The Association of Stress and Resilience with Non-Motor Symptoms and Quality of Life in Parkinson's Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that affects approximately 1% of persons over the age of 65. (1) PD is characterised by alpha-synuclein-immunoreactive inclusions, or Lewy bodies, that cause neuronal cell death in monoaminergic and cholinergic neurons. (2, 3) While the majority of cell death occurs in the basal ganglia, cotico-striato-thalamo-cortical loops allow widespread areas of the brain to also be affected. (4) However, by the time motor symptoms first appear, 50 to 60% of niagral neurons and 70 to 80% of dopamine levels in the caudate nucleus have degenerated. (5, 6) PD is predominantly characterised as a motor disease, with its diagnosis dependent on the presence of cardinal motor symptoms, including bradykinesia, muscular rigidity, resting tremor and postural instability. (7) Non-motor symptoms (NMS) are also widely prevalent in PD, with almost all persons with PD experiencing at least one, however they are often under-recognised and under-treated. (8, 9) The most frequently reported NMS are fatigue and anxiety, however they can include other neuropsychiatric symptoms, sleep disorders, autonomic symptoms and sensory symptoms. (8) Furthermore, NMS have been shown to impact quality of life (QoL) more than motor symptoms, with apathy, attention difficulties, fatigue, psychiatric symptoms and memory all shown to have a negative association with QoL. (9) Stress is a natural, short-lived response to benefit the individual in the stressful situation. (10) Stress works through two primary mechanisms, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary. (11, 12) However chronic exposure to stress can lead to General Adaptation Syndrome, which can have detrimental impacts to an individual’s health. (10) This can be due to negative states, often leading to poor health practices, and overexposure to stress hormones such as cortisol, which can have effects on hippocampal volume and permanent atrophy. (13-15) Resilient individuals are better able to deal with stress as they have the ability to adapt to change while maintaining their relationships and state of system. (16) This is particularly relevant in chronic diseases such as PD due to the daily variability of the disease. (17) This present study examines the relationships between NMS and QoL in PD with both stress and resilience. The intentions of this study were to: 1. Identify the burden of perceived stress on both frequency and severity of NMS in PD by total score, domains and individual symptoms, with a particular focus on mood disorders; 2. Identify the burden of perceived stress on QoL in PD as a total, by dimension and individual symptom; 3. Identify the benefit of resilience on both frequency and severity of NMS of PD by total score, domains and individual symptoms, with a particular focus on mood disorders; 4. Identify the benefit of resilience on QoL in PD as a total, by dimension and individual symptom. From the aims, the following hypotheses were developed: 1. There will be a positive association between high perceived stress and increased frequency and severity of NMS, including mood disorders such as anxiety and depression; 2. There will be a negative association between high perceived stress and QoL in PD; 3. There will be a negative association between high resilience and increased frequency and severity of NMS, including mood disorders such as anxiety and depression; 4. There will be a positive association between high resilience and high QoL in PD. This study used a cross-sectional design. Persons with idiopathic PD were recruited primarily through PD support groups and word of mouth. One hundred and four persons were recruited in South East Queensland, with 100 meeting inclusion criteria. Participants were guided through a number of instruments and a proforma, conducted by both the examiner and self-performed. Descriptive and multivariate analysis was performed to analyse the data collected, namely Person’s Correlation and Mann-Whitney U Test. Descriptive analysis showed over half of the participants were male, and a large majority were Caucasian. Three quarters of participants had a carer present during the study, and three quarters were also referred to the study through Parkinson’s Queensland Incorporated. The average age of participants was 69.1 years, and average age of diagnosis was 62.38 years. The mean Hoehn and Yahr (HY) Stage 2.35, and mean Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score of 30.68. Results found a positive significant relationship between perceived stress and NMS, in both their overall score, severity and frequency. The domain and individual symptoms that showed the strongest associations belonged to the mood/cognition domain. In particular, depression and anhedonia showed the strongest relationships with stress. In regards to mood disorders, both anxiety and depression showed significant positive associations with perceived stress, with persons who classified as depressed and anxious having significant higher stress scores than those who were not. Stress was inversely associated with QoL, with an association of p<0.001 with all bar one QoL dimensions. Significant inverse associations also existed with 36 of the 39 QoL questions, and 34 QoL complaints showed significantly higher stress scores for persons who had experienced the symptom compared to those who had not. Results also showed a negative significant relationship between resilience and NMS, in both their overall score, severity and frequency. Much like perceived stress, the mood/cognition domain showed the strongest associations for both the domain and individual symptoms. Anhedonia was the NMS with the strongest relationship with resilience. Anxiety and depression also showed inverse associations with resilience, and there was a significant difference in resilience between those who were anxious and depressed and those who were not. QoL was also inversely significantly associated with resilience, all dimensions being significantly associated. Emotional well-being dimension and the pertaining QoL complaints had the strongest associations, closely followed by the communications dimension. The results of this study suggest that NMS and QoL in PD are closely related to both stress and resilience. It highlights that stress has greater association with PD symptomology, which could be due to a combination of the stress response affecting NMS, or PD itself increasing stress through its pathophysiology. In particular, this study highlighted the relationship between stress and resilience with mood and cognition issues in PD, which have an impact on QoL. The nature of these relationships however is unclear, with the direction of causality not yet determined. However, it is highly likely that a network causality is present. It is important to further study these relationships, as stress reduction mechanisms and harnessing resilience may improve NMS management and enhance QoL.