Stroke And The Risk Of Parkinson’s Disease
Overview
This study investigates the incidence of Parkinson’s disease (PD) among stroke patients and its association with post-stroke disabilities. Utilizing data from the Korean National Health Insurance Service spanning 2010 to 2018, the study analyzed 307,361 stroke patients and 380,917 age- and sex-matched individuals without stroke. The aim was to determine whether stroke patients have an elevated risk of developing PD compared to those without stroke, and whether this risk varies according to the presence and severity of post-stroke disabilities.
Over a follow-up period of 4.31 years, stroke patients exhibited a 1.67 times higher risk of PD compared to individuals without stroke, highlighting a significant association between stroke and subsequent PD development. Furthermore, the study found that stroke patients with disabilities were at even greater risk of developing PD compared to those without disabilities. This association persisted even after adjusting for various covariates, with adjusted hazard ratios of 1.72 and 1.66 for stroke patients with disabilities and without disabilities, respectively.
The findings underscore the importance of healthcare professionals remaining vigilant in detecting movement disorders among stroke patients, as these may serve as early indicators for diagnosing PD. This study contributes valuable insights into the link between stroke, post-stroke disabilities, and the subsequent risk of PD, emphasizing the need for comprehensive care and surveillance in stroke management to address potential neurological complications.
Introduction
Stroke stands as a formidable health challenge globally, trailing only behind heart disease as the leading cause of death. Beyond its significant mortality rates, stroke imposes a heavy burden of long-term disability, further exacerbating its impact on public health. Compounding this burden is the parallel rise of Parkinson’s disease (PD), another prevalent condition, particularly among the aging population. When stroke and PD coincide, the consequences can be particularly dire, leading to compounded health complications and poorer outcomes for affected individuals.
Research has shed light on the intricate relationship between stroke and PD, revealing a complex interplay between these two conditions. Studies have consistently shown that individuals with PD who have a history of stroke face an elevated risk of hospitalization compared to those without such a history. Even the presence of silent vascular burdens, often unnoticed, can significantly influence both the motor and nonmotor symptoms experienced by PD patients. This underscores the critical need to unravel and understand the intricate connections between these two neurological disorders.
Previous investigations, spanning diverse geographic regions such as the United Kingdom, China, and Korea, have provided compelling evidence of the association between PD and stroke. Case-control studies and retrospective cohort analyses have consistently demonstrated a higher prevalence or risk of stroke among PD patients when compared to carefully matched control groups. These findings underscore the shared underlying mechanisms and risk factors that contribute to the development of both conditions, including advanced age, increased oxidative stress, and common comorbidities like hypertension, diabetes mellitus, and dyslipidemia.
Despite the wealth of research exploring the heightened stroke risk among PD patients, there remains a notable gap in understanding the reciprocal relationship—namely, the risk of developing PD among stroke patients. Moreover, the presence of involuntary movement disorders, such as parkinsonism, in poststroke individuals can pose challenges during the diagnostic process for PD, potentially leading to underdiagnosis or misdiagnosis.
To address these knowledge gaps and elucidate the risk of PD development following a stroke, a retrospective cohort study leveraging a comprehensive population-based database was devised. By systematically examining the incidence of PD among stroke patients, this study aims to provide invaluable insights into the complex interaction between these two neurological conditions. Ultimately, such insights hold the potential to inform clinical decision-making, guide early intervention strategies, and improve outcomes for individuals affected by stroke and PD alike.
Method
This retrospective cohort study utilized data from the Korean National Health Insurance Service (KNHIS) database, which covers approximately 97% of the Korean population, gathering comprehensive medical information including diagnoses, prescriptions, and health screenings. The study focused on 800,646 patients diagnosed with stroke between January 1, 2010, and December 31, 2018, identified based on International Classification of Disease, 10th revision (ICD-10) codes and brain imaging claims. These stroke patients were matched 1:1 with control subjects without stroke based on age and sex, who participated in the national health checkup program within 2 years from the index year.
After applying inclusion and exclusion criteria, a total of 307,361 stroke patients and 380,917 controls were included for analysis. The severity of disability post-stroke was assessed according to disability grades defined by the Korea National Disability Registration System (KNDRS), with disability categorized as severe or mild based on predetermined criteria. The primary outcome of the study was newly diagnosed Parkinson’s disease (PD), identified by specific ICD-10 codes and registration codes from the Rare Intractable Disease management program.
Study subjects were followed from the date of stroke diagnosis or matched index date for controls until the date of newly diagnosed PD or the end of the follow-up period (December 31, 2019). Covariates including household income, place of residence, smoking status, alcohol consumption, exercise frequency, body mass index, fasting glucose, total cholesterol levels, and comorbidities such as diabetes mellitus, hypertension, and dyslipidemia were analyzed.
Low household income, place of residence, smoking status, heavy alcohol consumption, lack of regular exercise, high body mass index, and comorbidities were among the covariates examined. The Charlson Comorbidity Index (CCI) was used to assess the overall comorbidity burden. The study was approved by the Institutional Review Board, with the requirement for informed consent waived due to the retrospective nature of the deidentified data.
In summary, this study provides valuable insights into the association between stroke and the risk of newly diagnosed PD in the Korean population, incorporating detailed demographic, clinical, and lifestyle factors from a large-scale national database.
Statistical Analysis
The study employed descriptive statistics, presenting mean ± SD for continuous variables and n (%) for categorical variables. To investigate the incidence probabilities of Parkinson’s disease (PD) in stroke patients compared to those without stroke, Kaplan–Meier analysis was utilized. Hazard ratios (HR) and their 95% confidence intervals (CI) for PD were calculated using Cox proportional hazards regression, adjusting for various factors in the multivariate model (Model 3). These factors included age, sex, socioeconomic variables (such as household income and place of residence), health behaviors (smoking status, alcohol consumption, and regular exercise), comorbidities (type 2 diabetes, hypertension, and dyslipidemia), and the Charlson Comorbidity Index (CCI) score.
Furthermore, the study examined the risk of PD based on the presence and severity of disability. A 1-year lag sensitivity analysis was conducted to assess potential surveillance bias. Statistical analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC, USA), with significance set at p < 0.05. This comprehensive analytical approach aimed to elucidate the association between stroke and PD while accounting for various confounding factors, providing valuable insights into the relationship between these two conditions.
Result
The study delved into an extensive examination of stroke patients and their matched counterparts, shedding light on several key distinctions between the two groups. Among the stroke patient cohort, characterized by a mean age of 66.7 years and a majority of male participants, notable socioeconomic and lifestyle disparities emerged. Specifically, stroke patients exhibited a higher prevalence of lower household income, current smoking habits, and alcohol consumption compared to their counterparts without a history of stroke. Additionally, a concerning trend of reduced engagement in regular exercise was observed among stroke patients, alongside elevated metrics such as body mass index, blood pressure levels, fasting glucose, and total cholesterol, all contributing to a heightened Charlson Comorbidity Index (CCI) score.
Over the duration of the follow-up period, a striking disparity in the incidence probability of Parkinson’s disease (PD) emerged between stroke patients and their non-stroke counterparts, signifying a noteworthy association between stroke and PD risk. The adjusted hazard ratio (aHR) for PD in stroke patients was quantified at 1.67 (95% CI = 1.57–1.78) compared to individuals without a history of stroke, underscoring a substantially elevated risk among the stroke-afflicted population.
Furthermore, this heightened risk of PD was consistent across both disabled and non-disabled stroke patients, implying that disability status did not significantly alter the association between stroke and PD risk. However, it is worth noting that stroke patients with mild disability exhibited a particularly pronounced elevation in PD risk compared to those with severe disability, indicating a nuanced relationship between stroke severity and subsequent PD development.
The sensitivity analyses, incorporating a 1-year lag period, provided further validation of the heightened risk of PD among stroke patients, reaffirming the robustness of the initial findings. Despite a slight attenuation in risk beyond the lag period, the persistent elevation in PD risk underscores the imperative for vigilant monitoring and targeted interventions among stroke survivors, particularly in the immediate aftermath of stroke onset.
In summation, these comprehensive findings underscore the intricate interplay between stroke and PD risk, highlighting the imperative for heightened vigilance, tailored interventions, and ongoing surveillance to mitigate the potential burden of PD among stroke survivors, thereby enhancing overall patient outcomes and quality of life.
Conclusion
This study represents a pioneering effort in investigating the incidence of Parkinson’s disease (PD) among stroke patients, revealing a 1.7-fold higher risk of PD in individuals with a history of stroke compared to those without. Sensitivity analysis with a 1-year lag period provided further insight, suggesting a potential association between stroke and PD even after accounting for increased medical contact within the first year post-stroke.
The mechanism underlying PD development post-stroke involves cerebral ischemia-induced aggregation of alpha-synuclein (α-syn) and loss of dopaminergic neurons, supported by both animal and human studies. Shared risk factors such as age, hypertension, diabetes, and heart failure contribute to the onset of both stroke and PD, hinting at overlapping pathophysiology. Genetic factors also play a role, with common genes identified in stroke and PD patients.
Structural brain lesions resulting from stroke may lower the threshold for PD symptoms by compromising motor reserve, potentially explaining the higher incidence of PD in stroke patients. Interestingly, PD was more prevalent among stroke patients with mild disabilities, possibly due to underdiagnosis in those with severe disabilities, highlighting the importance of early screening and diagnosis.
Clinically, the co-occurrence of PD in stroke patients poses significant challenges, including prolonged hospitalization, increased morbidity, and mortality rates, as well as compromised rehabilitation outcomes. Early detection of PD symptoms in stroke patients is crucial for timely intervention and rehabilitation to maintain quality of life.
However, the study acknowledges several limitations, including the possibility of misdiagnosis and ascertainment bias, as well as the need for further research to validate findings across different ethnic groups. In conclusion, this study underscores the importance of understanding the association between stroke and PD and calls for continued investigation into their underlying mechanisms and clinical implications.
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