WASHINGTON – The presence of constipation, poor olfaction, slow reaction time, and excessive daytime sleepiness in any combination strongly suggests the presence of preclinical Parkinson's disease, according to findings from the ongoing Honolulu-Asia Aging Study presented at the World Parkinson Congress.
Dr. G. Webster Ross of the University of Hawaii in Honolulu and his colleagues on the Honolulu-Asia Aging Study (HAAS) have been able to assess the relationship between these four factors and, not only Parkinson's disease (PD), but the presence of Lewy bodies in the brain as well.
HAAS began in 1965 as the Honolulu Heart Program, a prospective study of heart disease and stroke that followed a cohort of 8,000 Japanese-American men (all born between 1900 and 1919). The aging component of the study began in 1991 with case findings for dementia and Parkinson's disease. The researchers have continued to identify cases through examinations in 1994, 1997, 1999, 2001, and 2003. The researchers also have continued surveillance of hospital death records in order to confirm diagnoses. Preclinical determinants were assessed prior to the diagnosis of PD.
An autopsy study began in 1991. Since then, the researchers have been examining stained sections of the substantia nigra, the locus coeruleus, and the amygdala for the presence of Lewy bodies. If Lewy bodies are found in any of these three areas, the researchers then look for cortical Lewy bodies as well.
“We have been able to identify those individuals with incidental Lewy bodies–that is, those that occur in decedents without dementia or Parkinson's disease,” Dr. Ross said. “We have used this incidental Lewy body stage as an … end point in addition to Parkinson's disease, with the idea that if we find risk factors or predictors of both of these conditions that it's plausible evidence that [the risk factors] probably are truly associated with the disease or with the underlying pathophysiologic process.”
The researchers recently looked at how combinations of four factors–excessive daytime sleepiness (EDS), olfactory dysfunction, constipation, and slow reaction time–might be related to the incidence of PD. For constipation and slow reaction time, they found that the incidence of PD was 1 in 1,370 for those with neither symptom, 13 in 1,402 for those with one symptom, and 4 in 82 for those with both symptoms.
They also looked at the combination of EDS and olfactory dysfunction. The incidence of Parkinson's was 1 in 370 for those with neither symptom, 5 in 452 for those with one symptom, and 2 in 32 for those with both symptoms.
They then looked at the combination of EDS, olfactory dysfunction, and slow reaction time. The incidence of PD was 1 in 298 for those with no symptoms, 10 in 1,151 for those with one symptom, 5 in 378 for those with two symptoms, and 2 in 27 for those with all three symptoms.
Individually, all four factors have been associated with Parkinson's disease. The associations are detailed in the following paragraphs:
▸ Excessive daytime sleepiness. EDS was assessed through a questionnaire that HAAS researchers sent to cohorts in 1991. The researchers found that 23% of PD patients had EDS, compared with 8% of those who did not have PD. “The incidence of Parkinson's disease among those with excessive daytime sleepiness is about 2.5 times the incidence of individuals without excessive daytime sleepiness,” Dr. Ross said.
▸ Olfactory dysfunction. Olfactory dysfunction is common among PD patients and is known to occur early in the disease process. Olfactory dysfunction also correlates with dopamine transporter density in early Parkinson's on single photon emission CT imaging. Olfaction was assessed at the 1991 and 1994 examinations of the HAAS cohort using the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability. “As odor identification improves to the highest tertile, the incidence of Parkinson's disease declines,” said Dr. Ross. Likewise, as odor identification improved among patients with incidental Lewy bodies, the percentage with Lewy bodies in the substantia nigra or the locus coeruleus went down significantly.
▸ Constipation. Constipation occurs in an estimated 80% of PD patients and appears to be independent of age, medication use, or level of physical activity. There is a loss of dopaminergic neurons in the colon, and Lewy bodies in the myenteric plexus, in patients with PD. Constipation was assessed in the HAAS cohort with a question about bowel movement frequency at midlife (1971) and again in 1991. Dr. Ross and his colleagues found that the incidence of Parkinson's disease was highest in men who reported less than one bowel movement per day, and that the incidence declined as the number of bowel movements per day increased.