Risk Factors and Early Presentations of Parkinson Disease in Primary Care
JAMA Neurology:
Early and prodromal features of Parkinson disease (PD) have increasing relevance as the quest for potential disease-modifying therapies is expanding.
KEY TAKE-HOME MESSAGE
Question What are the prediagnostic manifestations of Parkinson disease (PD) presented in the primary care setting?
Findings This case-control study including 1055 individuals who developed PD over time noted signs and symptoms that occurred before diagnosis, with tremor and memory symptoms being the most prominent.
A strong association was found between PD and tremor (OR, 145.96) and memory symptoms within 2 years of diagnosis. The presence of previously described early nonmotor manifestations, including hypotension, constipation, and depression, was also confirmed. Two associations found were not well known previously: associations with epilepsy and hearing loss.
Several recognized prediagnostic features were replicated, including temporal associations between epilepsy and hearing loss with subsequent PD.
Meaning The findings of this study suggest there is a broad range of symptoms that people present in the primary care setting up to a decade before PD diagnosis.
This study presents much-needed data on the prediagnostic associations in underrepresented populations and identifies two new factors associated with PD diagnosis, namely, epilepsy and hearing loss.
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IMPORTANCE
Early features of Parkinson disease (PD) have been described through population-based studies that overrepresent White, affluent groups and may not be generalizable.
OBJECTIVE
To investigate the association between risk factors and prediagnostic presentations of PD in an ethnically diverse UK population with high socioeconomic deprivation but universal access to health care.
DESIGN, SETTING, AND PARTICIPANTS
A nested case-control study was conducted using electronic health care records on 1 016 277 individuals from primary care practices in East London to extract clinical information recorded between 1990 and February 6, 2018. The data were analyzed between September 3, 2020, and September 3, 2021. Individuals with a diagnosis of PD were compared with controls without PD or other major neurological conditions.
MAIN OUTCOMES AND MEASURES
A matched analysis (10 controls matched for each patient with PD according to age and sex) and an unmatched analysis (adjusted for age and sex) were undertaken using multivariable logistic regression to determine associations between risk factors and prediagnostic presentations to primary care with subsequent diagnosis of PD. Three time periods (<2, 2-<5, and 5-10 years before diagnosis) were analyzed separately and together.
RESULTS
Of 1 016 277 individuals included in the data set, 5699 were excluded and 1055 patients with PD and 1 009 523 controls were included in the analysis. Patients with PD were older than controls, and more were male. In the matched analysis (1055 individuals with PD and 10 550 controls), associations were found for tremor and memory symptoms less than 2 years before the PD diagnosis. The associations were also found up to 10 years before PD diagnosis for tremor and 5 years for memory symptoms. Among midlife risk factors, hypertension and type 2 diabetes (OR, 1.39; 95% CI, 1.19-1.62) were associated with subsequent diagnosis of PD. Associations with early nonmotor features, including hypotension, constipation, and depression, were also noted. Associations were found for epilepsy and hearing loss, which have not previously been well reported. These findings were replicated using data from the UK Biobank. No association with future PD diagnosis was found for ethnicity or deprivation index level.
CONCLUSIONS AND RELEVANCE
This study provides data suggesting that a range of comorbidities and symptoms are encountered in primary care settings before PD diagnosis in an ethnically diverse and deprived population. Novel temporal associations were observed for epilepsy and hearing loss with subsequent development of PD. The prominence of memory symptoms suggests an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally underrepresented groups.
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