Risk factors, early presentations, and clinical markers of Parkinson’s disease in Primary Care in a diverse UK population
Authors: Simonet Cristina , Bestwick Jonathan , Jitlal Mark , Ben-Joseph Aaron , Marshall Charles R. , Dobson Ruth , Marrium Soha , Robson John , Lees Andrew J. , Giovannoni Gavin , Cuzick Jack , Schrag Anette , Noyce Alastair J. 
Published: October 2021

AbstractImportancePredictors of future Parkinson’s disease (PD) have been suggested through population-based studies, but these studies over-represent white, affluent groups and may not be generalisable.ObjectiveTo investigate the association between risk factors and pre-diagnostic presentations of PD in a uniquely diverse UK population, with universal access to health care.Design, Setting, and ParticipantsA case-control study was conducted in East London, using primary care health records.Main outcomes and MeasuresLogistic regression was used to determine associations between risk factors and pre-diagnostic presentations of PD with final diagnosis. Three periods (recorded <2 years, 2-5 years, and 5-10 years prior to diagnosis) were analysed.ResultsPrimary care records were available for 1,055 patients with PD and 1,009,523 controls. The strongest associations were found for tremor (OR, 181.69; 95% CI, 151.91-217.31) and ‘memory complaints’ (OR, 9.84; 95% CI, 7.39-13.11), <2 years before PD diagnosis. However, associations for both complaints persisted up to 10 years prior to PD diagnosis. Shoulder pain was more common in those who developed PD, emerging 5 to 10 years prior to diagnosis (OR, 2.54; 95% CI, 1.77-3.65), and may be a surrogate marker for rigidity. Epilepsy showed a strongest association with subsequent PD (OR, 5.14; 95% CI, 1.26-21.0), and associations were also found for hypertension (OR, 1.71; 95% CI, 1.34-2.17) and type 2 diabetes (OR, 1.57; 95% CI, 1.31-1.87) 5 to 10 years before diagnosis. We replicated several known associations with early non motor features including hypotension, constipation, and depression. A weak but novel association was observed with prodromal hearing loss and subsequent PD, which appeared up to 10 years prior to diagnosis. No associations with future PD diagnosis were found for ethnicity or deprivation index.Conclusions and relevanceThis study provides further evidence that a range of comorbidities and pre-diagnostic presentations are encountered in primary care prior to PD diagnosis, but for the first time in such a diverse and deprived population. Convincing temporal associations were observed for epilepsy and hearing loss with subsequent PD. The predominance of ‘memory symptoms’ hints at an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally under-represented groups.Key pointsQuestionWhat are the pre-diagnostic manifestations of Parkinson’s disease (PD) that present to primary care in a diverse and deprived population with universal access?FindingsTremor and ‘memory symptoms’ were reported up to 10 years before diagnosis and were most strongly associated with PD. Several recognised pre-diagnostic features were replicated, but novel temporal associations between epilepsy and hearing loss with subsequent PD were observed.MeaningThe range of symptoms that cause people to present to primary care, up to a decade before PD diagnosis, are broad. The strength of association, relative importance and interpretation of prodromal features may vary according to the population studied.