Researchers said 2 additional warning signs of Parkinson disease (PD) may be the onset of hearing loss and epilepsy years before the hallmark features of the disease appear, adding new weight to the idea that the neurological condition has a long prodromal phase.
The study was carried out in London, where everyone has access to universal health care and where investigators were able to delineate which manifestations and issues led patients to visit primary care in the decade before receiving a PD diagnosis.
Moreover, one of the main strengths of the study, published in JAMA Neurology, is that it was carried out in East London, a very diverse area with a high rate of poverty and socioeconomic deprivation compared with the rest of the United Kingdom.1 The researchers replicated their findings from primary care databases with data from the UK Biobank.
The majority of PD studies are conducted with data on patients who are White and from higher socioeconomic levels. By contrast, the population in this study was quite different. Black, South Asian, and Chinese; other; and mixed ethnic groups make up about 45% of residents in East London compared with 14% in the rest of the United Kingdom. In addition, East London has one of the highest unemployment rates (6.7%), and most patients (80%) rank in the lowest 2 quintiles of national wealth.
The nested case-control study was conducted with extracted clinical information from electronic medical records on more than 1 million patients from primary care practices in East London, with visits recorded between 1990 and February 6, 2018. Individuals with a diagnosis of PD were compared with controls without PD or other major neurological conditions, and analysis occurred between September 3, 2020, and September 3, 2021.
Investigators matched 10 healthy controls to each patient with PD by age and sex and conducted an unmatched analysis, which was adjusted for age and sex, using multivariable logistic regression to determine associations between risk factors and prediagnostic presentations to primary care with subsequent diagnosis of PD.
The investigators examined what patients went to primary care clinics in the years before a PD diagnosis, stratified into 3 time periods: less than 2, 2 to less than 5, and 5 to 10 years before diagnosis; the time periods were analyzed separately and together.
After exclusions, 1055 patients with PD and 1,009,523 controls were included in the analysis.
Patients with PD were older than controls (mean [SD], 72.9 [11.3] vs 40.3 [15.2] years), and more were male (632 [59.9%] vs 516,862 [51.2%]).
The matched analysis of 1055 individuals with PD and 10,550 controls found that less than 2 years before the diagnosis, patients with PD were more likely to visit their physician for complaints of tremor (odds ratio [OR], 145.96; 95% CI, 90.55-235.28) and memory problems (OR, 8.60; 95% CI, 5.91-12.49). Memory problems were also seen up to 5 years before a PD diagnosis but not beyond that.
Those associations held true for up to 10 years for patients seeking care for tremor and 5 years for memory symptoms.
Other findings significant for a later PD diagnosis included:
Other findings revealed that patients going to a physician within 2 years of their PD diagnosis with complaints of depression, anxiety, fatigue, and insomnia had about 2- to 4-fold higher odds of the disease. Pain factored in as well, with visits for shoulder pain linked with a doubling of the odds of PD diagnosis up to 5 years before diagnosis.
Ethnicity and poverty level were not linked with a later diagnosis, however.
The findings regarding epilepsy (OR, 2.50; 95% CI, 1.63-3.83) and hearing loss (OR, 1.66; 95% CI, 1.06-2.58) are novel, said the investigators, who replicated their findings using data from the UK Biobank.
Epilepsy was linked with later PD across all time periods. Hearing loss was linked with subsequent PD when found less than 2 years or 2 to 5 years prior to a PD diagnosis.
Until now, only early information from smaller studies was available to suggest that epilepsy and hearing loss might be linked with PD, which prompted the inclusion of those conditions in this study.
The authors said their's is the first study focusing on the prediagnostic phase of PD in a diverse population with universal access to health care.
In an accompanying editorial, the authors called this study “an important step in furthering early PD recognition and its implications for access to current pharmacologic and nonpharmacologic therapies and future disease-modifying treatments.” 2
1. Simonet C, Bestwick J, Jitlal M, et al. Assessment of risk factors and early presentations of Parkinson disease in primary care in a diverse UK population. JAMA Neurol. Published online March 7, 2022. doi:10.1001/jamaneurol.2022.0003
2. Patel B, Chiu S, Armstrong MJ. Identifying Parkinson risk markers in primary care—old associations and new insights. JAMA Neurol. Published online March 7, 2022. doi:10.1001/jamaneurol.2021.5542