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. PHRI is part of a national collaborative network that examines possible factors contributing to neurodegenerative diseases.

The Honolulu Heart Program

The Honolulu Heart Program (HHP) was initially funded in 1965 through a contract from the NIH National Heart, Lung, and Blood Institute as a prospective study of environmental and biological causes of cardiovascular disease among Japanese American men living in Hawaii. The original study involved a cohort of 8,006 men born between 1900 and 1919. The HHP, in concert with a similar study conducted in European-ancestry Americans in Framingham, Massachusetts, has been seminal in generating a body of knowledge which, when translated into public health strategies, has resulted in nearly a 90% reduction in age-specific rates of fatal stroke, and similar dramatic fall in fatal myocardial infarction – in less than a half century. The ongoing research and examination of the HHP cohort has led to hundreds of studies, publications, and presentations, as well as considerable international recognition.

The HHP has been the basis of a long and successful research collaboration between PHRI and the Kuakini Medical Center, continuing to this day. It is the longest study of its kind with original participants, now ranging in age from 87 to 106, and the focus has shifted to healthcare issues of aging. A wealth of information has been gathered from throughout the lives of the study’s participants on diet, lifestyle, physical activity, and genetics, information that is crucial to understanding what helps people achieve a healthy old age.

The Honolulu Asia Aging Study

One of the projects utilizing the HHP cohort is the Honolulu Asia Aging Study (HAAS). PHRI Investigators have utilized the unique HHP population to study diseases associated with aging such as Alzheimer’s disease, vascular dementia, and Parkinson’s disease. One of the most extraordinary aspects of the HAAS project is research on brain structure at death, based largely on microscopic studies of different types of disease lesions in more than 30 brain regions, linking these to clinically recognized declines in function during the final years of life, and to a variety of exposures and personal characteristics decades earlier.

The HAAS project operates at the leading edge of research on Alzheimer’s disease, Parkinson’s disease, and the allied diseases that erode health, functioning, and personal identity in the final years of life. The autopsy represents the ultimate HHP/HAAS examination – the final contribution and definitive measure provided by our participants, generating maximum knowledge return on the investments of the men, their families, and the PHRI researchers. Through these contributions, and the intensive work of PHRI scientists, we are making real progress toward improving the longevity and health of our children, grandchildren, and future generations.

Neurotoxins and Neurodegenerative Disorders in Japanese-American Men Living in Hawaii

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 is an extension of the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS).

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 or Alzheimer changes 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 600 Japanese-American male descendents who were participants in the Honolulu Heart Program/Honolulu Asia Aging Study.

Parkinson’s Disease Neuroprotection Trial

Honolulu was selected to be one of the clinical centers for this multicenter, double-blind, placebo-controlled, clinical trial to determine whether two or more specific agents can provide neuroprotection in early Parkinson’s disease. Toxicity and tolerability of chosen agents will also be determined.