Abstract
Abstract : This is a final report for a 10 year project (7/1/1999-8/31/2008). The goal of this epidemiologic and neuropathologic research program was to determine neurotoxic and preventive/ameliorative risk factors for Parkinson's disease (PD). Results related to prediction of incident PD from the Honolulu-Asia Aging Study (HAAS) supported by this project were as follows: coffee drinking may be protective against PD, milk consumption is associated with an increased risk of PD, Low LDL cholesterol is a predictor of PD among men aged 71-75. Increased triceps skinfold thickness, constipation, excessive daytime sleepiness, and olfactory dysfunction, are indicators that may precede the motor syndrome by years. Using neurpathological endpoints: olfactory dysfunction, constipation, and increased reaction predict incidental Lewy bodies. The Braak staging system for Lewy pathology is supported by evaluation of the HAAS autopsy series. One-third of elderly men without PD or dementia with Lewy bodies (DLB) have Lewy pathology in the olfactory bulb. Several preclinical indicators of PD are associated with this stage of synuclein deposition. Lewy pathology in the olfactory bulb is also associated with decreased neuron density in the substantia nigra. These findings indicate that several of the preclinical indicators of Parkinson's disease are expressed very early in the process of synuclein deposition and that neuron density in the substantia nigra also begins very early in this process. Genetic studies in collaboration with the Parkinson's institute noted an association of a polymorphism of the MDR1 transporter gene with PD. Analysis of frozen brain samples for organochlorines indicate that several of the organochlorines are detected more frequently in brains of men who also had Lewy bodies or Alzheimer changes at death. The identification of early markers for PD and susceptibility genes could identify individuals at high risk for the development of PD.
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