A study designed to assess how well certain tests predict decline in early Parkinson disease (PD) patients has turned up a surprising correlation: PD patients with higher education start treatment sooner than other patients.
This finding, reported online on July 13 in advance of the print edition of Archives of Neurology, may seem counterintuitive, according to lead author Sotirios A. Parashos, MD, PhD, of the Struthers Parkinson's Center in Eden Valley, MN. People with less education are probably more likely to do physical labor, he said, which would be disrupted by the tremors and other movement disorders caused by PD.
But he does not believe that education somehow accelerates decline in PD, or that this finding is a statistical anomaly. Rather, since the study used the time to symptomatic treatment as a measure of decline, Dr. Parashos suspects that people with higher education may have a greater desire for symptomatic treatment. A mild hand tremor, for example, may cause little disability, but a lawyer, physician, or manager may fear that such a sign of infirmity could compromise the impression they make on others.
Also, people with higher education are more likely to be better informed about their condition, according to Dr. Parashos, and therefore play a more active role in making decisions about their own care. In a 2002 paper in the Mayo Clinic Proceedings, he reported that people with higher education are more likely to utilize medical services than their less-educated counterparts.
Whatever the explanation, Dr. Parashos believes these results demonstrate that education has a complex relationship with PD outcomes.
“Education may have nothing to do with the disease itself,” he said, “but this study tells us that you cannot ignore level of education when you do studies that use the time to symptomatic treatment as the outcome. Education has an effect. We don't know why it has an effect, but it has an independent effect that could confound your outcome, so you have to enter it into your model.”
Further study of this finding is warranted, Dr. Parashos added, because level of education may have “a significant but as yet unrecognized effect on treatment patterns, with consequences for the quality of care.”
STUDY PROTOCOLS, RESULTS
The study set out to assess the predictive value of common tests used to determine impairment, disability, and quality of life for early PD patients, including the Unified Parkinson Disease Rating Scale (UPDRS), the Modified Rankin Scale, the Schwab and England Activities of Daily Living Scale, the Total Functional Capacity Scale, the 39-item Parkinson Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale. Dr. Parashos also collected data on the patients' sex, age, race and ethnicity, disease duration, and occupational status, as well as on their level of education.
Within 12 months nearly half of the 413 study participants reached the endpoint — they were receiving treatment to relieve the symptoms of their PD — and as expected, the higher their baseline impairment as determined by the various tests, the sooner they progressed to needing symptomatic treatment.
But higher level of education also emerged as an independent variable predicting a more rapid progression to the need for such treatment. Also, the widely used PDQ-39 displayed little predictive power. “That means either that quality of life is not a significant factor in deciding when to start treatment, which intuitively doesn't make sense, or that the PDQ-39 is not very sensitive in the early stages of the disease,” Dr. Parashos said.
Cynthia Comella, MD, professor of neurological sciences at Rush University Medical Center in Chicago, called the study “excellent” because “it verifies to some degree what we see in clinical practice, which is that it's motor impairment and disability as measured by activities of daily living that are primarily involved in determining when one gives symptomatic treatment.”
She was surprised by the finding that depression did not play a significant role in predicting progression to symptomatic treatment, since that correlation was found in another study, but she thought that differences in methods and analysis may account for the different findings. She considers the findings about level of education to be “right on target.”
“Their explanation that those with a higher educational level may access health care in a different way is an intriguing one,” she said.
Others expressed greater reservations about that finding.
“It could be an important variable or a by-chance variable,” said Rajesh Pahwa, MD, Laverne and Joyce Rider Professor of Neurology and director of the Parkinson Disease and Movement Disorder Center at the University of Kansas Medical Center. “For example, manual laborers who may have less education might be doing more physical tasks, and therefore exercising more, so they are experiencing less disability. That's just a hypothesis I'm putting forward, but it could be an interesting variable. Also, could the physician's perception be a factor? Might we subconsciously choose to treat a patient who is a physician, for example, earlier than we would a farmer? Might we say to ourselves, OK, you farm, so you don't need that much treatment control. It could be physician bias.”
Also, someone with less education working at a manual job may be more willing to accept disability and retirement, according to Anthony E. Lang, MD, director of the Morton and Gloria Shulman Movement Disorders Centre at Toronto Western Hospital and the Division of Neurology at the University of Toronto.
“But those in a high-functioning managerial position who want to continue working may believe that having a tremor might compromise their effectiveness,” he said.
Dr. Lang does not expect these results to have any effect on the ongoing debate about when and how to start symptomatic treatment, which he discussed in a supplement to Neurology in February. He wrote that levodopa, which replenishes the dopamine lacking in PD patients, seems to increase the longevity of PD patients, but it causes motor complications more frequently than alternative treatments. Dopamine agonists, which activate dopamine receptors even in the absence of endogenous dopamine and result in less dyskinesia, cause other adverse effects, including leg edema, somnolence, and impulse control disorders more frequently than levodopa, and are generally clinically less effective than levodopa, he said.
But treatment strategies may soon change, Dr. Lang added, depending on the results of two ongoing studies. One, the ADAGIO trial, evaluated the effects of rasagiline (Azilect) in PD in a delayed start design. Although still unpublished, this trial showed a benefit to earlier treatment with 1.0 mg of rasagiline compared to placebo, followed by the delayed introduction of rasagiline. It is still uncertain whether this result was related to a unique disease-modifying effect of rasagiline, or to the earlier use of a drug with symptomatic effects that lessen the disability of PD.
A similarly designed involving pramipexole (Mirapex), is expected to produce results by the end of the year.
The results “could further the argument that early symptomatic treatment modifies the disease process in some way,” Dr. Lang said. “If we find that these drugs influence disability scores in a way that is not reproduced by the later introduction of the same agent following a treatment delay, that might further support starting treatment sooner rather than later.”