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The Rotterdam Study

Lonneke M. L. de Lau, MD; Peter J. Koudstaal, MD, PhD; Albert Hofman, MD, PhD; Monique M. B. Breteler, MD, PhD

Arch Neurol. 2006;63:362-365. Published online January 9, 2006 (doi:10.1001/archneur.63.3.noc50312).

Background  Neuronal degeneration and dopamine loss in the preclinical phase of Parkinson disease may produce subtle complaints before clinically recognizable symptoms emerge.

Objective  To examine whether subjective complaints of stiffness, slowness, tremors, or postural imbalance in persons without clinical signs of parkinsonism are related to an increased risk of future Parkinson disease.

Design  Population-based cohort study. We recorded subjective complaints of stiffness, slowness of movement, tremors, falling, or a feeling of imbalance in a standardized interview of 6038 participants without dementia in whom no parkinsonian signs were found on physical examination at baseline, and we studied them prospectively for the occurrence of incident Parkinson disease.

Setting  General population.

Participants  A total of 6038 participants who were free of dementia and parkinsonian signs.

Main Outcome Measures  Incident Parkinson disease. Participants were examined in person both at baseline (January 1990–June 1993) and at 2 follow-up visits (September 1993–December 1994 and April 1997–December 1999), and the cohort was continuously monitored through computerized linkage of the study database to general practitioners' medical records. We analyzed the data using Cox proportional hazards regression models.

Results  Participants who reported stiffness, tremors, or imbalance at baseline had a significantly increased risk of developing Parkinson disease during follow-up (for stiffness, hazard ratio, 2.11; 95% confidence interval, 1.25-3.55; P = .005; for tremors, hazard ratio, 2.09; 95% confidence interval, 1.12-3.90; P = .002; and for imbalance, hazard ratio, 3.47; 95% confidence interval, 1.69-7.00; P = .001).

Conclusions  Subjective complaints of stiffness, tremors, and imbalance are associated with an increased risk of future Parkinson disease and may reflect early effects of dopamine shortage, even when standard neurological testing cannot yet demonstrate any motor symptoms.

Author Affiliations: Departments of Neurology (Drs de Lau and Koudstaal) and Epidemiology and Biostatistics (Drs de Lau, Hofman, and Breteler), Erasmus Medical Center, Rotterdam, the Netherlands.

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