Predictors of stress resilience in Parkinson’s disease and associations with symptom progression

van der Heide, Anouk; Dommershuijsen, Lisanne J.; Puhlmann, Lara M. C.; Kalisch, Raffael; Bloem, Bastiaan R.; Speckens, Anne E. M.; Helmich, Rick C.

doi:10.1038/s41531-024-00692-4

Cited by 6 publications

(2 citation statements)

References 59 publications

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“…These differences can be explained by the lack of large-scale, multi-sampled, circadian studies up until today and variable inclusion criteria, including age, drug treatment and disease stage [ 12 ]. Interestingly, the COVID-19 pandemic, considered as an environmental stressor, did not accelerate PD progression, but exacerbated depressive symptoms in stressor-reactive (vs. stressor-resilient) PD patients [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration

Nakos Bimpos,

Karali,

Antoniou

et al. 2024

acta neuropathol commun

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A link between chronic stress and Parkinson’s disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.

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Section: Discussionmentioning

confidence: 99%

Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration

Nakos Bimpos,

Karali,

Antoniou

et al. 2024

acta neuropathol commun

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“…Positive appraisal style, the tendency to appraise potentially threatening situations in a positive way, has been proposed to be an important resilience mechanism, and therefore offers a potential target for stress-alleviating approaches [ 39 ]. The Positive Appraisal Style Scale (PASS) , based on the German 14 item PASS-process described by Petri-Romao and colleagues [ 40 ] will be used to measure positive appraisal style.…”

Section: Methods: Participants Interventions Randomization Procedures...mentioning

confidence: 99%

Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson’s disease

van der Heide,

Goltz,

de Vries

et al. 2024

BMC Neurol

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Background People with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD. Methods In a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression. Discussion MIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future. Trial registration ClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.

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Experiences of Living With the Nonmotor Symptoms of Parkinson's Disease: A Photovoice Study

Smith,

Callis,

Bridger‐Smart

et al. 2024

Health Expectations

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BackgroundNonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these remain poorly understood with suboptimal clinical management. These unmet needs are an important determinant of health‐related quality of life (QoL) in PD.ObjectiveThe aim of this study was to gain insights into the experience of living with the NMS of PD in real‐time using participatory action methodology.MethodUsing the photovoice method, 14 people with PD took photographs to document their experiences of living with the NMS of PD. They composed corresponding written narratives to capture the impact of NMS on their daily activities and QoL. In total, 152 photographs and corresponding narratives were analysed using thematic analysis with an inductive approach.ResultsFour interrelated themes were identified. Emotional well‐being and sense of self encompassed a process of adjustment to living with PD. Engaging in valued activities, adopting a positive mindset and utilising coping strategies were thought to enhance confidence and self‐esteem. Social support and societal awareness highlighted the importance of supportive relationships and socialising to aid participation and avoid isolation. Barriers to social engagement included the unpredictability of NMS and nonvisible NMS being neglected or misunderstood.ConclusionFindings demonstrated the far‐reaching impact of nonmotor aspects of PD on emotional, occupational and social dimensions. These needs could be addressed through person‐centred and comprehensive approaches to care.Patient or Public ContributionThis study utilised a participatory research approach allowing participants to choose the subjects that mattered to them and how to present their results. Additionally, a group workshop was held with people with PD, their family members and healthcare professionals to guide theme development.

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Predictors of stress resilience in Parkinson’s disease and associations with symptom progression

Cited by 6 publications

References 59 publications

Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration

Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration

Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson’s disease

Experiences of Living With the Nonmotor Symptoms of Parkinson's Disease: A Photovoice Study

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