As people grow older, they often have difficulty falling asleep and staying asleep. On top of that, they tend to awaken too early in the morning.
A new study from researchers at Beth Israel Deaconess Medical Center (BIDMC) in Boston and the University of Toronto/Sunnybrook Health Sciences Center helps explain why sleep becomes more fragmented with age.
The study’s findings show that a group of inhibitory neurons are substantially diminished among the elderly and individuals with Alzheimer’s disease, which leads to sleep disruption.
“On average, a person in his 70s has about one hour less sleep per night than a person in his 20s,” said senior author Clifford B. Saper, M.D., Ph.D., chairman of neurology at BIDMC.
“Sleep loss and sleep fragmentation is associated with a number of health issues, including cognitive dysfunction, increased blood pressure and vascular disease, and a tendency to develop type 2 diabetes. It now appears that loss of these neurons may be contributing to these various disorders as people age.”
Back in 1996, Saper’s lab discovered that the ventrolateral preoptic nucleus, a group of inhibitory neurons, was functioning as a “sleep switch” in rats, turning off the brain’s arousal systems to enable animals to fall asleep.
“Our experiments in animals showed that loss of these neurons produced profound insomnia, with animals sleeping only about 50 percent as much as normal and their remaining sleep being fragmented and disrupted,” he said.
A group of cells in the human brain, the intermediate nucleus, is located in a similar location and has the same inhibitory neurotransmitter, galanin, as the vetrolateral preoptic nucleus in rats, he said. That led Saper and his colleagues to hypothesize that if the intermediate nucleus was similar to the animal’s ventrolateral preoptic nucleus, then it may also regulate sleep-wake cycles.
To test their hypothesis, the researchers analyzed data from the Rush Memory and Aging Project, a community-based study of aging and dementia that began in 1997.
Almost 1,000 men and women entered the study as healthy 65-year-olds and are followed until their deaths. At that point, their brains are donated for research.
“Since 2005, most of the subjects in the Memory and Aging Project have been undergoing actigraphic recording every two years. This consists of wearing a small wristwatch-type device on their non-dominant arm for seven to 10 days,” said first author Andrew S. P. Lim, M.D., of the University of Toronto and Sunnybrook Health Sciences Center and formerly a member of the Saper lab.
The actigraphy device, which is waterproof, is worn 24 hours a day, monitoring all movements, large and small, divided into 15-second intervals.
“Our previous work had determined that these actigraphic recordings are a good measure of the amount and quality of sleep,” Lim said.
The researchers also examined the brains of 45 study subjects with a median age at death of 89.2. They identified the ventrolateral preoptic neurons by staining the brains for the neurotransmitter galanin. They then correlated the actigraphic rest-activity behavior of the 45 individuals in the year before their deaths with the number of remaining ventrolateral preoptic neurons at autopsy.
“We found that in the older patients who did not have Alzheimer’s disease, the number of ventrolateral preoptic neurons correlated inversely with the amount of sleep fragmentation,” said Saper. “The fewer the neurons, the more fragmented the sleep became.”
The people with the largest amount of neurons — greater than 6,000 — spent 50 percent or more of total rest time in prolonged periods of non-movement, which most likely represented sleep, according to the researchers. But the subjects with the fewest ventrolateral preoptic neurons — less than 3,000 — spent less than 40 percent of total rest time in extended periods of rest.
The findings further showed that among Alzheimer’s patients, most sleep impairment seemed to be related to the number of ventrolateral preoptic neurons that had been lost, the researchers reported.
“These findings provide the first evidence that the ventrolateral preoptic nucleus in humans probably plays a key role in causing sleep, and functions in a similar way to other species that have been studied,” said Saper.
“The loss of these neurons with aging and with Alzheimer’s disease may be an important reason why older individuals often face sleep disruptions. These results may, therefore, lead to new methods to diminish sleep problems in the elderly and prevent sleep-deprivation-related cognitive decline in people with dementia.”
The study was published in the journal Brain.