Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease

Abstract

ImportanceThe prodromal phase of Parkinson disease (PD) may last for more than 10 years. Recognition of the spectrum and occurrence of risk factors, comorbidities, and prodromal features of PD can increase understanding of the causes and development of the disease and help identify individuals at risk.ObjectiveTo identify the association of a subsequent diagnosis of PD with a range of risk factors and prodromal features, including lifestyle factors, comorbidities, and potential extracerebral manifestations of PD.Design, Setting, and ParticipantsThis was a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2011, and December 31, 2020. Included were patients with incident diagnosis of PD without a previous diagnosis of parkinsonism or dementia and controls matched 1:2 for age, sex, region, and earliest year of outpatient encounter.ExposuresExposures were selected based on previous systematic reviews, case-control and cohort studies reporting on risk factors, comorbidities, and prodromal features of PD.Main Outcomes and MeasuresPreviously postulated risk factors and prodromal features of PD, using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding.ResultsA total of 138 345 patients with incident PD (mean [SD] age, 75.1 [9.8] years; 73 720 male [53.3%]) and 276 690 matched controls (mean [SD] age, 75.1 (9.8) years; 147 440 male [53.3%]) were identified. Study participants were followed up for a mean (SD) of 6.0 (2.0) years. Consistent with previous reports, risk factors and prodromal features associated with PD included traumatic brain injury, odds ratio (OR), 1.62; 95% CI, 1.36-1.92; alcohol misuse, OR, 1.32; 95% CI, 1.21-1.44; hypertension, OR, 1.29; 95% CI, 1.26-1.31; anosmia, OR, 2.16; 95% CI, 1.59-2.93; and parasomnias (including RBD), OR, 1.62; 95% CI, 1.42-1.84. In addition, there were associations with restless legs syndrome (OR, 4.19; 95% CI, 3.91-4.50), sleep apnea (OR, 1.45; 95% CI, 1.37-1.54), epilepsy (OR, 2.26; 95% CI, 2.07-2.46), migraine (OR, 1.21; 95% CI, 1.12-1.29), bipolar disorder (OR, 3.81; 95% CI, 3.11-4.67), and schizophrenia (OR, 4.48; 95% CI, 3.82-5.25). The following diagnoses were also found to be associated with PD: sensory impairments beyond anosmia, such as hearing loss (OR, 1.14; 95% CI, 1.09-1.20) and changes of skin sensation (OR, 1.31; 95% CI, 1.21-1.43). There were also positive associations with skin disorders (eg, seborrheic dermatitis, OR, 1.30; 95% CI, 1.15-1.46; psoriasis, OR, 1.13; 95% CI, 1.05-1.21), gastrointestinal disorders (eg, gastroesophageal reflux, OR, 1.29; 95% CI, 1.25-1.33; gastritis, OR, 1.28; 95% CI, 1.24-1.33), conditions with a potential inflammatory component (eg, seronegative osteoarthritis, OR, 1.21; 95% CI, 1.03-1.43), and diabetes types 1 (OR, 1.32; 95% CI, 1.21-1.43) and 2 (OR, 1.24; 95% CI, 1.20-1.27). Associations even 5 to 10 years before diagnosis included tremor (odds ratio [OR], 4.49; 95% CI, 3.98-5.06), restless legs syndrome (OR, 3.73; 95% CI, 3.39-4.09), bipolar disorder (OR, 3.80; 95% CI, 2.82-5.14), and schizophrenia (OR, 4.00; 95% CI, 3.31-4.85).Conclusions and RelevanceResults of this case-control study suggest that the associations found between PD and certain risk factors, comorbidities, and prodromal symptoms in a representative population may reflect possible early extrastriatal and extracerebral pathology of PD. This may be due to shared genetic risk with PD, medication exposure, or direct causation, or represent pathophysiologically relevant factors contributing to the pathogenesis of PD.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study

“…A previous study by Stanković and colleagues found that 71% of early PD patients, classified as Hoehn and Yahr (H&Y) stage I, reported having autonomic symptoms (2). Autonomic dysfunction may also be a prodromal manifestation of PD, with early autonomic features predicting a faster rate of PD progression (3)(4)(5). Furthermore, pathological studies have shown the presence of alpha-synuclein deposition within the nuclei of autonomic plexi, which has been found to correlate with accelerated cell death in the autonomic nervous system (6,7).…”

Colonoscopy does not increase the risk of Parkinson’s disease

“…We found a higher risk of PD for one behavioral risk factor than for two or more behavioral risk factors. In general, previous studies have shown a positive association between alcohol abuse 42 and PD and traumatic brain injury 43 and PD, whereas there is a negative association between nicotine abuse and PD 36,44 . By combining risk factors with opposite effect directions, effect sizes of the index variable should be viewed with caution.…”

Association between Antiepileptic Drugs and Incident Parkinson’s Disease among Patients Followed in German Primary Care Practices

“…Associations between epilepsy and PD [ 3 , 4 ] and between restless legs syndrome and PD [ 15 , 16 ] have already been reported in the past. The prevalence of restless legs syndrome is increased in PD patients compared to the general population, and both epilepsy and restless legs syndrome have been reported as an early clinical feature of PD [ 16 , 17 ]. Furthermore, pain is a common non-motor symptom of PD, and neuropathy is increased in PD patients, including in the prodromal phase [ 7 , 18 , 19 ].…”