As people age, they often report having problems sleeping, whether it be difficulty staying asleep or falling asleep in the first place. Researchers from Beth Israel Deaconess Medical Center (BIDMC) in Boston along with the University of Toronto have discovered why sleep worsens with age, and published their findings in the journal Brain.

Researchers looked inside the brain for answers and found a group of neurons significantly diminish overtime in the elderly and individuals diagnosed with Alzheimer’s disease, which is a type of dementia that disrupts a person’s memory, thinking, and behavior. They followed nearly 1,000 men and women who were 65 years of age until their deaths, and then examined their brains, which were donated to research.

“On average, a person in his 70s has about one hour less sleep per night than a person in his 20s,” said the study’s senior author Clifford B. Saper, chairman of neurology at BIDMC, in a press release. “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.”

Almost 20 years ago, Saper’s lab made an important discovery, finding that the ventrolateral preoptic nucleus was actually a “sleep switch” in rats. By turning it on and off, the researchers could control the brain’s arousal system, and it gave them the ability to make animals fall asleep. A group of cells in the human brain is in a similar location to the ventrolateral preoptic nucleus, and uses the same line of communication, known as the galanin neurotransmitter. This led Saper’s researchers to believe that both systems could regulate sleep-wake cycles, and a year later, they decided they needed to test their hypothesis with aging and Alzheimer’s patients. 

“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,” Saper said. “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. The fewer the neurons, the more fragmented the sleep became.”

Researchers relied on an actigraphy device, which is a waterproof wrist band that monitors all movements in 15-second intervals throughout the 24 hours in the day, in order to track sleep cycles. After looking at 45 study subjects’ brains with an average age of death at 90, they were able to identify the ventrolateral preoptic neurons by staining the brains to find the galanin neurotransmitter. They compared the brain to the rest-activity behavior the actigraphy device recorded the year before they died, and found that less activity in galanin was associated with worse sleep.

“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 the study’s co-author Andrew S. P. Lim, of the University of Toronto and Sunnybrook Health Sciences Center, in a press release. “Our previous work had determined that these actigraphic recordings are a good measure of the amount and quality of sleep.”

Those with the largest amount of neurons, which was considered greater than 6,000, spent 50 percent or more of their sleep with prolonged periods of non-movement. This reflected healthy sleep habits, however, the subjects that had fewest ventrolateral preoptc neurons, which was considered less than 3,000, spent less than 40 percent of their sleep in a prolonged healthy state of rest. This led researchers to conclude that this group of neurons are responsible for older people’s tossing and turning at night.

“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.”  

Source: Saper CB, Lim ASP, Ellison BA, et al. Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer’s disease. Brain. 2014.