World War II Vets Study Still Providing MH Data

Genetic, medical, and social factors combine to affect the risk of developing depression in later life. Thanks to the amazing tenacity of researchers and participants of the Honolulu-Asia Aging Study (HAAS), the neurobiological picture of aging is becoming clearer with every analysis.

At the American Association of Geriatric Psychiatry (AAGP) annual meeting in Honolulu in March, Kamal Masaki, M.D., a professor of geriatric medicine at the University of Hawaii at Manoa, and colleagues on the HAAS team discussed risk factors and comorbid diseases affecting the incidence of depressive symptoms in elderly Japanese-American men living in Hawaii. Their data provide some unexpected insights.

Participants in the study were originally assembled in 1964 as part of a long-term epidemiological study of heart disease funded by the National Heart, Lung and Blood Institute. The original study enrolled three groups of men with Japanese ancestry in Japan, Honolulu, and San Francisco. More than 8,000 men living in Oahu, Hawaii, who were listed in the World War II Selective Service Registration and were born between 1900 and 1919, were followed for more than four decades.

In 1991, the HAAS was established with funding from the National Institute on Aging based on the original Hawaii population of the heart study as they became older. The researchers collected a mountain of health and demographic data from exhaustive interviews, physical examinations, hospital records, genetic tests, and obituaries and medical examiners' records. Four extensive analyses were conducted from 1991 to 2000, and the surveillance is still ongoing.

The main objective of HAAS was to assess the prevalence, incidence, and risk factors of dementia, depressive symptoms, and other health-related changes with age. In the first examination of HAAS, 3,741 of the original cohort, then aged 71 to 93 participated. The most recent follow-up took place from 1999 to 2000 and had an impressive 1,523 participants.

Dementia, Genes Interconnect

Depressive symptoms often precede a diagnosis of Alzheimer's disease or other dementia. Carrying the APOE4 allele is a known risk factor for Alzheimer's, and some studies suggest it is associated with late-life depression. G. Webster Ross, M.D., associate chief of staff for research and development at the Veterans Affairs Pacific Islands Health Care System in Honolulu, presented analyses of HAAS data suggesting a combined effect of the apolipoprotein E4 (APOE4) gene and depressive symptoms on the risk for dementia.

Depressive symptoms were assessed using an 11-item version of the Center for Epidemiologic Studies Depression (CESD-11) scale with a score range from 0 to 33. A score of 9 or greater was considered to indicate depressive symptoms. Participants who were taking antidepressants were also considered to have depressive symptoms.

In 1,932 men in the HAAS cohort who had no dementia or cognitive impairment at baseline examination from 1991 to 1993, the risk of developing Alzheimer's in the following six years increased significantly at a risk ratio of 1.9 in men with baseline depressive symptoms compared with those who had neither depressive symptoms nor APOE4. However, for those who had both APOE4 and depressive symptoms, the incidence of Alzheimer's shot up to sevenfold. Having both risk factors was also associated with a 10.7-fold increase in the incidence of mixed dementia, but the risk ratio did not reach statistical significance for vascular dementia. The risk remained significant after controlling for age, education, and self-reported memory complaints. Interestingly, having only the APOE4 risk factor was not associated with a significantly increased risk of developing dementia in six years. The results of this study were published in the August 2008 Archives of General Psychiatry.

BP Drop Predicts Depression Risk

Orthostatic hypotension, a measure of autonomic nervous system dysfunction, was a predictor of developing depressive symptoms during the eight years of follow-up, according to the analyses conducted by Aaron McMurtray, M.D., an assistant professor of medicine and a neurologist at the University of Hawaii at Manoa, and fellow HAAS researchers.

In the study cohort, the prevalence of depressive symptoms was 10.6 percent at the baseline examination from 1991 to 1993. At the most recent follow-up examination during the period 1999 to 2000, 9.8 percent of the participants with no baseline depressive symptoms developed these symptoms during the eight-year period. Subjects were considered to have orthostatic hypotension if they experienced a drop in systolic blood pressure greater than or equal to 20 mm Hg from the supine to the standing position at 3 minutes or a drop in diastolic blood pressure greater than or equal to 10 mm Hg on standing, or both.

After controlling for age, education, marital status, and cardiovascular risk factors, the researchers found that participants who had orthostatic hypotension at baseline had a twofold increase in the incidence of depressive symptoms compared with those without orthostatic hypotension. However, the presence of this condition was not significantly associated with the baseline prevalence of depressive symptoms, suggesting that it is a predictor that preceded the mood symptoms.

Toby Smith, D.O., presented analyses on the relationship between physical activity levels and the incidence of depressive symptoms measured by CESD-11 at baseline and eight years later. Participants' physical activity was based on daily walking distance and categorized into low (less than a quarter mile), intermediate (a quarter to 1.5 miles), and high levels (more than 1.5 miles). After controlling for factors such as marital status, chronic diseases, and cognitive and functional impairment, the researchers found that the risk of developing depressive symptoms was significantly decreased with increasing levels of walking in the healthy elderly men, but the protective effect was not significant in those with coronary heart disease, stroke, cancer, Parkinson's disease, dementia, or cognitive impairment. “The healthy population [were the ones who] benefited the most from walking,” said Smith.

The HAAS was unusual for the long-term stability of the cohort, Masaki pointed out. The response rate was extremely high throughout the four decades, and very few participants moved off of Oahu. Most important, the participants were incredibly dedicated. “We have to acknowledge the loyalty of the men in this cohort for the last 44 years,” she said. “These are absolutely amazing men who had given a lot to [the study], all from altruism.”

Many participants belonged to the 442nd Regimental Combat Team of the U.S. Army in World War II, known as the most decorated unit in U.S. military history.

“These were Japanese Americans during World War II who had a lot to prove. Many of their relatives were interned in camps in California and other places on the continent,” Masaki said.

HAAS data continue to be generated to illuminate the complex biological and psychiatric process of aging.

An abstract of “Apolipoprotein E 4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men: The Honolulu Aging Study” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/65/8/906>.▪