The influence of age and gender on motor and non-motor features of early Parkinson's disease: Initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort
Introduction
There is a growing recognition that Parkinson disease (PD) has phenotypic heterogeneity [1] in its motor and non-motor manifestations [2]. Age and gender are two basic characteristics that may influence disease phenotype, either through disease-independent factors or differences in underlying pathology. One therefore wants to examine age and gender related differences in a large incident cohort of patients with detailed phenotypic data.
Oxford Parkinson Disease Center (OPDC, http://opdc.medsci.ox.ac.uk) was established in 2009 with funding from the Parkinson UK Monument Discovery Award and brings together world-leaders in clinical neurology, neuroepidemiology, neuroimaging, proteomics, genomics, molecular genetics, transgenic PD models, neuropharmacology, neurophysiology and neuropathology. The OPDC cohort is a prospective, longitudinal study that has recruited patients with early idiopathic Parkinson Disease, healthy controls and participants at risk of PD. We present an analysis of age and gender effects on the PD phenotype with an overview of the study protocol in our cohort.
Section snippets
Participants
Study participants are recruited from neurology clinics across the Thames Valley area covering a population of 2.4 million. Participating centers include: Oxford, Reading, Newbury, Wexham Park, High Wycombe, Aylesbury, Milton Keynes, Kettering, Northampton, Banbury and Swindon. Neurologists, PD nurses, geriatricians and GP's from participating hospitals are asked to identify all idiopathic PD cases who were diagnosed within the last three years according to the UK PD Brain Bank criteria
Results
In the analyzed period, 624 PD patients agreed to take part in our study, making up 57% of all approached subjects. Non-participants were significantly older than participants (mean (SD), age 73.0 (10.6) years, p < 0.001), but with no gender differences. Additionally, 176 healthy controls (HC) were recruited into the study in the above period.
Discussion
In order to compare characteristics of our cohort with other large studies we performed a pubmed.com search which yielded 59 publications describing 35 cohorts of PD patients (Supplemental Table 4). Eight of those focused on patients with early stage disease within 4 years of diagnosis/onset (bold highlight). The average age of those patients was slightly lower than in our cohort with the ParkWest [3] cohort being most similar. The gender composition was comparable to our group while the
Age effect
The effect of age on clinical phenotype was suggestive of increased severity in older patients. The performance was worse on motor indices (total UPDRS-III and subscores, H&Y, peg-board, get-up-and-go) and non-motor scales (cognition, anxiety, constipation, urinary and erectile symptoms). Those effects cannot be attributed to medication dose (LEDD increasing with age), responsiveness to medication or disease duration (similar across strata). Later diagnosis in elderly subjects does not play a
Gender effect
A complex set of differences emerged from the comparison of gender-related phenotypes. In terms of motor features, a gradient of severity across body areas was identified, whereby men, compared to women, had much more advanced symptoms in the face and neck, with lesser difference in the arms and equal severity in the legs. In turn, women showed greater severity on postural scores. Importantly, the upper body symptoms differed both on examination and on patient-reported measures while
Strengths and limitations
A major limitation of our study is its cross-sectional nature, which may bias some variables through retrospective reporting. However, longitudinal data will gradually become available as patients come to follow-up. Another potential weakness of our analyses is that effects of age and gender were investigated in univariate comparisons. Our goal here was to provide a broad overview of symptoms in the early stage of PD and to identify areas of interest for further study. Hence, more detailed and
Conclusions
Our results confirm that age is a strong predictor of disease severity even after taking into account disease duration. Gender-related motor phenotype can be defined by a vertical split into more symmetrical upper-body disease in men and postural disease in women. Amongst the non-motor symptoms, men are more cognitively impaired and have higher rate of RBD than women. Future research is needed to establish whether the two genders may have different predictive value for disease progression.
Funding
This study was funded by the Monument Trust Discovery Award from Parkinson's UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, and the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Ethical approval
Berkshire Research Ethics Committee.
Disclosures
Dr. Konrad Szewczyk-Krolikowski has received research support from Parkinson's UK.
Dr. Paul Tomlinson has received research support from Parkinson's UK.
Dr. Kannan Nithi does not declare any conflict of interests.
Dr. Richard Wade-Martins has received research support from Parkinson's UK.
Dr. Kevin Talbot has received research support from Parkinson's UK.
Dr. Yoav Ben-Shlomo has received research support from Parkinson's UK.
Dr. Michele Hu is part-funded by the National Institute for Health Research
Acknowledgments
We thank all the participants, nurses and doctors who have helped identify and assess subjects for the OPDC-D cohort, Tim Bradford and Scott Roger for setting up the database and Parkinson's UK.
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