Research Projects - Neurodegenerative Diseases
Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, impact the lives of millions and pose a growing public health challenge, particularly as more people approach older age. PHREI is part of a national collaborative network that examines possible factors contributing to neurodegenerative diseases.
The Association of Brain Organochlorine Levels with Pathologic Markers of Parkinson's Disease
The goal of this epidemiologic and neuropathologic program is to determine neurotoxic and preventive/ameliorative risk factors for Parkinson’s disease (PD), Parkinsonism, and other neurodegenerative conditions. The research involves analysis of existing data in the Honolulu-Asia Aging Study (HAAS) to examine the relationship of brain organochlorine levels with substantia nigra neuron density and striatal dopamine and dopamine metabolite levels.
A component of this project is to identify risk factors for PD and Parkinsonism and to confirm previous reports of an association between pesticide exposure and PD by examining the role of exposure to neurotoxins in occupations on sugar or pineapple plantations where pesticides or herbicides are used. The study also looks at self reported exposures to pesticides, metals, and other chemicals.
Results indicate that several organochlorines are detected more frequently in brains of men who also had Parkinson at death. The organochlorine exposure in most of these brains took place as long as 30 years ago. We are beginning to examine the association of these levels with clinical endpoints (Parkinson’s disease, Parkinsonism, Alzheimer’s disease, cognitive impairment) and continuing our evaluation of pathologically-detectable endpoints.
Risk Factors for Pathologic Markers of Parkinson's Disease Study
This study attempts to quantify two neuropathologic markers of specific neurodegenerative processes - neuronal loss in the substantia nigra and diminished striatal dopamine levels in the brains of Japanese-American male decedents who were participants in the Honolulu Heart Program/Honolulu Asia Aging Study. Substantia nigra neuron density and striatal dopamine levels are used as endpoints that represent the pathological processes underlying Parkinson's disease to evaluate potential risk and protective factors that influence these processes.
Parkinson’s Disease Clinical Trials
PHREI is a clinical center for two ongoing clinical trials examing medications that may slow the progression of Parkinson's disease. The first is a multicenter, double-blind , placebo-controlled, trial designed to determine whether creatine may slow disease progression. The second is another multicenter trial to assess whether isradipine, a commonly used blood pressure medication, has potential to slow Parkinson's disease progression and to determine toxicity and tolerability of this medcication in Parkinson's disease patients.
In addition, PHREI investigators collaborate with the Honolulu Asia Aging Study (HAAS) at Kuakini Medical Center under the direction of Dr. Lon White, to study diseases associated with aging such as Alzheimer’s disease, vascular dementia, and Parkinson’s disease. Several PHREI studies are complimentary to the HAAS and involve research on brain structure at death.