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.
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.
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>.▪