Campus & Community

Getting into rhythms of Alzheimer’s disease

6 min read
David Harper holds instruments to measure body temperature (left) and physical activity (right) of patients in a psychiatric hospital. Daily rhythmic changes in the readings reveal whether a person has Alzheimer’s disease or some other type of dementia. (Staff photo by Jon Chase)

By clocking the biorhythms of older people, researchers have come up with a way to tell if a person has Alzheimer’s disease. As new drugs and even a vaccine are developed for this personality-robbing disease, it becomes critically important to make sure these treatments are given to the right people.

Victims of Alzheimer’s lose their memories and suffer distressful personality changes. But the same things happen in other types of progressive dementia. At this point, doctors can’t tell for sure if someone has Alzheimer’s until he or she dies. When patients are autopsied, if they’ve had Alzheimer’s, their brains reveal clumps of sticky, memory-dulling plaques.

Therefore, you can imagine the surprise of researchers when they autopsied 38 people thought to have Alzheimer’s and found no plaques in the brains of 11 of them.

“That was an ‘Ah ha!’ moment for us.” says David Harper, a research psychologist at McLean Hospital, an affiliate of the Harvard Medical School located in Belmont, Mass. “We went back and looked at differences in the daily rhythms that we’d previously measured. Sure enough, Alzheimer’s can be distinguished from the other major form of progressive dementia, frontotemporal degeneration, by the daily waxing and waning of body temperature and uncontrolled physical activity.”

For example, patients with advanced Alzheimer’s seldom get a good night’s sleep or enjoy restful naps. Those with frontotemporal dementia, however, can reach a daily quiet state, although not necessary at night when they try to sleep.

A natural clock deep in the brain of humans and other species controls daily biological rhythms, including body temperatures. Nondemented people and those with degeneration of the front part of the brain behind the temples hit their lowest temperature between 4 and 5 a.m. In Alzheimer’s patients, temperature and activity lows are delayed past 9 a.m., sometimes to as late as 12:30 p.m.

“This surprising delay apparently is a distinctive hallmark of Alzheimer’s disease, one that should help us to diagnose the problem without a brain autopsy,” Harper notes. That, in turn, would avoid giving drugs meant for Alzheimer’s patients to those who have frontotemporal dementia, a group which Harper estimates could be 10-20 percent of those now diagnosed with Alzheimer’s.

Trying to get more sleep

The rhythm findings could also lead to better ways to treat sleep disturbances that bedevil all people with progressive dementia. Inability to care for someone who cannot rest easily is a prime reason for the institutionalization of patients. Frontotemporal degeneration patients show a different pattern of body temperature and activity disturbances, but they, too, suffer sleeping problems.

“In dementias, you have memory and behavioral disturbances that are horrific, but you also have sleep problems, hallucinations, and delusions,” Harper points out. “Sleep problems are actually more disturbing to caregivers than memory and cognitive symptoms, and so are often cited as the primary factor behind the decision to institutionalize.”

But patients can go from bad to worse in unfamiliar surroundings. In fact, one explanation for disturbances in daily rhythms blames the institutions. The brain’s timekeeper needs the 24-hour cycle of light and dark to set itself properly. But dementia patients may remain inside most of the time where artificial lighting is much the same day or night.

Harper and his colleagues from Harvard Medical School, Brown University in Providence, R.I., and Boston University School of Medicine agree that institutionalization may contribute to daily rhythm problems. However, it appears that internal changes in the brain’s timekeeper are the main cause.

When the brain clocks of shift workers, international travelers, astronauts, and others go awry, they can be reset by exposure to bright light. Shift workers, for instance, can sit in front of light boxes at various times and intervals to adjust their bodies to sleeping when it’s light outside and staying alert when it’s dark.

“Light behaves like a drug that can readjust daily body rhythms,” says Harper.

But changing light exposure hasn’t worked consistently for restless Alzheimer’s patients. One reason, of course, is that some of these people actually have frontotemporal dementia. Light probably won’t aid these people because their temperature rhythms are the same as those of normal people, even though their activity cycles can be chaotic.

Alzheimer patients often fall asleep and wake up at unusual hours. To get them into a better cycle, clinicians have tried exposing them to extra light around 9 a.m., after their body temperatures reach their lowest point.

However, in some patients, the time of lowest temperature may be delayed several hours beyond 9 a.m.

In these cases, light therapy can make things worse. Thus, Harper concludes, “taking a one-size-fits-all approach to adjusting the daily rhythm may be counterproductive. When giving light treatment, you need to make sure the patient has Alzheimer’s, then measure the actual daily rhythm before you start.”

New treatments

Researchers have also tried to reset biological clocks with the help of the hormone melatonin. Darkness stimulates the brain to secrete this hormone as a natural sleeping pill. (Morning light suppresses melatonin.) Thus, the hormone might be given to reset the body’s timekeeper to a more normal and restful cycle.

So far, things haven’t worked out that way. Some people claim evidence that melatonin shifts daily rhythms, or that it’s a marvelous sleep inducer. Others say it works only marginally, if at all. Harper calls it “a fascinating hormone that’s going to keep researchers busy for a while.”

Meanwhile, Harper and his team continue to study more patients with Alzheimer’s and frontotemporal dementia. What they have already learned makes these studies more productive.

“The best thing we can do for patients now is to increase our understanding of the pathways involved in translating the ticking of the brain’s internal clock into changes in activity and rest rhythms,” Harper believes. For example, he wants to measure how brain activity translates into the personality disturbances seen in patients with the different types of dementia.

To date, all people in this study have been males with severe dementia. Females exhibit different changes in daily rhythms as they age. Harper would like to find ways to distinguish which differences are natural and which are due to dementia.

Then there’s the question about mild stages of Alzheimer’s. Would daily rhythm changes be detectable at all, or would treatments such as light boxes be more effective? If dissonant rhythms can be used to diagnose Alzheimer’s before obvious abnormalities in memory and behavior show up, then the few drugs available might yield better results.