Alzheimer’s and Stress: A New Study Reaffirms the Link

It has been known for years that stress contributes to heart disease, insomnia, digestive disorders and a host of other health problems. Now there's increasing evidence that it also may trigger Alzheimer’s Disease.

A study released in March by the University of California, San Diego School of Medicine appears to back up earlier hypotheses that link stress with Alzheimer's. But not all types of stress are to blame.

Acute stress, caused by a sudden, single event such as an accident, is not implicated in the study, which was published in Proceedings of the National Academy of Sciences. It is chronic stress — the ongoing, unrelenting stress you might experience in, say, a difficult job or living situation — that's the culprit.

How the Test Was Done

Robert A. Rissman, PhD, assistant professor of neurosciences and lead author of the UC San Diego study, says it shows how chronic stress may lead to pathological changes in the brain.

In the study, mice were placed in vented plastic tubes for 30 minutes a day over a two-week period. While inside the tubes, they were denied access to food and water. Rissman notes that the effect of restraining the mice has been found in endocrinological studies to be “roughly equivalent to the … stress experienced by humans

” during prolonged periods of emotional strain.

"

This isn’t an exact science," he adds, "but the data look pretty convincing.”

 

Exposure to chronic stress induced insoluble protein clumps in the brains of the mice, similar to those seen in the brains of Alzheimer’s patients.

Previous studies have also shown a strong connection between stress and Alzheimer’s. In one conducted at the Max Planck Institute of Psychiatry in Munich, which was published in the Journal of Neuroscience in May 2011, persistent stress in rats led to a similar result: the formation of clumps in the brain and, ultimately, memory loss.

But what's significant about the UC San Diego study, Rissman says, is that earlier studies showing the connection between stress and the protein clumps usually involved mice with rare genetic mutations that promoted the pathology. “Here we haven’t used any mutations at all to get our phenotype … just exposure to emotional stress,’’ he says.

Alzheimer's Expected to Soar

Estimates of the number of Americans afflicted by Alzheimer’s range from 5.1 million to 5.4 million, and someone develops the disease every 68 seconds, according to the Alzheimer’s Association. Absent a cure, that figure is expected to climb as high as 16 million by 2050 as baby boomers age.

 

Mortality figures are hard to pin down, since patients may die as a result of complications from Alzheimer’s rather than the disease itself. Between 2000 and 2008, however, deaths attributed to Alzheimer’s increased 66 percent, while those linked to heart disease — the number one cause of death — declined 13 percent, according to the association.

 

The Alzheimer’s clumps, known as neurofibrillary tangles, or NFTs, are formed by a process called the hyperphosphorylation of naturally occurring tau proteins. NFTs have been found to kill nerve cells in the brain, particularly in the hippocampus area, which creates, organizes and stores our memories. That is the first region of the brain affected by tau pathology and the hardest hit by Alzheimer’s, sustaining substantial cell death and shrinkage, according to the research.

Chronic Stress: Too Much of a Good Thing?

Rissman acknowledges that a certain amount of stress is inevitable in life and may even be healthy.

 

"Acute stress" — the kind caused by a single event — "may be useful for brain plasticity," he says, referring to the phenomenon of change and learning in the adult brain. But chronic, ongoing stress may lead to pathological changes in stress circuitry. As Rissman puts it, "It may be too much of a good thing.” 

Especially as we age.

 

As we get older, the stress of daily life that we handled easily in our 20s and 30s is more likely to cause problems. The reason for this is simple: Just like everything else, our neuron circuits apparently wear out over time and are less able to rebound.

 

“Age is the primary known risk factor for Alzheimer’s Disease,” says Rissman. “It may be that as we age, our neurons just aren’t as [resilient] as they once were, and some succumb.”

The Effects of Job-Related Stress

Yet another study, conducted in Sweden and released earlier in March by Amsterdam-based Elsevier, shows a link between work-related stress and Alzheimer's. But this time the subjects were not rodents.

In this case, a group of researchers, many of them from Stockholm University, followed 913 people 75 and older over a six-year period to look at the long-term effect of job-related stress. Their finding: Continuous emotional stress experienced by those with low job control and high job strain was associated with an increased risk of dementia and Alzheimer's.

The Good New for Researchers

All of this is good news for researchers: The findings pave the way toward exciting new research possibilities aimed at preventing or delaying the disease. But making such strides will take time, Rissman says. “I would hope that we could get the necessary [research] done within the next five years.’’

 

In the meantime, stress remains a fact of life. “You can’t eliminate stress,” Rissman says. “We all need to be able to respond at some level to stressful stimuli.’’

There may be benefits in changing jobs, seeking counseling, exercising, meditating or taking other measures to alleviate chronic stress. But Rissman has another long-term goal: to develop a way to reduce the effects of stress on neurons, so it doesn’t result in permanent damage.