Pre-motor features of Parkinson's disease: the Honolulu-Asia Aging Study experience

The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men, born 1900-1919. Beginning in 1965, environmental, life-style, and physical characteristics, including many features associated with pre-motor Parkinson's disease (PD), were ascertained at examinations over 40 years. Men with clinical PD were identified and final diagnosis was made by consensus of two neurologists. Additionally, brain autopsies have been sought since 1991 allowing use of incidental Lewy bodies and neuronal loss in the substantia nigra (SN) and locus coeruleus (LC) as additional endpoints for the PD process. Impaired olfaction, constipation, slow reaction time, excessive daytime sleepiness, and impaired executive function were all associated with future development of PD and/or with increased likelihood of either incidental Lewy bodies or neuronal loss in the SN or LC. Compared with persons without any, those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD. While low specificity and positive predictive value limit the use of these clinical features alone to identify pre-motor PD, these methods may be useful for identifying a high risk group for participation in intervention trials aimed at preventing or slowing the progression of PD.