Authors: Ignacio J. Posada MD, PhD, Julián Benito-León MD, PhD, Elan D. Louis MD, MSc, Rocío Trincado MA, Alberto Villarejo MD, María José Medrano MD, PhD, Félix Bermejo-Pareja MD, PhD
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Most studies of mortality in Parkinson's disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinson's disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population-based study in which Parkinson's disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinson's disease at baseline (1994-1995). Thirteen-year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow-up of 12.0 years (range, 0.04-14.8 years), including 66 of 81 subjects (81.5%) with Parkinson's disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinson's disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinson's disease (hazard ratio, 2.29; 95% confidence interval, 1.80-2.93; P < .001) versus subjects without Parkinson's disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinson's disease (hazard ratio, 1.75; 95% CI, 1.32-2.31, P < .001). In additional Cox models, Parkinson's disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40-4.90; P < .001). In this prospective population-based study, Parkinson's disease was an independent predictor of mortality in the elderly. Parkinson's disease patients with dementia had particularly high risks of mortality.
© 2011 Movement Disorder Society
Summary and review by Dr. Mariese Hely, MBBS, FRACP and Dr. Victor Fung, PhD, FRACP
The Study of Mortality from Parkinson's Disease - a Population-Based Prospective Study by Ignacio Posada and colleagues is part of the NEDICES study, a prospective, population based study in subjects aged 65 and over in Central Spain of the major age-associated neurological problems, including Parkinson's disease, essential tremor, stroke and dementia. This paper reports the risk of mortality from Parkinson's disease in their cohort at 13 years of follow-up.In the years 1994-1995, 5,262 people were entered into the study. Of these, 81 had Parkinson's disease at baseline, giving a prevalence of 1.5%. Of the 81 subjects with Parkinson's disease, 73% had their disease for between 1-9 years, 24% for 10-19 years and 4% for more than 20 years. The age of onset of Parkinson's disease ranged from 41-84 years, but the median age of onset of Parkinson's disease was 70 years. The majority had mild disease at enrolment: 61% had a Hoehn & Yahr stage of 1 or 2, 15% were Hoehn & Yahr stage 3, 20% were Hoehn & Yahr stage 4, and 5% were Hoehn & Yahr stage 5.
The two main strengths of this study are firstly, that the study was population rather than clinic based, therefore avoiding some potential sources of bias such as selection of patients with more severe disease, and secondly, that the diagnosis of Parkinson's disease in all cases was confirmed by a movement disorders neurologist. Dementia was diagnosed using DSM IV criteria. Date and cause of death were obtained from the national population register of Spain.
At baseline, the Parkinson's group were significantly older (77 years versus 74.3 years (p<0.001)), and were more likely to have dementia (16% versus 5.7%, (p< 0.001)) and depression (47.4% versus 25.4%, (p< 0.001)), but less likely to have cardiac disease (2.6% versus 10.3%, (p=0.03)).
At 13 years, 81.5% of the 81 Parkinson's disease subjects had died compared with 50.8% of the non-Parkinson's group. The risk of death was increased in the Parkinson's group (hazard ratio 1.75; 95.% CI 1.32-2.31; p< 0.001). The risk of mortality was particularly high in people with Parkinson's disease with dementia (adjusted hazard ratio 2.62; 95% CI 1.40-4.90), even when adjusted for other factors such as age and vascular risk. Risk of death was also increased with increasing age of disease onset, Hoehn & Yahr stage and disease duration. Parkinson's disease was stated as the cause of death in 18.2% of patients. In both the Parkinson's disease and the non-Parkinson's groups, cardio-vascular disease was the most frequently reported cause of death.
The hazard ratios reported in this study fall within the range of 1.5-2.5 found in previous studies. One could hypothesise that the risk of mortality from Parkinson's disease might be reduced if it develops later in life, as patients might succumb from other diseases before their Parkinson's disease has a chance to progress to severe stages. The data from this study argue otherwise. The key message from the NEDICES study is that in spite of modern therapy, Parkinson's disease remains an important independent risk factor of mortality in the elderly. Future studies that examine in more detail the mechanisms of increased mortality from Parkinson's disease are required to assist in designing therapeutic strategies to reduce this risk.
About Dr. Mariese Hely, MBBS, FRACP
Dr Mariese Hely is a Consultant Neurologist at the Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney Australia. She has a longstanding clinical and research interest in Parkinson's disease including being the primary researcher and author of a series of papers on the natural history of Parkinson's disease from the Sydney Multicentre Study.
About Dr. Victor Fung, PhD, FRACP
Dr Victor Fung is Clinical Associate Professor at Sydney Medical School, The University of Sydney and Director of the Movement Disorders Unit and Co-Director of the Parkinson's Disease and Movement Disorders Research Centre, Department of Neurology, Westmead Hospital. He is President of the Movement Disorder Society of Australia (MDSA) and serves on the International Executive Committee, Congress Scientific Program Committee, Education Committee, Bylaws Committee and Web Editorial Board of the International Movement Disorder Society (MDS). He is Secretary of the Asian & Oceanian Section of the MDS and has previously served on its Education Committee. He is on the Editorial Board of Basal Ganglia and previously Movement Disorders. He was the founding Chairperson of the MDSA Clinical Research and Trials Group from 2001-2007 and on the Management Board of Neuroscience Trials Australia from 2003-2007. He is a member of the Parkinson's Australia Scientific Committee and Parkinson's NSW Advisory Board.