Abstract
Nonmotor symptoms (NMS) in Parkinson's disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson's Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson's progressed. In conclusion, males experienced increased NMS burden in Parkinson's disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients' quality of life by therapeutically alleviating nonmotor symptoms.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder clinically associated with three cardinal symptoms– bradykinesia, rigidity, and rest tremor
Our analyses included a total of 811 subjects in three cohorts: 241 healthy controls (HC), 489 Parkinson’s disease subjects (PD), and 81 subjects without evidence of dopaminergic deficit (SWEDD)
We discovered that PD patients reported a higher degree of nonmotor symptoms (NMS) abnormalities on almost all nonmotor scales measured, and sex of the patient had a strong influence on NMS progression
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder clinically associated with three cardinal symptoms– bradykinesia, rigidity, and rest tremor. Understanding the characteristics and patterns of NMS is valuable from a therapeutic point of view, and it may provide clues to the incipient site of PD pathology In this pursuit, we aimed to characterize NMS in Parkinson’s disease. Previous attempts have been made to study NMS based on motor laterality [6,7,8,9,10], sex [11,12,13,14,15,16,17,18,19], and handedness [4, 20,21,22,23] Most of these studies evaluated NMS only at onset and sample sizes were not large enough resulting in conflicting conclusions
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