Media Releases

U of T research helps explain why elderly are prone to sleep problems

August 20, 2014

TORONTO, ON — New research led by Uni­ver­si­ty of Toron­to neu­rol­o­gist Andrew Lim sheds light on sleep dis­rup­tion in aging adults.

“In many old­er peo­ple with insom­nia and oth­er pat­terns of sleep dis­rup­tion, the under­ly­ing cause is unknown,” said Lim, assis­tant pro­fes­sor of neu­rol­o­gy and neu­ro­sci­en­tist at Sun­ny­brook Health Sci­ences.

“We pro­vide evi­dence that loss of neu­rons in a par­tic­u­lar region of the brain that con­trols sleep may be an impor­tant con­trib­u­tor to insom­nia in many old­er indi­vid­u­als.”

Report­ed online August 20 in the jour­nal Brain, the new find­ings demon­strate for the first time that a group of inhibito­ry neu­rons, whose loss leads to sleep dis­rup­tion in exper­i­men­tal ani­mals, is sub­stan­tial­ly dimin­ished among the elder­ly and indi­vid­u­als with Alzheimer’s dis­ease. (See the jour­nal arti­cle.)

“These find­ings may one day lead to nov­el treat­ments for insom­nia and oth­er pat­terns of sleep dis­rup­tion in old age, there­by improv­ing qual­i­ty of life,” said Lim. “And giv­en recent evi­dence that sleep dis­rup­tion may pre­dis­pose to or poten­ti­ate the devel­op­ment of Alzheimer’s dis­ease, per­haps even pre­vent or slow the pro­gres­sion of Alzheimer’s dis­ease.”

On aver­age, peo­ple in their sev­en­ties have about one hour less sleep per night than those in their twen­ties, said co-author Clif­ford B. Saper, MD, PhD, chair­man of neu­rol­o­gy at Beth Israel Dea­coness Cen­tre and James Jack­son Put­nam Pro­fes­sor of Neu­rol­o­gy at Har­vard Med­ical School.

“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,” Saper said. “It now appears that loss of these neu­rons may be con­tribut­ing to these var­i­ous dis­or­ders as peo­ple age.”

In 1996, the Saper lab first dis­cov­ered that a key cell 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 is locat­ed in a sim­i­lar loca­tion and has the same inhibito­ry neu­ro­trans­mit­ter as the rats. The authors hypoth­e­sized that if the humans’ inter­me­di­ate nucle­us was impor­tant for human sleep and was homol­o­gous to the animal’s ven­tro­lat­er­al pre­op­tic nucle­us, then it may also sim­i­lar­ly reg­u­late humans’ sleep-wake cycles.

In order to test this hypoth­e­sis, the inves­ti­ga­tors ana­lyzed data from the Rush Mem­o­ry and Aging Project, a com­mu­ni­ty-based study of aging and demen­tia. The project began in 1997 and has been fol­low­ing a group of almost 1,000 sub­jects who entered the study as healthy 65-year-olds and are fol­lowed until their deaths, at which 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 their wear­ing a small wrist­watch-type device on their non-dom­i­nant arm for sev­en to 10 days,” said Lim, a for­mer mem­ber of the Saper lab. The actig­ra­phy device, which is water­proof, is worn 24 hours a day and there­by mon­i­tors all move­ments, large and small, divid­ed into 15-sec­ond inter­vals.

“Our pre­vi­ous work had deter­mined that acti­graph­ic read­ings indi­cat­ing absence of move­ment for five min­utes or longer cor­re­lat­ed with sleep inter­vals,” Lim said.

The authors exam­ined the brains of 45 study sub­jects (with a medi­an age at death of 89.2), iden­ti­fy­ing ven­tro­lat­er­al pre­op­tic neu­rons by stain­ing the brains for the neu­ro­trans­mit­ter galanin. They then cor­re­lat­ed the acti­graph­ic rest-activ­i­ty behav­iour of the 45 indi­vid­u­als in the year pri­or to 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 sub­jects with the largest num­ber of neu­rons (greater than 6,000) spent 50 per cent or more of the sleep time in pro­longed peri­ods of non-move­ment, while sub­jects with the fewest ven­tro­lat­er­al pre­op­tic neu­rons (few­er than 3,000) spent less than 40 per cent of their nights in extend­ed peri­ods of sleep. The results 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.


For more infor­ma­tion, con­tact:

Michael Kennedy
Media Rela­tions
Tel: 416–946-5025