MIAMI BEACH — Widespread screening for early Parkinson's disease with olfactory testing followed by neurologic imaging holds promise but is not yet practical, based on studies that have revealed the limitations of each method.
Olfactory impairment is common enough in premotor Parkinson's disease that some researchers propose using it as an early predictor of risk (Ann. Neurol. 2008;63:167–73).
However, olfactory testing has not garnered widespread adoption because it lacks sufficient specificity for population-based screening, Dr. Henk W. Berendse said at the World Federation of Neurology World Congress on Parkinson's Disease and Related Disorders.
He and others have proposed coupling olfactory testing with highly specific brain imaging, such as dopamine transporter single photon emission computed tomography (DAT SPECT).
There is a catch, though. The imaging would have to be done in a large number of individuals, many of whom would not develop Parkinson's disease, said Dr. Berendse, head of the movement disorders service at the VU University Medical Centre in Amsterdam.
In a subsequent presentation at the meeting, Dr. Andrew D. Siderowf of the department of neurology at Pennsylvania Hospital in Philadelphia called population screening for Parkinson's disease a “numbers game.” The incidence of Parkinson's disease is low, so the number of potentially identifiable cases in a population at any given time also is low, he said.
In 2005, the worldwide prevalence of the disease was estimated to be between 4.1 million and 4.6 million (Neurology 2007;68:384–6).
Dr. Berendse calculated that “If you expect to detect 125 patients in the premotor phase [of Parkinson's disease], somewhere between 1,000 and 7,000 individuals would have to undergo SPECT scans. Assuming a 10% prevalence of hyposmia, we would need to screen 70,000 individuals.” He based the 10% prevalence of hyposmia on the results of a study he coauthored that screened 361 asymptomatic, 50- to 75-year-old relatives of patients who had idiopathic Parkinson's disease. All of the relatives underwent olfactory testing, and the 40 who tested positive also underwent serial
He and his colleagues recently published the 5-year data for this cohort (J. Neurol. Neurosurg. Psychiatry 2009 Dec. 3 [doi:10.1136/jnnp.2009.183715
Those two studies support use of two-step olfactory and SPECT scanning in first-degree relatives because all of the five hyposmic individuals who developed Parkinson's disease had an abnormal baseline SPECT scan.
Dr. Siderowf said he remained optimistic about screening first-degree relatives of people with Parkinson's disease as a higher-risk group even though widespread screening would be cost-prohibitive. “The numbers start to look really good” when two-stage screening is considered for first-degree relatives, particularly those with multiple risk factors, he said.
However, he noted that access to DAT SPECT is restricted. It is costly and not commercially available in the United States.
In addition to DAT SPECT, researchers have proposed other imaging modalities to follow olfactory testing. For example, German researchers assessed transcranial sonography and assessed patients at 4 years (Mov. Disord. 2007;22:839–42).
“So far, transcranial sonography does not seem to be the way to go,” Dr. Berendse said. “Two patients who progressed to Parkinson's disease did not have initial transcranial abnormalities, for example, but more studies are on the way.”
Dr. Siderowf said the optimal screening strategy remains unknown. “Not only do these tests need to be used, but they have to be used repeatedly. What is the optimal screening frequency? The time at which imaging becomes abnormal varies—some say 5 years.”
Dr. Berendse said that ideally, he would like to find a noninvasive marker of early Parkinson's disease risk with a higher specificity than olfactory dysfunction and a less costly second screening step.
Neither Dr. Berendse nor Dr. Siderowf had relevant financial disclosures.