Fresh from nursing school and armed with a BSN, I began my professional career in 1971 as a nurse in the United States Navy. My first assignment at the US Naval Hospital in San Diego (Balboa) lasted only 9 months because several of us newer nurses were transferred to the tiny Pacific island of Guam (10 miles ? 30 miles, population 130,000) because of rising casualties from the war in Vietnam. I practiced nursing on Guam from 1972 through 1974. Even at that early stage in my career I knew I wanted to specialize in psychiatric nursing, noting that I went into the field to work with people and not "machines."
Thus, I was constantly annoyed when the nursing supervisor would pull me off the psychiatric units to work in the busy (and scary) intensive care unit, which was always full of terminally ill native Guamanians. (We cared for them because of the postWorld War II conventions governing the Trust Territories of Micronesia.) Little did I suspect at the time that the high prevalence of neurologic disorders I was treating (not very graciously) in the native population would become of interest to epidemiologists, clinicians, and researchers in Alzheimer's disease (AD) more than 20 years later.
Advances in AD
Recent discoveries related to the gene that codes for the amyloid precursor protein (APP) and genetic mutations on chromosomes 14, 19, and 21 have attracted widespread scientific and public interest. Stirring even more excitement are findings that were first reported in April 1993 related to APOE - Apolipoprotein E - which has three forms: apoE2, apoE3, and apoE4 (DHHS Advisory Panel on Alzheimer's Disease, 1993).
APOE is a normal cholesterol-carrying protein produced by a gene on chromosome 19, which appears to play a significant role in susceptibility to the development of AD. Researchers claim to have found a possible mechanism by which apoE3 protects against abnormal changes in proteins that lead to tangles associated with dementia. Interestingly, apoE4 appears to leave these proteins unprotected.
Causing an even greater public furor and promoting inquiries from desperate family members was the recent Food and Drug Administration approval of the first specific medication for the treatment of Alzheimer's disease - tacrine hydrochloride (Cognex) - which is now commercially available. This medication increases the amount of acetylcholine (a neurotransmitter affected in AD) in the brain. Tacrine also has been found to reduce some of the cognitive problems associated with AD in some (25% to 30%) patients. Other promising drugs that target cognitive deficits in AD are expected on the market in the near future.
So, what exactly does this all have to do with Guam? Well, although genetic and pharmacologic research appear to be the "hottest" areas of current investigation, environmental factors are still under etiologic consideration, as scientists in the USA and abroad continue to investigate the role of environmental factors in the onset of AD. Perhaps the most publicized research in this area has focused on studies of heavy metals, such as aluminum, magnesium, silicon, and zinc.
A New Look at Environmental Factors
One of the more interesting aspects of the environmental hypothesis, however, deals with the "remarkable epidemic of neurologic disease seen in Guam during the past 50 years" (Berg, 1993). As Dr. Leonard Berg, director of the St. Louis Alzheimer Disease Research Center, noted, the clinical picture of affected Guamanians varies from a dementia similar to that found in Alzheimer's disease to parkinsonism to a disease similar to amyotrophic lateral sclerosis - or what we Navy nurses used to call "Guamanian Lou Gehrig's disease."
Moreover, these diseases are not only more prevalent on Guam, but they also tend to occur approximately 15 to 20 years earlier in Guamanians than in residents of the United States. Persons in their 30s may be affected, and they often follow a much shorter clinical course on Guam than in this country. The common factor found in all three of these clinical manifestations is extensive formations of neurofibrillary tangles found in affected Guamanian brains. Increasing evidence suggests that the cause may be exposure of island natives to toxic chemical substances that destroy nerve cells, which may lead to AIzheimer's-like tangles.
The Unknown Link
With support from the National Institute on Aging, researchers like Dr. Leonard Kurland at the Mayo Clinic are currently studying Guamanians who have been brought to Rochester, Minnesota, in an effort to help explain the mystery of AD. Kurland noted that there are no indications that affected Guamanians have been exposed to excess aluminum, a popular hypothesis proposed in recent years (Van Beusekom, 1992).
Instead, he believes that the native cycad seed that comes from the sago palm tree may be the culprit in the unusually high number of neurologic diseases found in this area of the world. Guamanian natives extensively used this seed to make flour during the Japanese occupation of World War II. The time frame correlates with the long latency period associated with many neurologic diseases. Cycad contains a potent cancer-causing agent known as cycasin that possibly could have a cumulative toxic effect on the nervous system (Van Beusekom, 1992). As in most fields of investigation, it will undoubtedly be many years before we fully understand the role of environmental toxins in the onset of AD and other devastating neurologic disorders.
In the meantime, I realized that if I had only been more attentive and inquisitive (rather than hostile) during those shifts I spent working in the intensive care unit at the US Naval Hospital in Guam, I might be on the cutting edge of science today. I also cannot help wondering if any of the Guamanian food I consumed during my 2 years on the island was made from the seeds of the sago palm!
- Berg, L. (1993, February) Clinical Research Issues in Alzheimer's Disease. Paper presented at the Bryan Conference, Duke University, Durham, NC.
- DHHS Advisory Panel on Alzheimer's Disease. Interim Report. November, 1993.
- Van Beusekom, M. Answers in Guam? Visitors may help Mayo solve mystery of Alzheimer's. Rochester Post Bulletin, November 12, 1992.