Living with the Unknown: Intolerance of Uncertainty in Parkinson's Disease

Abstract

Background

Parkinson's disease (PD) is marked by pervasive uncertainty due to fluctuating motor and non‐motor symptoms, variable treatment response, and an unpredictable clinical course. Intolerance of uncertainty (IU), a tendency to perceive ambiguity as threatening and respond with worry, avoidance, or decisional paralysis, may be consequential in PD, yet lacks a PD‐focused synthesis.

Objective

To synthesize conceptual, qualitative, and emerging quantitative literature on IU in idiopathic PD, describe clinical and psychosocial correlates across the illness trajectory, and identify implications for assessment and intervention.

Methods

This targeted narrative review searched MEDLINE (PubMed), Embase, PsycINFO, and Web of Science from inception to May 22, 2025, supplemented by reference screening and Parkinson's disease conference or guidance sources. English‐language empirical and clinically informative papers addressing intolerance of uncertainty (IU) or closely related uncertainty constructs in adults with idiopathic PD and/or care partners were appraised at title/abstract and full‐text levels, then charted for narrative synthesis.

Results

Across qualitative, quantitative, intervention, and clinical review/guidance papers, symptom unpredictability, treatment uncertainty, identity disruption, shame, and future‐planning concerns were linked with anxiety, demoralization, avoidance, reduced participation, and poorer quality of life.

Conclusion

IU may be a modifiable, common underlying pathway through which PD‐related unpredictability, potentially influenced by dopaminergic, executive, and stress‐system vulnerabilities, contributes to sustained psychological and functional burden. Advancing PD‐sensitive measurement and testing IU‐targeted interventions within multidisciplinary care models may improve adjustment and quality of life for patients and caregivers.

Uncertainty is a defining feature of human life, but in the context of chronic illness, it is a distressing daily reality. Intolerance of uncertainty (IU) refers to the dispositional tendency to appraise ambiguous situations as threatening and to respond with heightened anxiety, worry, or avoidance. Carleton ¹ describes IU as “an individual's dispositional incapacity to endure the aversive response triggered by the perceived absence of salient, key, or sufficient information, and is sustained by the associated perception of uncertainty” (p. 31). Originally conceptualized within models of worry and anxiety, ² IU is now recognized as a transdiagnostic factor across mood, anxiety, and obsessive‐compulsive disorders. Individuals high in IU often exhibit greater emotional reactivity, impaired decision‐making, and difficulties with adaptive coping, all of which contribute to diminished well‐being. ³ , ⁴

Beyond psychiatric disorders, IU has emerged as an important construct in the context of chronic medical conditions characterized by unpredictable symptoms and uncertain prognoses, including cancer, multiple sclerosis, and chronic pain. In these contexts, higher IU is associated with greater emotional distress, maladaptive coping strategies, reduced adherence to medical care, avoidance of health information, and difficulty engaging in long‐term planning. ⁵ , ⁶ This underscores IU as a psychological mechanism shaping mental health outcomes and the lived experience of chronic illness.

This framework is particularly relevant to Parkinson's disease (PD), a progressive neurodegenerative disorder affecting more than eight million people worldwide. ⁷ While PD is classically defined by its motor symptoms, tremor, rigidity, bradykinesia, and postural instability, it also involves non‐motor features, including anxiety, depression, fatigue, and cognitive changes. ⁸ Anxiety affects up to 50% of people with PD (PWP) and is linked to poorer health‐related quality of life. ⁹ Despite its prevalence, mechanisms driving anxiety in PD remain underexplored, limiting the development of tailored interventions.

PD's daily realities are permeated with uncertainty throughout the disease course. From the day of diagnosis and even during the prodromal period and for those at‐risk, patients face unpredictability in medication effectiveness, motor “on–off” fluctuations, dyskinesias, and disease trajectory. Brown and colleagues ¹⁰ found that metacognitive factors like IU exacerbate anxiety and distress associated with motor fluctuations, suggesting that IU intensifies the psychological burden of these unpredictable experiences. Thus, IU may explain why some individuals easily adapt to PD with resilience, while others experience substantial distress and functional impairment and may benefit from additional support to build resilience.

Methods

Search Strategy and Study Identification

We conducted a targeted literature search in MEDLINE (via PubMed), Embase, PsycINFO, and Web of Science from database inception through May 22, 2025. Search strategies paired Parkinson's disease terms (“Parkinson*” OR “parkinsonism”) with IU‐relevant terms (eg, “intolerance of uncertainty,” “uncertainty intolerance,” “uncertainty distress,” “fear of the unknown”), using both controlled vocabulary and keyword variants. Because terminology is inconsistently applied in the PD literature, we retained records indexed under broader uncertainty or metacognitive terms when the focal construct aligned with contemporary definitions of IU. We also screened reference lists of included papers and reviewed relevant conference proceedings and clinical guidance documents to identify additional eligible reports.

Eligibility Criteria

We included peer‐reviewed, English‐language empirical studies (quantitative, qualitative, or mixed‐methods) and conceptual papers that examined IU (or closely related constructs, such as uncertainty distress) in adults with idiopathic PD and/or care partners. Eligible papers contributed original data, psychometric evaluation of IU measures, or a substantive theoretical analysis with clear clinical relevance. We excluded studies focused solely on pediatric parkinsonism, atypical Parkinsonism, or other neurologic conditions unless PD–specific findings were reported separately.

Synthesis of Evidence

Given the small and methodologically heterogeneous PD‐specific literature, and the frequent use of constructs adjacent to rather than directly measuring intolerance of uncertainty (IU), we used a thematic narrative synthesis intended to move from lived experience to explanatory pathways and then to clinical application. Rather than treating conceptual, psychosocial, and translational issues as discrete silos, we organized the evidence into six interrelated domains: (i) how uncertainty manifests across the PD trajectory; (ii) psychosocial and participation consequences of uncertainty; (iii) caregiver uncertainty and dyadic burden; (iv) candidate mechanisms linking PD and IU; (v) measurement and clinical assessment; and (vi) clinical implications and intervention targets. Within each domain, we prioritized PD‐specific empirical findings where available and used adjacent conceptual and chronic‐illness literature to clarify mechanisms, interpret gaps, and support clinical translation. Reflective quotations from the patient author (KP) are included as illustrative contextual material and were not treated as source data.

Results

The search identified a limited, conceptually broad, and methodologically heterogeneous body of literature addressing IU and related constructs in PD. Included sources comprised qualitative, mixed‐methods, and preliminary quantitative studies, along with conceptual papers relevant to uncertainty‐related processes in chronic neurological illness. Across studies, terminology and operationalization varied substantially; many papers did not assess IU directly but instead examined adjacent phenomena such as illness uncertainty, metacognitions about motor fluctuations, demoralization, shame, participation restriction, and caregiver strain. Even so, the literature converged on a consistent clinical picture: uncertainty surrounding symptom fluctuation, treatment response, future planning, and shifting identity was associated with greater anxiety, avoidance, emotional burden, reduced participation, and poorer quality of life for both people with Parkinson's disease (PWP) and, in parallel ways, their caregivers. The PD‐specific literature presently includes two studies that directly assessed intolerance of uncertainty, one PD‐specific conceptual framework, several illness‐uncertainty studies, and qualitative work in young‐onset PD, recently diagnosed PD, caregiver samples, and broader PD cohorts. ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰

Intolerance of Uncertainty

Individuals high in IU tend to appraise uncertain situations as threatening, catastrophize risks, and struggle to mobilize adaptive coping responses. The resulting pattern, including worry, avoidance, hypervigilance, and decisional paralysis, can intensify anxiety and interfere with daily functioning. ²¹ , ²² In medical contexts, these responses can also disrupt treatment engagement, as patients defer or resist health‐related choices and become less confident in care.

IU functions as a core contributing factor in generalized anxiety disorder ²³ and is implicated in depression, obsessive‐compulsive disorder, post‐traumatic stress disorder, and health anxiety, making it one of the most widely recognized transdiagnostic cognitive vulnerabilities. ⁴ Thus, IU is not merely a byproduct of psychological distress but an antecedent process that negatively affects emotional reactivity, cognitive biases, and coping strategies.

Cognitively, IU is linked to rigid thinking patterns, difficulty shifting between tasks or perspectives, and a reduced tolerance for ambiguity in decision‐making. ²⁴ Emotionally, it heightens threat perceptions and weakens regulatory strategies, contributing to physiological arousal and persistent worry. ²⁵ Behaviorally, IU drives avoidance responses like reassurance seeking, procrastination, or social withdrawal. These may reduce distress in the short‐term but ultimately reinforce uncertainty. ²⁶ Elevated IU has been linked to loneliness, particularly in vulnerable populations, as uncertainty can erode confidence in relationships and diminishes perceived social support, thereby intensifying psychological distress. ²⁷ , ²⁸

Avoidance served me initially or so I thought—looking back not uttering the words to others (or even myself) that “I had Parkinson's” was not avoidance, it was denial. Kuhan.

IU's relevance extends beyond psychiatric contexts to chronic medical conditions, particularly those characterized by fluctuating or unpredictable trajectories. ²⁹ For individuals living with illness, uncertainty may involve symptom variability, treatment response, and broader existential concerns related to identity, prognosis, and life planning. Higher IU in these scenarios is associated with greater emotional distress, poorer quality of life, and lower adherence to care. ⁵ This makes IU a useful framework for understanding why some individuals demonstrate resilience amidst illness uncertainty, while others experience pronounced vulnerability and maladjustment.

In a way, I find losing my identity to Parkinson's more challenging than losing my independence. Kuhan.

The importance of IU lies in its dual status as both a psychological mechanism and a clinical target. Evidence from cognitive‐behavioral interventions suggests that tolerance for uncertainty can be strengthened. ³⁰ IU is relevant across many contexts marked by unpredictability, including pandemics and fluctuating chronic pain, ³¹ , ³² but it is especially salient in PD, where uncertainty is woven into symptom experience, treatment response, and future planning.

As a result, IU provides a clinical target that can directly reduce distress, improve adaptive functioning, and enhance quality of life. For these reasons, IU has become an increasingly prominent construct in the psychological sciences and provides a useful framework for examining adjustment to unpredictable conditions, including PD, where every day presents new challenges.

Theme 1. How Uncertainty Manifests across the PD Trajectory

PD is a heterogeneous neurodegenerative disorder in which fluctuating symptoms and uncertain progression make uncertainty a central part of daily life. Although empirical studies of IU in PD are still emerging, qualitative and mixed‐methods research shows that uncertainty arising from motor fluctuations, cognitive changes, and shifting social roles can substantially affect day‐to‐day functioning. Qualitative work in young‐onset and recently diagnosed PD suggests that uncertainty is experienced through unpredictable functioning, identity disruption, grief, and difficulty imagining the future. ¹⁴ , ¹⁹ , ²⁰ These findings underscore the relevance of IU as a framework for understanding emotional distress and adaptive challenges in PD. See Figure 1.

Figure 1.

Intolerance of uncertainty in Parkinson's disease: A conceptual model.

Motor symptom variability introduces profound unpredictability into the lives of PwP. Qualitative accounts describe how sudden shifts between “on” and “off” states can erode confidence in performing even basic tasks. Cassidy and colleagues ³⁰ note that people with PD often experience “an interrupted life” marked by the strain of asynchronous motor and non‐motor symptoms, undermining autonomy, sense of self, and life trajectory. This unpredictability can lead patients to avoid social engagements, close relationships, or even routine tasks for fear of becoming incapacitated in public or having no help available. Brown and Fernie ¹⁰ similarly found that metacognitive factors, including IU were linked to anxiety and distress related to motor fluctuations. For individuals with elevated IU, symptom unpredictability, and the possibility of stigma it carries, may therefore intensify avoidance even when symptom severity alone does not fully account for it. ³¹

Anxiety in PD is often deeply rooted in uncertainty about symptom progression, medication efficacy, and social perception. Blundell et al ⁹ reported that anxiety is not merely a clinical symptom but an existential struggle permeating body, mind, and identity, with profound consequences for well‐being and quality of life. Psychological distress is exacerbated when patients ruminate over future decline or the deterioration of relationships. ³² High IU may magnify these responses, leading to cyclic worry, emotional fatigue, and reluctance to engage with healthcare providers or discuss future care options, further compounding emotional burden and depressive symptoms.

When I couldn't get the answers I needed, the only certainty I had was the uncertainty, and an unknown future was the scariest part. Over‐time and perhaps with age, I realized uncertainty was part of life, and there are always going to be things outside of my control. It's not something I embraced as such, but it re‐enforced my belief of the “living for the day.” In that sense the certainty of today provided a useful counterbalance to an uncertain future. Kuhan.

Cognitive challenges in PD, including impaired planning, working memory deficits, and slowed processing, disrupt engagement in routine tasks and decision‐making. Cognitive impairment manifests in behaviors including task omissions, trial‐and‐error actions, and reduced participation in daily activities, a phenomenon termed “cognitive ADL impairment.” ³³ Patients and caregivers frequently report frustration and anxiety related to these subtle but impactful changes; for example, forgetting steps in cooking or medication adherence. For individuals with high IU, these lapses may trigger heightened self‐doubt and fear of further decline, reinforcing withdrawal from previously meaningful activities. This link to IU is clinically plausible because IU is associated with cognitive rigidity and difficulty tolerating ambiguous or incomplete feedback. ²⁴ , ²⁵ In PD, everyday lapses may therefore be interpreted not simply as isolated mistakes but as uncertain signs of worsening function or impending decline. For individuals with high IU, that appraisal can intensify self‐doubt, anticipatory fear, and avoidance of previously meaningful activities.

Living with PD requires ongoing renegotiation of identity and life roles. Qualitative studies describe how individuals grapple with themes such as “striving for independence” and “unraveling identities,” reflecting the effort to maintain a coherent sense of self amid changing capabilities, relationships, and aspirations. ³⁰ Coupled with uncertainty about disease trajectory and future care needs, patients often oscillate between acceptance and denial, and fear and adaptation. Fekonja et al ³⁴ further highlight the dynamics of psychosocial adjustment among patients and family members, noting that uncertainty about disease progression, caregiving needs, and future dependencies contributes substantially to emotional strain for both parties. See Figure 2 and Table 1.

There's a fine line between acceptance and denial; or rather, my acceptance journey mirrors my Parkinson's journey. Every new stage, new symptom or new treatment means the cycle repeats, and it seems never ending. Kuhan.

Figure 2.

Disease progression and uncertainty.

TABLE 1.

Parkinson's disease studies addressing intolerance of uncertainty and related uncertainty constructs

References	Study type	Population / sample	Uncertainty construct	Main uncertainty‐related finding
Lawson et al 12	Pilot intervention study (Direct IU)	PwP randomized to guided self‐help versus control; N = 54 enrolled; analyzable n = 32	Intolerance of uncertainty (IU) in the context of worry	Within the guided‐reading group, worry and IU decreased significantly, but there were no significant between‐group differences at follow‐up.
Brown and Fernie 10	Cross‐sectional (Direct IU)	Adults with idiopathic PD; N = 106 (93 with off‐periods)	IU within anxiety/off‐period distress	IU was modeled alongside metacognitive variables, but metacognitive beliefs—especially uncontrollability/danger—were more strongly linked to anxiety and off‐period distress than motor severity or cognitive status.
Austin et al 13	Conceptual review/framework	Not applicable	Uncertainty in illness and psychological stress in PD	Proposed a PD‐specific framework linking unpredictable symptoms and disease progression to uncertainty, psychological stress, neuroendocrine‐immune pathways, and downstream symptom/health outcomes.
Ahn et al 14	Cross‐sectional	PwP in Korea; N = 120	Illness uncertainty	Higher illness uncertainty was significantly associated with greater depressive symptoms; uncertainty, poorer perceived health, and fatigue were significant correlates of depression.
Ravenek et al 15	Qualitative grounded theory	Young‐onset PD; 39 participants plus 14 autobiographies	Lived uncertainty in YOPD	Uncertainty was organized around identity disruption and unpredictable functioning; participants described loss of control, grief, and difficulty charting the future.
Hurt et al 16	Qualitative (caregivers)	Spousal carers of PwP; N = 18	Illness uncertainty in carers	Caregiver uncertainty extended beyond symptoms/prognosis to medical management, self‐management, social functioning, impact, and an added carer‐role domain, suggesting standard measures may undercapture caregiver uncertainty.
Choi et al 17	Cross‐sectional path analysis	PwP; N = 206	Illness uncertainty	Disease severity, social support, and resilience showed direct effects on uncertainty; economic status and disease severity also showed indirect effects through social support and resilience.
Simpson et al 18	Qualitative	PwP during UK COVID‐19 lockdown; N = 10	Illness uncertainty	COVID‐19 amplified pre‐existing PD‐related uncertainty. Participants described practical and psychological strategies to manage uncertainty, including control‐seeking, planning, and benefit‐finding.
Wang et al 19	Cross‐sectional mediation study	PwP in China; N = 268	Illness uncertainty	Post‐traumatic growth was negatively associated with illness uncertainty, and psychological capital—especially resilience and hope—fully mediated that relationship.
Aboelzahab et al 20	Qualitative	Recently diagnosed PwP (<5 years since diagnosis); N = 13	Prognostic uncertainty and psychological stress	Participants described major psychological stress related to prognostic uncertainty, including diagnostic impact, intrapersonal responses, social relationships, healthcare‐system interactions, and support‐service gaps.
Trahair et al 21	Qualitative	PwP; N = 20	Fear and uncertainty	Participants reported diverse anticipatory fears and uncertainties about future functioning and quality of life; many had not disclosed these fears to clinicians.

Theme 2. Psychosocial Consequences of IU in PD

IU intersects with cognitive and emotional processes. In the transactional stress model, ³⁵ high IU leads to heightened threat appraisals and perceived coping deficits. It is linked to cognitive inflexibility and emotion‐regulation deficits and reflects executive‐control processes, often impaired in PD, such that higher IU predicts greater stress and anxiety. ²⁵ High IU favors avoidant coping (eg, reassurance seeking, procrastination), perpetuating distress and contributing to demoralization (helplessness, hopelessness, and meaning loss) and depression in PD. ¹³ , ³² , ³⁶ Resilience buffers IU's impact on anxiety, especially in chronic conditions. ¹⁸ , ³⁷ Age‐related differences in IU have been observed across adulthood, and women with PD report distinct psychosocial burdens and unmet needs, suggesting that uncertainty may not be experienced uniformly across subgroups, although PD‐specific moderation analyses remain limited. ³⁸ , ³⁹ Recent work on PD‐related shame is conceptually complementary to IU. When unpredictable symptoms, visible changes, or loss of control threaten valued identities, uncertainty may be experienced not only as anxiety provoking but also as shame evoking, with downstream effects on self‐evaluation, social participation, and quality of life. ⁴⁰ Accordingly, IU can be conceptualized as a trait‐like risk factor (eg, relatively stable but modifiable) that shapes appraisals, coping styles, and stress responses. Its influence across psychological processes makes it a compelling lens for examining emotional adjustment in populations where uncertainty is unavoidable: those living with PD.

Theme 3. Care Partner Uncertainty and Dyadic Burden

Caregivers of PWP also face pervasive uncertainty about symptom progression, the timing of increased support needs, and the impacts of care giving on their own health, employment, and relationships. In a qualitative study of spousal carers, Hurt and colleagues ¹⁵ found that uncertainty extended beyond symptoms and prognosis to medical management, self‐management, social functioning, overall impact, and the caregiving role itself. This broader uncertainty may contribute to distress, burnout, and reduced resilience. ⁴¹ Interventions that normalize uncertainty, support boundary‐setting, and encourage flexible coping may therefore lessen caregiver burden. Practical supports, including respite care, shared caregiving roles, and structured future planning, may further reduce overload and improve well‐being.

A dyadic perspective is especially important because patient and care partner uncertainty likely interact. ⁴¹ , ⁴² Patient avoidance, distress, or reluctance to discuss future needs may heighten caregiver apprehension, while caregiver worry or overprotection may inadvertently reinforce patient avoidance. This has direct translational implications: interventions may be more effective when they address shared uncertainty, communication, future planning, and role negotiation at the dyadic or family level.

Theme 4. Potential Mechanisms Linking IU and PD

Understanding the relevance of IU in PD requires consideration of how neurological and physiological changes compromise the capacity to manage unpredictability. Three mechanisms appear central: alterations in brain circuits, dopamine dysregulation, and disruptions in the stress response system.

In PD, neural networks that support flexible thinking and adaptive behavior are disrupted. This disruption affects the ability to adjust to uncertain circumstances, leading to heightened discomfort with ambiguity and tendencies toward either overpreparation or withdrawal. ⁴³ In parallel, the degeneration of dopaminergic pathways alters reinforcement learning, impairing the balance between learning from rewards and punishments. This imbalance makes it more difficult to anticipate outcomes or trust that behaviors will reliably produce expected results. Such disruptions may intensify prospective IU by amplifying anticipatory worry and may heighten inhibitory IU by fostering decisional paralysis when outcomes appear unpredictable. ⁴⁴ , ⁴⁵

In addition, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis contributes to maladaptive responses to stress. Individuals with PD frequently report that stress exacerbates both motor and non‐motor symptoms, and empirical studies confirm altered cortisol rhythms in this population. ⁴⁶ When daily uncertainties repeatedly activate this dysregulated stress system, IU may be reinforced, linking unpredictability with heightened anxiety, fatigue, and avoidance. These mechanisms illustrate that IU in PD is not solely a cognitive or psychological trait but rather reflects the interaction of disrupted brain circuits, dopamine‐dependent learning processes, and stress physiology. This convergence may help explain why uncertainty in PD is experienced so pervasively, shaping not only responses to motor fluctuations but also broader challenges in decision‐making, long‐term planning, and emotional well‐being. ²⁰ This interpretation is consistent with Austin et al, ¹² who proposed a PD‐specific biobehavioral framework linking symptom unpredictability and disease progression to uncertainty, psychological stress, neuroendocrine‐immune pathways, and downstream symptom burden.

Theme 5. Measurement and Clinical Assessment of IU in PD

Assessment of IU in PD should not be limited to anxiety symptoms alone. In clinical settings, uncertainty more often presents across several overlapping areas: the unpredictability motor and non‐motor symptoms and variable treatment response, including wearing‐off, delayed or absent “ON” responses, dyskinesias, unpredictable “OFF” episodes, and non‐motor fluctuations, ⁴⁷ , ⁴⁸ fatigue, ⁴⁹ cognitive lapses/cognitive impairment, ⁵⁰ and autonomic changes ⁵¹ ; cognitive‐affective reactions such as anticipatory worry, ²⁰ , ⁵² hypervigilance or heightened threat monitoring, ⁵³ and difficulty making decisions ⁵⁴ ; psychosocial effects including avoidance or activities, ⁵⁵ social withdrawal, ⁵⁶ reduced participation, ⁵⁶ and trouble planning ⁵⁴ ; and self‐related consequences such as threatened identity, ⁴⁰ , ⁵² lower self‐esteem, ³¹ , ⁴⁰ shame and embarrassment, ⁵⁷ demoralization, ³² , ⁵⁸ , ⁵⁹ and poorer quality of life. Viewing IU through this broader clinical lens may help clinicians recognize forms of uncertainty‐related burden that patients often describe but are easily overlooked in routine visits.

For measurement, the Intolerance of Uncertainty Scale (IUS) ² and especially the IUS‐12 ⁶⁰ remain the most reasonable starting points, particularly because the two direct PD studies of IU used IUS‐based assessment. ¹⁰ , ¹¹ At the same time, we found no psychometric validation study of either measure in idiopathic PD. Until such work is done, assessment will likely be strongest when it draws on more than one method. In PD‐specific research, broader illness‐uncertainty measures such as the Mishel Uncertainty in Illness Scale have already been used in relation to depressive symptoms, resilience, and psychological capital, ¹³ , ¹⁶ , ¹⁸ while caregiver work suggests that standard measures may not fully capture the breadth of carer uncertainty. ¹⁵

In practice, routine history taking can be extended with brief questions about whether unpredictability has made patients feel embarrassed, less confident, less like themselves, or less willing to engage in valued activities. Pre‐visit symptom diaries, medication‐cycle logs, and caregiver input may also help clarify when uncertainty is contributing to reassurance seeking, overplanning, postponement, or withdrawal. These steps would make assessment more clinically complete and could guide more tailored intervention planning. Future work should determine whether these measures show adequate reliability, factor structure, and sensitivity to fluctuating motor and non‐motor burden in PD, and whether they can be distinguished clearly from depression and anxiety.

Theme 6. Clinical Implications and Interventional Targets

IU is a common manifestation to motor and non‐motor fluctuations, treatment response, and prognostic ambiguity in PD. Qualitative studies of recently diagnosed PD and broader PD cohorts suggest that this uncertainty is especially salient around prognosis, future functioning, and fears that may never be voiced directly to clinicians. ¹⁹ Clinicians should normalize IU as an understandable response to living with a disorder defined by unpredictability. Explicitly naming and addressing IU may validate distress, reduce stigma, and strengthen the therapeutic alliance. ⁶¹

It took me years to understand that Parkinson's was impacting my mood and motivation as well as my movement. When I realized that, I became more forgiving of myself. I'm not sure I was accepting the condition but at least I was accepting myself, and that gave me comfort. Kuhan.

From the day of diagnosis, PWP confront the reality of a progressive, incurable condition. Prodromal and at‐risk populations likewise live with the stress of an uncertain future. Stigma adds further strain, particularly in societies shaped by ageism and ableism. ³¹ Young‐onset PD, women, and racially minoritized individuals often face identity disruptions. ⁹ , ³⁸ A shame‐informed lens may therefore strengthen clinical translation: recent PD evidence suggests that shame is multifactorial, closely tied to anxiety, apathy, and poorer quality of life, and is plausibly intensified when symptom unpredictability and threatened identity converge. ⁴⁰

With progression, symptoms become more variable, and treatment response is less predictable. Motor fluctuations range from immobility in “off” states to oscillations between tremor and dyskinesias. Non‐motor changes (eg, anxiety, mood swings, fatigue, cognitive lapses) substantially impair quality of life, yet often remain invisible to others. ⁸ Additional complications include dysautonomia and medication side effects like nausea and daytime sleepiness. Together, these intersecting and fluctuating symptoms can feel overwhelming; patients liken the experience to “riding multiple rollercoasters at once.” Tracking and communicating this shifting burden are often difficult, complicating clinical care and psychosocial support. In practice, clinicians can make this burden more visible by using brief pre‐visit symptom diaries or smartphone logs, reviewing symptoms across the medication cycle, inviting caregiver corroboration when available, and ending visits with one or two concrete action steps or contingency plans for common “off” scenarios. ⁶¹ , ⁶² , ⁶³

Fluctuations (ON/OFF) added to this cycle. One minute I'm fine, the next I'm not. This constant daily up/down… it's like the condition is toying and teasing you in a cruel way. Throw in the catch 22 of dyskinesia (where the medication becomes a necessary evil), and it can really wear you down.

In PD, stigma and neuropsychiatric symptoms may initiate social withdrawal, while heightened IU may further drive avoidance of ambiguous social situations. Together, these processes may amplify loneliness, which is consistently linked with poorer well‐being and quality of life. ³¹ , ⁶⁴ , ⁶⁵

Psychological Interventions

Cognitive‐behavioral therapy (CBT) approaches that target IU, through techniques like exposure to uncertainty and cognitive restructuring, are well supported in anxiety disorders. ⁶⁶ Direct PD evidence remains preliminary but encouraging: in a pilot‐guided self‐help intervention, Lawson et al ¹¹ observed within‐group reductions in worry and IU. In PD, such approached should be adapted for cognitive slowing, motor limitations, and fatigue. Simple graded exercises like slowly adjusting to minor changes in medication timing or practicing flexible daily routines can build tolerance for ambiguity. Complementary approaches, such as Acceptance and Commitment Therapy (ACT) and Mindfulness‐Based Cognitive Therapy (MBCT), promote the acceptance of uncertainty and reduce experiential avoidance. Early trials in PD populations show that mindfulness practices, such as guided meditation or body scans, improve quality of life and reduce stress reactivity. ⁶⁷ , ⁶⁸ Teaching patients to “observe uncertainty without judgment” may mitigate cycles of worry and avoidance. Other mindfulness‐based teachings, including staying in the present moment (instead of ruminating about the past or the future), letting go of the need to control, and gratitude practices, can further mitigate worry and avoidance cycles.

Spiritual and religious coping may offer another tool for managing uncertainty. Such frameworks and rituals can provide meaning and comfort in the face of unpredictability. In PWP, spiritual well‐being is associated with reduced depressive symptoms, greater resilience, and improved quality of life. ⁶⁹ , ⁷⁰ Integrating practices like prayer or existential reflection into therapy can strengthen patients’ capacity to navigate uncertainty.

IU often evokes fears about identity loss, diminished roles, and the future. Interventions that foster meaning in life (MiL), such as dignity therapy, logotherapy‐inspired counseling, and narrative medicine, may help patients reframe uncertainty in ways that preserve values and purpose. ⁷¹ , ⁷² These may be particularly impactful in PD, where patients continually renegotiate identity and autonomy. Compassion‐focused therapy and resilience‐based frameworks can further strengthen psychological capital (hope, optimism, self‐efficacy, and resilience), lessening IU's impact on quality of life. ⁷³ This emphasis on hope and resilience is also consistent with PD data showing that psychological capital may mediate the relationship between post‐traumatic growth and illness uncertainty. ¹⁸ These approaches can be integrated into individual or group‐based programs tailored for PWP, promoting adaptive coping amid chronic uncertainty.

Psychosocial Options

A core principle for managing IU in PWP is distinguishing between controllable and uncontrollable aspects of life. Predictability can be strengthened through consistent routines, medication timers, wearable devices, and regular exercise and sleep schedules. ⁷ Flexible contingency plans, such as preparing for medication “off” periods, may also reduce anticipatory anxiety. Qualitative evidence suggests that people with PD already use control‐seeking, planning, and benefit‐finding to manage uncertainty, indicating that structured versions of these strategies may be clinically acceptable targets. ¹⁷

Structured problem‐solving and goal‐setting skills manage perceived chaos. Incremental adaptations like pacing tasks or planning for motor fluctuations may help build tolerance for change and enhance agency. Stress exacerbates IU and PD symptoms; therefore, relaxation training, paced breathing, progressive muscle relaxation, and biofeedback may disrupt the IU–stress cycle. ⁷⁴ Technology‐based delivery, such as smartphone‐guided relaxation or telehealth programs, expands accessibility.

Social isolation often worsens IU, making peer support vital. Group settings allow PWP to share strategies for navigating unpredictability, normalizing IU and reducing shame. Observing peers adapt successfully strengthens coping and hope. Peer mentoring, particularly when mentors share characteristics like age, race, gender, or disease stage, enhances trust and relatability. ⁷⁵ Culturally sensitive adaptations, aligned with patients' values and communication styles, are critical for engagement, especially in diverse PD populations.

Educating and empowering patients and their caregivers is foundational to comprehensive care. For many, simply having their emotional responses to uncertainty normalized can lessen distress and prevent the sense of being “alone” in their experience. ⁶² Providing clear education and consistent support creates a foundation on which adaptive coping can be built. Importantly, proactive strategies, like meeting with members of the multidisciplinary care team before difficulties escalate into crises or safety concerns, offer patients and families a greater sense of preparedness. Similarly, structured approaches like annual screenings or check‐ins can serve as a practical “road map,” anticipating challenges before they emerge and thereby reducing the burden of uncertainty. ⁶³ , ⁷⁶

Medical interventions may indirectly reduce IU by alleviating psychiatric and motor symptoms. Pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs), serotonin‐norepinephrine reuptake inhibitors (SNRIs), and dopaminergic agents may decrease anxiety and depressive symptoms, lessening the clinical impact of IU. ⁷⁷ Careful monitoring remains essential, as dopaminergic fluctuations can heighten unpredictability. Complementary approaches including yoga and tai chi can enhance bodily awareness, stress regulation, and self‐efficacy, indirectly easing IU. ⁷⁸

These strategies aim not to eliminate uncertainty, which is impossible in PD, but to preserve confidence, agency, and quality of life in the face of a progressive illness.

Conclusion

IU represents a critical but underexamined construct in PD. As this review highlights, IU permeates the lived experience of PD by intensifying anxiety, avoidance, and maladaptive coping across motor, cognitive, psychiatric, and social domains. Its relevance stems not only from the disorder's inherent unpredictability, manifest in motor and non‐motor fluctuations, medication variability, and ambiguous prognoses, but also from potential neurobiological mechanisms linked to dopamine dysfunction, executive impairment, and stress system dysregulation. Together, these factors create a perfect storm in which IU can undermine adaptation, erode quality of life, and exacerbate caregiver burden.

Viewing IU as a common risk factor in PD points to new ways to support patients, improve function, and reduce distress. Adapted cognitive‐behavioral and metacognitive approaches that directly target uncertainty, alongside meaning‐centered and resilience‐based approaches, may mitigate its impact and promote more adaptive adjustment. Embedding IU screening and management into multidisciplinary care pathways could normalize its presence, validate patient and caregiver distress, and guide the tailoring of psychosocial supports. At the same time, further empirical research is needed to establish prevalence rates, delineate IU's unique manifestations in PD, and evaluate targeted treatment strategies.

Addressing IU may strengthen both clinical assessment and supportive care in PD. By explicitly naming and targeting this construct, clinical care can move beyond symptom management to directly address the psychological mechanisms that amplify suffering. Such an approach may help sustain resilience, identity, and quality of life for patients and caregivers navigating the pervasive uncertainties of PD.

Sometimes I think a condition that is more crippling but more black & white, more constant perhaps, would that be more bearable than the shades of grey that is Parkinson's? Kuhan.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of first draft, B. Review and Critique.

B.M.: 1A, 1B, 1C, 3A, 3B

G.P.: 1A, 1B, 1C, 3B.

K.P.: 3B.

I.S.: 1A, 1B, 1C, 3B

Disclosures

Ethical Compliance Statement: Neither Institutional Review Board approval nor informed patient consent were necessary for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: There was no funding for this project. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Financial Disclosures for the Previous 12 Months: G.M.P. reports consulting or advisory relationships with Acadia Pharmaceuticals Inc. and with GE Healthcare. I.S. received a speaker honorarium from Acorda. B.M. and K.P. have no financial disclosures.

Financial Disclosures and Conflicts of Interest

Author disclosures are available in the Supporting Information.

Supporting information

Data S1. Coi_disclosures.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.