Bad Sleep Tied to Cognitive Decline

Three different studies all support the concept that sleep disturbances are associated with cognitive decline among older individuals.

Common sleep problems may be a sign of impending cognitive decline or even Alzheimer’s disease, according to results of several studies reported here.

Sleeping too little or too much, abnormal breathing during sleep, and excessive daytime sleepiness all were significantly associated with cognitive impairment — years later in some cases.

The studies were presented at a “featured research session” during the Alzheimer’s Association International Conference and at a press briefing beforehand.

Constantine Lyketsos, MD, of Johns Hopkins University, who moderated the press briefing, said the parallel results from three studies using different methodologies made them especially persuasive.

“It’s unusual that we have [multiple] studies coming together at the same time to say the same thing,” he said, “which is that sleep disruptions of various kinds throughout the lifespan are probably accelerators of cognitive aging and risk factors for dementia.”

The studies examined multiple aspects of disordered sleep:

  • Analysis of data from the Nurses’ Health Study comparing neurocognitive outcomes in participants according to their reported average sleep duration
  • Prospective study using actigraphy and polysomnography to evaluate sleep patterns and breathing, correlated with results of cognitive testing
  • Long-term observational study with participant-reported data on sleep disturbances and cognitive test results

Each of the studies found that abnormal sleep patterns went hand in hand with cognitive impairment.

Nurses’ Health Study

With more than 15,000 female participants followed for many years as they aged, the Nurses’ Health Study is an ideal platform for studying risk factors for cognitive decline, explained Elizabeth DeVore, ScD, of Brigham and Women’s Hospital in Boston.

The cognitive assessments using a battery of six separate tests were first performed when participants were at least 70 years old, and were repeated every 2 years over a 6-year period, DeVore said. Participants were questioned about average daily sleep duration near the time of the first cognitive evaluation.

Relative to participants reporting an average of 7 hours of daily sleep, mean scores on the four cognitive assessments were significantly lower for women who reported daily sleep of 5 hours or less, and also for those reporting 9 hours or more.

The mean cognitive deficit in the short-sleepers was 0.07 standardized units. In the excessive sleepers, it was 0.10 units.

DeVore said these deficits corresponded roughly to the cognitive decline normally occurring in 2 years in this age group.

Sleep-Disordered Breathing and Cognition

Led by Kristine Yaffe, MD, of the University of California San Francisco, this analysis involved participants in the Study of Osteoporotic Fractures, in which older women were followed for up to 20 years. A subgroup of the larger study also underwent detailed sleep monitoring using wrist actigraphy and polysomnography to evaluate sleep duration and latency, awakenings, and breathing parameters.

A total of 1,430 study participants underwent these analyses as well as assessments of cognitive function, producing diagnoses of mild cognitive impairment or dementia as appropriate.

An earlier look at these data were published last year in the Journal of the American Medical Association, based on fewer participants than Yaffe reported on here, although the general thrust was unchanged.

As in the JAMA report, Yaffe said that participants with sleep-disordered breathing, increased oxygen desaturation, or high percentages of time in apnea or hypopnea were at approximately doubled risk of a diagnosis of cognitive impairment or dementia.

Odds ratios for cognitive impairment or dementia with these measures of breathing abnormalities during sleep were 1.85, 1.71, and 2.04, respectively, after adjustments for age, race, body mass index, smoking, diabetes, hypertension, and medication use.

In addition, participants in the highest quartile of waking after sleep onset and those in the lowest quartile of sleep efficiency (the ratio of sleep to wake time) were at about triple the risk for entering a nursing home compared with the lowest/highest quartiles.

Three-City French Study

Also finding a strong relationship between abnormal sleep and cognitive decline was a third study reported by Claudine Berr, MD, PhD, of the French national INSERM laboratory in Montpellier. Called the Three-City Study, it followed about 4,900 people who were 65 or older at baseline in the cities of Bordeaux, Lyon, and Montpellier for 10 years with periodic physical and cognitive exams, as well as lifestyle interviews.

The study’s primary aim was to examine vascular risk factors in brain aging. But since the baseline interviews included questions about sleep problems, the data could be mined for relationships between sleep and cognitive function.

Among the questions were whether participants had trouble falling asleep and staying asleep, and whether they felt excessively sleepy during the day. They also were asked to rate their overall sleep quality and to count the number of recent insomnia episodes.

Cognitive outcomes were assessed in terms of declines in scores on the Mini-Mental State Examination, reflecting increased cognitive impairment.

In contrast to the findings reported by DeVore — and perhaps because of methodological differences between the two studies — Berr said that participants reporting some types of sleep problems actually were not at increased risk of cognitive decline. These included self-reported poor sleep quality, problems with falling asleep, and early morning awakenings.

In fact, participants reporting difficulty with staying asleep and those with frequent insomnia actually were less likely to experience cognitive decline during follow-up, with adjusted odds ratios of about 0.8.

But those who said they were frequently sleepy during the day were more likely to show cognitive decline, Berr said.

Does Poor Sleep Cause Cognitive Decline?

At the press briefing, all three researchers said they believed that sleep problems contribute in a causal way to cognitive decline, although they acknowledged that their studies could not prove such a relationship.

Yaffe said there may be a “bidirectional relationship” between cognitive and sleep problems, as there is between depression and cognitive impairment, although the latter is more clear-cut in terms of brain areas affected.

DeVore argued that the time lag seen in some of her data between sleep complaints and the subsequent onset of cognitive impairments suggests a causal link.

Lyketsos, the press briefing moderator, pointed out that there is an obvious mechanism by which sleep problems may cause cognitive impairment: namely, the hypoxia associated with sleep apnea.

“I think both the midlife finding [in the Nurses’ Health Study] and the hypoxia finding take us away from amyloid [as the sole mechanism underlying dementia] and strengthen the argument,” he said.

“All three studies basically say the same thing, so that’s why for me this is fairly persuasive that there’s something about sleep going wrong that’s predictive of cognitive change.”

By John Gever