, social history, and environmental exposures. They capture functions of many organ systems. Variables that were significant in the logistic regression are indicated with *.
See this image and copyright information in PMC

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