April 17, 2000 (Berkeley, Calif.) -- For years, Maria Cusenza's three children didn't worry much about her. Through her 60s and early 70s, Cusenza was a busy woman living in her own apartment in San Francisco. But in recent years the situation has changed. Cusenza, now 80, has marked memory loss. By afternoon, she forgets a conversation she had that morning. During the week she forgets a weekend outing.
"We have to check on her more often, to make sure she is healthy and safe," says Dorothy Cusenza, 57, one of Maria's two daughters. For the first time Cusenza and her family are talking about home helpers, retirement homes, or having Mom move in with one of her kids. As her forgetfulness increases, she sinks farther and farther into depression.
Doctors are still trying to determine why Cusenza's memory is fading; they say there's little they can do. But her family wonders if her depression might be causing her memory problems rather than the other way around.
They are intrigued by new research showing that stress and depression may cause some forms of memory loss. The research is important because it suggests that not all memory loss is an inevitable part of aging. '"If you look at a patient as having irreversible dementia, you won't do anything," says Sonia Lupien, PhD, a neuroscientist at Douglas Hospital in Montreal. "If you treat the depression, you can stop the increase of cortisol and prevent the memory loss."
Studies show that prolonged depression or stress leads to elevated levels of cortisol, a "stress" hormone produced by the adrenal glands. This in turn appears to shrink or atrophy the hippocampus, the sea-horse shaped part of the brain associated with many kinds of memory and learning.
"The hippocampus is an organ of the brain that is particularly vulnerable to stress and stress hormones," says Bruce McEwen, the head of neuroendocrinology at Rockefeller University in New York.
While cortisol levels normally fluctuate over the course of a day and night, they often soar when a person is faced with a stressful situation, such as a job interview or a school test. Studies have shown that this affects memory. For example, researchers reported in the April 2000 issue of Nature Neuroscience that people taking cortisone pills (which metabolizes to cortisol in the body) were not as good at remembering a list of words as people taking placebo pills.
For many people, depression appears to cause similar damage; their cortisol levels remain slightly elevated as long as they are depressed. This moderate but constant drip-drip of the cortisol faucet appears to wear down the hippocampus.
In a review of several long-term studies published in the October 1999 issue of Reviews in the Neurosciences, Lupien concluded that this process is particularly damaging in the elderly.
But there's no strong evidence that the hippocampus shrinks as a part of normal aging. In one recent study, Yvette Sheline, MD, a professor of psychiatry at Washington University in St. Louis, used magnetic resonance imaging to measure the hippocampus of 48 women aged 23 to 86, half of whom had a history of clinical depression, half of whom did not.
The women with depression had smaller hippocampuses and scored lower on memory tests than the non-depressed group, regardless of age.
"We expected to see an effect from aging. Instead we saw significant volume loss only in patients with a history of depression," says Sheline, whose study was published in the June 14, 1999 issue of the Journal of Neuroscience.
"Research shows that when depression is treated, cognitive function, including memory, improves. The earlier we can recognize the symptoms, the more likely we are to arrest or slow down the degeneration of the brain," McEwen says.
Still, more studies are needed to fully understand the connection between emotions and memory, cautions Mony de Leon, a psychiatrist and professor at New York University's medical school. The cortisol-hippocampus research is an exciting start, he says, but much remains a mystery.
For example, researchers haven't yet determined what, if any, role cortisol plays in Alzheimer's disease. Studies show all people with Alzheimer's have hippocampal damage, but their cortisol production varies. "All of these things remain somewhat foggy," says de Leon. "It requires much more extensive investigation."
As for Cusenza, no one has any plans to measure her hippocampus. Such tests are rarely done, and they would tell doctors little because it wasn't measured before the onset of her symptoms. Still, her family is hopeful that treating her depression will put a halt to her slide into forgetfulness -- and dependence.
Kate Rauch has written about medicine for The Washington Post, Newsday, and many other publications. She lives in Albany, Calif.