Autopsies shine light on dementia


POSTED: Sunday, October 04, 2009

Even in death, many of the 8,006 Japanese-American men who participated in a decades-long health study in Honolulu continue to contribute to the understanding of Alzheimer's and other diseases.

Investigators led by Dr. Lon White of the Pacific Health Research Institute have done about 800 autopsies on the men, recruited in 1965 for a study of heart disease and stroke, at Kuakini Medical Center with family permission.

The Honolulu-Asia Aging Study was expanded over the years with research and significant discoveries on diseases associated with aging. The program has received more than $72 million in federal funds since the 1960s.

Only about 400 of the original 8,006 men are still living. Kuakini is receiving $1.1 million in federal funds to continue the research.

The men in the study group were born from 1900 to 1919 and identified through World War II Selective Service registration files. The youngest now living is 90, White said.

Pacific Health Research Institute doctors and associates have followed the men, assessing their cognitive, motor and sensory functions; lifestyle; health; and illnesses. Now, as they do autopsies, White said, “;we are in a unique position to understand the causes and meanings of those changes we see in the brain.”;

With the volunteers who “;signed onto a lifetime study”; 44 years ago, White said the team is striving for basic understanding to prevent or slow the progression of dementia and “;turn around those we could turn around.”;

Fewer than six studies worldwide are looking intensely at dementia and Alzheimer's disease. The Honolulu study has been a leader with some findings “;revolutionizing the way people think about these diseases,”; White said.

“;We have been able to correct a huge number of important misunderstandings related to the causes of dementia,”; he said, adding that “;loss of cognition late in life is a whole lot more complicated than we used to think it was.”;

He said the researchers found processes contributing to dementia that have been attributed incorrectly to Alzheimer's disease.

For example, they have found changes in tiny arteries of the brain produced by a vascular disease, molecular changes often seen in Parkinson's disease in the cerebral cortex, which has a role in memory, and loss of neurons in the area of the brain associated with memory.

While the researchers are interested in the causes of death, White said, “;We're more interested in the value of what we can learn from these for the rest of the world and future of people.”;

He said they are looking for patterns linked to changes in the brain — “;why some people have changes to a large extent and others very few. It's really detective work.”;

The study eventually will provide information on nearly 1,000 men with any signs of dementia measured during their lives, such as trouble walking, talking or interacting socially, White said. “;This gives us a chance to follow it right into the structures, cells and molecules in the brain to find out what is going on. It is an incredible opportunity.”;

He said autopsies of the brain have rarely been done in the past 20 years except when people die in peculiar situations, and ways of applying modern science to understand what is happening in the brain are limited.

“;There is just no good information about how these diseases progress and what's going on to cause them.”;

Yet the risk of suffering dementia or Alzheimer's disease doubles every five years, he said. With people living longer, “;it means half of them will spend the last years of our lives with individual identities lost or eroded away by terrible diseases.”;