VANCOUVER—Patients may have impairments in their daily activities six years before they receive a diagnosis of Parkinson’s disease, according to an analysis presented at the 68th Annual Meeting of the American Academy of Neurology. These problems typically involve instrumental activities, which require motor and nonmotor skills. Subtle motor and cognitive deficits also may be observable six years before diagnosis. As the time of diagnosis approaches, additional motor symptoms arise, and patients report symptoms of anxiety and depression more frequently than people who do not develop Parkinson’s disease, said Sirwan Darweesh, MD, of the Erasmus MC University Medical Center in Rotterdam, the Netherlands. In addition, patients’ problems in daily functioning begin to affect basic activities.
Sirwan Darweesh, MD
Among researchers, interest in defining earlier stages of Parkinson’s disease is increasing, under the assumption that it may enable effective neuroprotection. Dr. Darweesh and colleagues conducted a nested case–control study within the population-based Rotterdam Study. The latter study was initiated in 1990 among inhabitants of a district of Rotterdam. All persons age 55 or older were invited to participate. Dr. Darweesh and colleagues excluded people with Parkinson’s disease at the time of enrollment from their analyses.
Approximately 8,000 people (about 80% of the eligible population) participated in the study. Individuals who did not participate tended to be slightly older and to have more locomotor diseases and more cardiovascular diseases.
At baseline, participants underwent a battery of assessments for potential prediagnostic features of Parkinson’s disease. The tests represented the three broad categories of activities of daily living, motor features, and nonmotor features. The investigators also assessed symptoms of depression and anxiety with the Center for Epidemiologic Studies Depression Scale and the Hospital Anxiety and Depression Scale. These assessments were repeated every four years.
In addition, the researchers evaluated whether participants had developed Parkinson’s disease during follow-up. Research physicians conducted repeated in person examinations and had complete access to participants’ medical files, which included diagnostic codes, specialist letters, and free text entries by neurologists and other physicians.
To identify differences between prediagnostic patients with Parkinson’s disease and controls, Dr. Darweesh and colleagues matched every person with incident Parkinson’s disease with 15 controls, based on age and sex. They analyzed the data to determine when prediagnostic features differed significantly between cases and controls during the prediagnostic period. In all, 107 people (approximately 50% women) developed incident Parkinson’s disease at a mean age of 77.
Movement and Postural Problems Emerged
At six years before Parkinson’s disease diagnosis, prediagnostic patients reported problems with daily activities, specifically instrumental activities such as traveling, more frequently than controls did. At about three years before diagnosis, problems in daily functioning extended to basic tasks such as eating, said Dr. Darweesh.
At about five to six years before diagnosis, prediagnostic patients showed signs of hypokinesia, bradykinesia, or tremor more frequently than controls did. In the last few years before diagnosis, patients also showed signs of cogwheel rigidity, postural abnormality, and postural imbalance more frequently than controls did.
When the investigators examined nonmotor features, they found that at about five years before diagnosis, patients with Parkinson’s disease already had significantly lower Mini-Mental State Examination scores than controls did. In the years before diagnosis, patients were also more likely to report anxiety symptoms and depressive symptoms than controls were. During follow-up, the researchers found that patients with Parkinson’s disease used laxatives more frequently than controls did, although differences only became significant in the last few years before diagnosis. “We believe that these data add important information to our knowledge of prediagnostic Parkinson’s disease,” said Dr. Darweesh. “We hope that these data can contribute to a better understanding of how to define earlier stages of this disease.”
—Erik Greb