Childhood Trauma and Parkinson Disease

Abstract

Background and Objectives

Childhood trauma has been shown to be associated with adverse health outcomes that can last a lifetime. The effects of trauma have not been evaluated in a Parkinson disease (PD) population. The goal of this study was to survey individuals with PD to evaluate whether the intensity of childhood trauma is associated with individual symptoms, overall disease severity, or quality of life.

Methods

An Internet-based observational survey was designed to evaluate modifiable variables associated with PD progression. In this cross-sectional analysis, adverse childhood experiences (ACEs) were used as a measure of childhood trauma, patient-reported outcomes in PD for the primary measure of PD severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) Global for quality of life (QoL).

Results

Seven hundred twelve of 900 participants (79%) responded to the questions related to childhood trauma. Among respondents, QoL decreased as incidence of childhood trauma increased. Individuals with ACE scores 4 or higher reported greater symptom severity for 45% of the variables tested, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (p < 0.05) compared with individuals with trauma scores of zero.

Discussion

These data suggest childhood trauma is associated with a mild increase in overall patient-reported PD severity, specifically mood and other nonmotor and motor symptoms. While the associations were statistically significant, the impact of trauma was less robust than previously described predictors of severity, such as diet, exercise, and social connection. Future research should attempt to include more diverse populations, attempt to improve the response rate of these sensitive questions, and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.

Adverse childhood experiences (ACEs) are described as potentially traumatic events that can have cumulative and long-term negative effects on health and development and include exposure to abuse, neglect, and household dysfunction.¹ ACEs are common in all countries around the world and affect 1 billion children of ages 2–17 years globally.² The association between ACEs and subsequent medical conditions in adulthood has been a focus of much research since the seminal investigation by Kaiser Permanente and the Centers for Disease Control and Prevention,³ which revealed a significant positive association between the number of exposures to childhood adversity and a variety of adult health risks. Specifically, those with 4 or more exposures had significantly greater odds of alcoholism, depression, suicide attempts, drug abuse, smoking, physical inactivity, and severe obesity. Since the publication of these findings, a robust body of literature has clearly established a connection between ACEs and negative physical and psychosocial health outcomes across the lifespan including stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature mortality.^4-8 Results from biomedical studies indicate that ACEs directly affect neurologic, hormonal, and immunologic development.⁹ In addition, the findings by Kaiser have been supported more recently by increased reports of the correlation between ACEs and mental health consequences such as anxiety, depression,¹⁰ substance use, and suicide.⁵ Currently, Parkinson disease (PD) is not listed among other health care diagnoses including dementia, migraine, and stroke that are associated with ACEs in the current algorithm.¹¹ Hence, the cutoff for referral for resources is at an ACE score of 4 or more. As more data accumulate in PD and trauma, we may be able to advocate for adding PD as a diagnosis associated with ACEs and, therefore, push to allocate more resources for those affected at the lower threshold of an ACE score of 1 or more or possibly a different cutoff.

The exact cascade of changes after ACEs that lead to poor health outcomes in adults remains elusive, but some literature posits explanations. A child exposed to adverse events and toxic stress is at risk of developing permanent changes to brain architecture, epigenetic alteration, and altered gene function.^12,13 The body's response to elevated stress associated with ACEs includes dysregulation of the hypothalamic-pituitary-adrenal axis and prolonged cortisol activation and a persistent inflammatory state,¹⁴ which are believed to play a role in the evolution of a variety of adult health conditions.^15,16 Accumulating evidence supports the hypothesis that ACEs results in morphological changes to several brain structures including the hippocampus, amygdala, prefrontal cortex, cerebellum, and corpus callosum,¹⁷ which may lead to increased vulnerability to pathology partly due to changes in emotional and cognitive systems.¹⁸ Last, adult mental health conditions are partly heritable, and through specific gene/environment interactions, a range of genetic variations (polymorphisms) can increase the risk of diseases in adulthood.¹⁹

The prevalence of ACEs in the general population is staggering: 1 in 6 adults experience 4 or more types of ACEs.²⁰ Individuals with neurologic disorders have been reported to have higher ACEs compared with the US population estimate and were more likely to have comorbidities, including depression and anxiety,²¹ which are also common in up to 50% of people with PD (PwP)²² and contribute to motor manifestations of tremor and dyskinesia.²³ Higher ACE scores have been associated with worse symptoms of functional neurologic disease,²⁴ earlier onset of multiple sclerosis,^25-27 and dementia in older Japanese adults.²⁸ Despite the growing body of evidence that high ACEs have adverse neurologic and psychological consequences, the relationship between ACEs in PD is yet to be investigated. The purpose of this study was to expand the field by investigating the relationship between ACEs and PD symptoms, disease severity, and quality of life (QoL) and to lay the foundation for possibly reclassifying PD as an ACE-related condition to provide additional support to PwP with ACEs above 1 or possibly a different cutoff.

Methods

The Modifiable Variables in Parkinsonism (MVP) study is a prospective Internet-based natural history study (N > 2,700) of a cohort of individuals with parkinsonism designed to identify modifiable variables associated with PD progression and symptom severity. The Bastyr University institutional review board has provided oversight (IRB #11A-1301; Clinical Trials #NCT02194816) and a Waiver of Documentation of Informed Consent for this project. All individuals acknowledged that they both read and understood the participant information sheet before answering study questions. Individuals are asked to fill out surveys, approximately 60–90 minutes twice a year, and while each survey has a consistent set of questions, additional questions intended to inquire about specific topics are added and removed with each iteration. Participants do not need to complete the survey in 1 sitting. Only survey responses between February and August 2021, which contained data specific to adverse childhood events, were included for this cross-sectional analysis. Only individuals reporting a diagnosis of idiopathic PD were included; those with other forms of parkinsonism were excluded. For individuals who completed the survey twice within the selected time frame, the most recent survey response was kept, and any prior submissions were removed. Study data were collected and managed using Research Electronic Data Capture (REDCap) hosted at the Bastyr University. REDCap is a secure Internet-based platform designed for secure research data capture, providing the following: (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources.²⁹ Checklist for Reporting Of Survey Studies³⁰ reporting guidelines were adhered to for manuscript preparation and output.

To obtain data on childhood trauma, a validated ACE scale was added to the ongoing longitudinal MVP study. The MVP study used the patient-reported outcomes in PD (PRO-PD) to assess parkinsonian symptom severity. The PRO-PD is calculated as a cumulative score of 33 common PD symptoms, each out of 100, with a maximum total score of 3,300. No weighting of items or propensity scores were used. Each symptom is presented to the respondent, asking them to describe the severity of the symptom using a slider bar. The bars are labeled 0 (healthy) to 100 (debilitating) as the user is asked to slide a tab (numerical value not visible) to the left or right as an indication of that symptom's average severity over the course of the previous week. PRO-PD scores have been shown to increase over time and correlate with Unified Parkinson's Disease Rating Scale H + Y, Parkinson's Disease Questionnaire-39, Timed Up and Go, and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global QoL survey.³¹ For this analysis, the total PRO-PD score and individual symptom scores were used as outcome measures.

Childhood trauma was measured by the validated scale of total ACEs (ACE score),³ and QoL was measured using PROMIS Global.³² The ACE questionnaire was added in 2021 and because it does not change, the questions are asked only once during the longitudinal observational study. On enrolling in the study, participants are alerted to the risk of stress or discomfort as a consequence of study participation. Participants are encouraged to contact their local primary care provider, neurologist, and crisis center, and the study enrollment materials provide a toll-free crisis hotline number for individuals in the United States and email and phone number for the MVP study staff are available on the study website.

ACE score was calculated as the sum of the score for each of the 10 questions in the ACE questionnaire (yes = 1 and no = 0). The layout of the radar chart of patient-reported symptoms was organized by the authors with nonmotor symptoms on the right side of the chart and motor symptoms on the left to loosely create domains of clinical and physiologic similarity. Multiple linear regression models were used to examine the association between ACE score and overall PD severity, with PRO-PD scores used as the outcome variable. Both the total PRO-PD and motor subset of the PRO-PD (impaired handwriting, slowness, tremor, stooped posture, difficulty walking, difficulty speaking, difficulty rising from a seated position, difficulty dressing/grooming/eating, restless legs, falling, balance, and freezing) were used as outcome measures for PD symptom severity. Along with accounting for the total ACE score, regression analyses controlled for age, years since diagnosis, income, and sex because these variables can also affect QoL and severity of disease. We aimed to remove as many potential confounders as possible. For regression analyses, participant records were excluded if age, years since diagnosis, income, and/or sex data were missing. As in prior publications using the PRO-PD, if participants failed to score one of the 33 individual PRO-PD symptoms, the cohort average for that symptom was replaced for any missing values. For QoL analysis using PROMIS, only complete data were included and no substitutions were made. While we used the continuous ACE score in understanding the point-by-point impact on trauma on symptom severity and QoL, we used categorical values to compare mean symptom severity (PRO-PD) between cohorts of total ACE scores (e.g., 0, 1–3, and 4+). These categories were chosen to match the ACE aware algorithm¹¹ and are standard for this type of stratification. To assess for statistical significance across these cohort mean values, 2-sample t tests with equal variance were performed. The latter statistical analysis used a comparison of mean values, without controlling for age, sex, income, and years since diagnosis. Therefore, we did not drop the records missing these demographic data, though they were excluded from regression analyses. We have described details of data comprehensiveness in Table 1. All statistical analyses were performed using STATA software, version 14 (College Station, TX) with alpha set to 0.05. To avoid increasing the risk of type II errors or false negatives, no adjustments were made for multiple comparisons because this study was designed to screen for possible associations.

Table 1.

Demographics

Standard Protocol Approvals, Registrations, and Patient Consents

Institutional approval was obtained from the ethical standards committee at the Bastyr University for any experiments using human subjects. Written consent was obtained for all patients participating in this study.

This MVP study was initiated with the support of the National Center for Complementary and Integrative Health under a joint NIH/Bernard Osher K01 Career Transition Award (NIH K01 AT004404). There were no photographs, videos, or other personally identifiable information collected from this study that will be used in the publication of results; therefore, no consent to disclose was necessary.

Data Availability

The authors have full access to the data used in the analysis and manuscript and take full responsibility for the conduct of the research. The authors have the right to publish all data, separate and apart from the guidance of any sponsor. Individual deidentified participant data, study protocol, and statistical plan will be available on request by any qualified researcher for 1 year after manuscript preparation. Investigators can access the data request form at: redcap.bastyr.edu/redcap/surveys/?s=MTND8FM4XY.

Results

Of the 959 individuals with parkinsonism who responded to the questionnaire containing the variables of interest, 900 reported a diagnosis of idiopathic PD. Of them, 188 individuals (21%) chose not to answer the questions related to childhood trauma, resulting in a study of 712 individuals. Contrary to PD population demographics, most participants in this study were women.³³ While all income and education brackets were represented, most participants reported annual incomes greater than $80,000/y Approximately 76% of participants were living in the United States, and 91% of participants were identified as White, which is not representative of populations living with PD in general (Table 1).³⁴

PRO-PD scores, adjusted for age, sex, income, and years since diagnosis, increased as ACE score increased. The regression model coefficient suggested a predicted 35-point increase (roughly 1% worsening) in PRO-PD score for each additional point on the ACE questionnaire (p = 0.001; 95% CI: 15.16–54.19) (Figure 1). Using the PROMIS rating scale, higher scores for childhood trauma were associated with lower QoL, with each ACE point being associated with a coefficient predicted 0.5-point decrease (worsening) in PROMIS score (p = 0.001; CI: −0.78 to −0.21). Although there was a statistically meaningful difference in QOL outcomes between participants with 0 ACE and those with 1–3 ACEs (p = 0.0002) and those with 4+ ACEs (p = 0.0009), the difference between those with 1–3 ACEs and those with 4+ ACEs was not statistically significant (p = 0.3620) (Figure 2A). Similarly, there is a statistically significant difference in PD symptom severity between participants with 0 ACE and those with 1–3 ACEs (p = 0.0013) and those with 4+ ACEs (p = 0.0042); the difference between those with 1–3 ACEs and 4+ ACEs was also not statistically significant (p = 0.4842) (Figure 2B).

Figure 1. Relationship Between PD Severity and Adverse Experiences of Childhood.

Disease severity was measured using the Patient-Reported Outcomes in PD (PRO-PD), and childhood trauma was measured using the ACE 10-point scale. Error bars are 95% CIs, and due to small sample sizes, a t distribution was assumed. ACEs = adverse childhood experiences; PD = Parkinson disease.

Figure 2. Quality of Life, Symptom Severity, and Childhood Trauma in People With PD.

(A) Quality of Life and Childhood Trauma in People with Parkinson disease. Error bars indicate 95% CIs assuming a normal distribution. A t test comparing the mean PROMIS total of individuals reporting ACE scores of 0 vs ACE scores of 4 or higher yielded a p value of 0.0009; while comparing ACE scores of 0 vs ACE scores between 1 and 3 yielded a p value of 0.0002; however, a t test comparing those with ACE scores between 1 and 3 and those with ACE scores 4 or higher yielded a statistically insignificant p value of 0.3623. (B) Symptom Severity and Childhood Trauma in People with PD. Error bars indicate 95% CIs assuming normal distribution. A t test comparing the mean PRO-PD scores of individuals reporting ACE scores of 0 vs ACE scores of 4 or higher yielded a p value of 0.0042; while comparing ACE scores of 0 vs ACE scores between 1 and 3 yielded a p value of 0.0013; however, a t test comparing those with ACE scores between 1 and 3 and those with ACE scores 4 or higher yielded a statistically insignificant p value of 0.4842. ACEs = adverse childhood experiences; PD = Parkinson disease; PRO-PD = patient-reported outcomes in PD.

The following variables were also associated with greater symptom severity: male sex, lower income brackets, older age, and more years with PD. The symptoms that were most strongly correlated with childhood trauma were apathy, myalgia, fatigue, daytime sleepiness, restless leg syndrome, depression, anxiety, cognitive complaints, and a variety of other nonmotor symptoms (Table 2).

Table 2.

Symptoms Associated With Multiple Childhood Traumas

An analysis of the PRO-PD motor subset found a statistically significant effect of ACEs on motor symptoms when controlling for age, sex, income, and years since diagnosis. The coefficient suggests an 11-point worsening of motor symptoms for every 1-point increase in ACE score (p = 0.007; 95% CI: 2.958–18.196).

The symptoms most strongly associated with trauma were predominantly nonmotor including apathy, depression, anxiety, myalgia, daytime sleepiness, fatigue, restless leg syndrome, comprehension, forgetfulness, and constipation. Nausea and dyskinesia, symptoms predominantly understood to be medication side effects, were also higher in individuals with more childhood trauma (Figure 3).

Figure 3. Individual Parkinson Symptoms Associated With Childhood Trauma.

Symptom severity was measured on slider bars with the left anchor (score = 0) denoting wellness and an anchor on the right (score = 100) denoting debilitating symptom severity. Asterisks represent a statistically significant difference in symptom severity between those reporting ACE scores of 0 and those reporting ACE scores of 4 or higher.

Discussion

The role of ACES and trauma has thus far not been explored in PD. This study may demonstrate a dose-dependent relationship between childhood trauma, PD symptoms, and QoL in PwP. As anticipated, individuals with the least reported childhood trauma reported the highest current QoL and lowest patient-reported symptom burden, both motor and nonmotor, compared with those with higher reported childhood trauma. Specifically, patients who reported greater than 1 ACE all experienced a statistically significant decrease in QoL, and for each additional ACE, there was significant worsening of motor symptoms. The results relating to the worsening of motor symptoms with increases in ACEs are of particular interest to PwP because progression of motor symptoms is one factor associated with subjective QoL. The effect of ACEs on motor symptoms in PD is one area that sets these data apart from other neurologic conditions.

The results are compelling despite the significant proportion of participants (21%) who did not respond to the questions about ACEs, which may have skewed the results. It is possible that individuals with fewer ACEs may be more likely to enroll in research studies because of their better health and engaged lifestyles, and research affirms that adults who have been exposed to ACEs frequently neglect to disclose because of shame and fear of stigmatization.³⁵ High ACE scores have been shown to increase the risk of adverse health outcomes, poverty, and addiction, which may also influence the overall ability to participate in research. This is a 90-minute survey, and it is possible that survey fatigue contributed to missing data, but it is also possible that the sensitive nature of these questions led to participants intentionally choosing not to answer them. In the survey, the section following ACEs relates to the individuals' use of medications; of the 900 participants, 85% answered the medications section, while only 79% answered questions about childhood trauma, suggesting survey fatigue is unlikely the explanation for much of the missing data but, rather, that 6% of participants chose to selectively skip the trauma section and go on to the following section. Future studies should focus on broader outreach and exploration of ways to survey about ACEs to yield a higher percentage of participants.

While there were associations with the motor subset and a few motor symptoms (e.g., dressing, eating, and grooming) the most robust correlations were between ACEs and nonmotor symptoms of PD. The nonmotor symptoms with the most significant associations with ACE scores were as follows: loss of interest, daytime sleepiness, restless leg syndrome, lack of motivation, depression, and fatigue. Mood, motor symptoms, and nonmotor symptoms are very enmeshed in PD, making controlling for specific symptoms such as depression and anxiety complex. Because mood symptoms such as anxiety have direct effects on symptoms such as tremor or dyskinesias in these populations, it becomes hard to separate these symptoms in a clean fashion. Moreover, because anxiety and depression are also contained in the PRO-PD outcomes measure, controlling for them in this fashion is not ideal but may provide a better glimpse of the reasons for the relationship between ACEs and PRO-PD scores. “Despite attempts to control for other variables that may influence PD symptoms and QoL, it is possible that the impacts of variables not accounted for, other than ACEs, may be responsible for these results.”

There seems to be a greater degree of long-term suffering associated with childhood trauma, which clearly necessitates more focused primary prevention efforts to reduce childhood trauma from occurring in the first place but does little to help those who have already experienced trauma. The utilization of harm reduction efforts as a therapeutic strategy in adults with ACEs to reduce the impact of their childhood trauma on their current PD symptoms and QoL seems promising. Screening for ACEs on diagnosis of PD and focused use of resources in patients with PD from diagnosis including help with social support and referral to a psychologist may be helpful. Because PD is a slowly progressive neurodegenerative disease with a long course, early screening for ACEs and appropriate referrals may modify the course of the disease, especially in the nonmotor and mental health arenas. Change in public policy and resource allocation may be possible if we can increase the awareness of the impact of childhood trauma on PD and with the inclusion of PD as an ACE-associated diagnosis similar to stroke, migraine, and dementia. In addition, because PwP are at a significantly higher risk of dementia,³⁶ and memory loss/dementia is listed as an ACE-related diagnosis, inclusion of PD as an associated diagnosis should be all the more strongly considered.

Considering the significant health consequences of ACEs in adulthood, identifying evidence-based treatments is essential. Most of the available literature does not specifically focus on ACEs but rather the associated trauma, which means that interventions shown to alleviate trauma-related symptoms should be explored. Among the interventions with the strongest clinical evidence for trauma-related symptoms in adults are cognitive behavioral therapy, cognitive processing therapy, and prolonged exposure therapy. Evidence is reasonably strong for eye movement desensitization and reprocessing and narrative exposure therapy.³⁷ A growing body of literature supports the use of acceptance and commitment therapy (ACT) treatment for people with trauma,^38,39 and mindfulness, a core feature of ACT, has been shown to decrease symptoms associated with trauma in both adults and adolescents.^40,41 Integrative and mind body approaches such as yoga and meditation and increasing social support are receiving increased attention as effective interventions for a variety of mental health issues, and the evidence is growing for their efficacy in treating trauma-related symptoms.^42-44 There has been little study, in general, of these types of treatments in PD, and many may have a role even in general PD management from a lifestyle/wellness perspective. Targeted referrals after early screening for ACEs from PD diagnosis in the realm of social support and mental health support (e.g., referral to social worker, psychologist, support group) may be the way of the future. As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization. They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.

This study adds to the recently published article on trauma-informed neurology⁴⁵ and sets the stage for increased attention to this underrecognized yet needed area of holistic patient care. The findings from this study need to be considered in the context of the breadth of factors that can affect QoL outcomes of PwP. Although these data provide preliminary evidence regarding the relationship between ACE score, a variety of both motor and nonmotor symptoms, and QoL, the associations were modest and clearly warrant further investigation. Although this is the first study demonstrating a statistically significant, inverse relationship between ACEs and QoL and positive relationship between ACEs and PD symptom severity, specifically nonmotor symptoms, the practical implications remain to be seen. While the association between childhood trauma and PD severity, specifically the motor subset, is statistically significant, the relative impact of the association seems mild. For instance, using the same scale and making the same adjustments, individuals with ACEs 4+ have an estimated PRO-PD score 11 points higher than those with ACE 0, people who report having many friends have a 169-point reduction and people who exercise 30 minutes per day, 6 days per week have a 292-point reduction in score.⁴⁶ This suggests that childhood trauma has a measurable, but mild, impact on overall patient-reported symptoms. Evidence is mounting that the stress response is potentially modifiable, although much research remains on the effectiveness of various strategies for minimizing the adverse effects of stress. We remain hopeful that early proactive identification of PwP with a history of trauma may be helped by targeted interventions that may improve their outcomes and QoL.

This study has several limitations that should be considered when interpretating the data. First, the demographics of these data are skewed. The lack of racial and ethnic minority representation precludes generalizing the results to more diverse populations. While prior studies have demonstrated that men are disproportionately affected with PD, 65% of survey respondents in this study were women. Of note, 14.6% percent of women reported an ACE score >4, whereas only 7% of men reported ACEs >4; while the sex balance of this study is disproportionately female, the inclusion of women reporting more childhood trauma may have contributed to our ability to identify these associations. The level of financial security and education was also quite skewed in this study, with almost 50% of individuals in this cohort reporting a professional or graduate degree, further calling the generalizability of these data into question. Still, given the robust body of evidence suggesting childhood trauma reduces health and opportunities later in life, this higher-income, higher-education cohort is predicted to have less trauma than those in lower socioeconomic cohorts. Further research should attempt to recruit those individuals who are underrepresented in this study because they may be more severely affected.

Second, this was a cross-sectional study, which prevents making any causal determinations. Third, the study relied on self-reported PD status leading to questions of validity, although the literature indicates the accuracy of patient-reported PD diagnosis correlates highly with clinician diagnosis.⁴⁷ Fourth, the high nonresponder rate of 21% is also a limitation to this study. Fifth, the study relied on a self-administered computer-based survey that was lengthy and took a long time to complete, which may have contributed to the 21% nonresponder rate. Sixth, years since diagnosis does not accurately capture disease duration because it can be affected by access-to-care issues and those with high ACE scores might experience decreased access to care and hence a delay in diagnosis. Seventh, we did not control for additional socioeconomic factors including primary insurance payer and race. Last, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk of recall bias.

Future studies should attempt to identify the mediators or moderators of the relationship by which ACEs could lead to higher ratings on the PRO-PD scale beyond anxiety and depression. Factors such as insurance coverage, health care access, psychiatric disease, and many other variables could be mediating the relationship between ACEs and PD symptoms. Subsequent studies should attempt to include more diverse populations (e.g., race, education, and financial security), attempt to improve the response rate of these sensitive questions, use models that control for anxiety and depression, and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be proactively mitigated by screening at diagnosis and introducing lifestyle modification, social support, or other interventions. Reclassification of PD as an ACE-related diagnosis and revisiting the ACE score cutoff for more resources would have important clinical ramifications to improve trauma-informed neurologic care and should be a priority for future research goals. Changing the cutoff and allocating more resources would have significant implications for health care delivery. The overall impact of ACEs on overall PRO-PD and QoL was modest and the decision to reclassify PD as an ACE-related disorder and provide education and treatment would increase overall health care costs. These data are the first to suggest an association between childhood trauma and PD; should future studies replicate this finding, the costs of investing in prevention and treatment may be a worthwhile investment over time.

TAKE-HOME POINTS

• → This is the first study to evaluate the relationship between adverse childhood experiences and PD.

• → Adverse childhood experiences are associated with increased symptoms, both motor and nonmotor, among people with PD.

• → Adverse childhood experiences are associated with decreased quality of life among people with PD.

• → Despite the statistical significance of the results, inferring practical clinical implications will require additional research, which could pave the way for mental health and social support referral of patients with PD.

Appendix. Authors

Study Funding

This MVP study was initiated with the support of the National Center for Complementary and Integrative Health under a joint NIH/Bernard Osher K01 Career Transition Award (NIH K01 AT004404). The ongoing data collection has been supported by a donation from Sondra and Bill Fondren, neither of whom were involved in the data analysis or manuscript writing, editing, or decision to publish.

Disclosure

All authors' contributions were performed as part of their employment at their respective institutions. L.K. Mischley owns the copyright of the PRO-PD scale, which is freely available at PROPD.org. None of the other authors have any potential conflicts of interest to disclose. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.