VANCOUVER—The quality and quantity of sleep may be associated with the risk for cognitive decline, according to four studies presented at the 2012 Alzheimer’s Association International Conference. Treatments for insomnia or circadian rhythm delay might reduce or prevent cognitive decline, investigators reported.
Sleep Duration and Cognition
Compared with a sleep duration of seven hours per day, sleep durations of five or fewer hours per day and of nine or more hours per day were associated with worse average memory at older ages, according to Elizabeth Devore, ScD, Associate Epidemiologist at Brigham and Women’s Hospital in Boston. Short and long sleep durations at midlife and in later life were both associated with worse memory in later life.
Dr. Devore and her colleagues examined 15,263 women age 70 or older who had participated in the Nurses’ Health Study. The researchers performed one initial cognitive assessment and three biennial follow-up assessments of each participant. At baseline, the subjects reported sleep duration in midlife and in later life. The investigators used multivariable-adjusted mixed linear regression models to estimate mean differences in slopes of cognitive decline in several categories of sleep duration. Multivariable-adjusted linear regression was used to estimate mean differences in overall cognitive status at older age.
Women with sleep durations that changed two hours per day or more between midlife and later life had worse average memory at older ages, compared with those whose sleep duration did not change. “Regardless of where women started out in midlife, in terms of their sleep duration, the big changes seemed to be a problem for memory,” said Dr. Devore. “These findings indicate that extreme sleep durations or greater changes in sleep duration over time may contribute to cognitive decrements in older adults.”
Delayed Acrophase May Increase Risk of Dementia
People who experienced a shift in circadian rhythm acrophase had a risk of dementia nearly double that of people whose circadian rhythm remained stable, said Kristine Yaffe, MD, Professor of Psychiatry, Neurology, Epidemiology, and Biostatistics at the University of California, San Francisco. The finding was particularly true for patients whose shift was toward the later part of the day. Circadian rhythms that were not pronounced were also associated with an increased risk of dementia and mild cognitive impairment.
The results stem from Dr. Yaffe’s prospective study of 3,000 community-dwelling women. At enrollment, all participants were age 65 or older. At year 15, Dr. Yaffe and her colleagues assessed patients’ sleep parameters through actigraphy and polysomnography. Five years later, the researchers assessed patients’ cognitive outcomes through a battery of neuropsychologic tests. Patients’ clinical cognitive status was adjudicated.
Women with sleep-disordered breathing at baseline had nearly double the risk of developing dementia or mild cognitive impairment five years later, compared with women without sleep-disordered breathing. “It seems to be the hypoxia that’s related to risk of dementia and mild cognitive impairment, [not] the sleep fragmentation issue,” Dr. Yaffe commented.
This study may help explain why people with advanced dementia have alterations in their sleep–wake cycles, she added. “There may be some links between circadian shifts and amyloid-beta deposition in the brain. It may be possible that we could intervene and then delay, or somehow prevent, some of the cognitive sequelae.”
Excessive Daytime Sleepiness Linked to Cognitive Decline
Patients with excessive daytime sleepiness had a risk of global cognitive decline 30% higher than those without, according to Claudine Berr, MD, Research Director at INSERM in Montpellier, France. The increase was independent of many of the factors associated with cognitive decline or excessive daytime sleepiness.
The researchers observed no association, however, between cognitive decline and poor sleep quality, difficulty initiating sleep, or early morning awakening. People with difficulty maintaining sleep had a slightly reduced risk of cognitive decline.
As an ancillary project of the French Three-City Study of vascular diseases and dementia, Dr. Berr and colleagues administered sleep questionnaires to 4,894 healthy participants age 65 and older. All subjects had a Mini-Mental State Examination (MMSE) score of 24 or higher. Evaluations were conducted at participants’ homes or at the study center and repeated every two or three years. Patients were followed up for more than 10 years. Incident cognitive decline was defined as a four-point reduction in MMSE score during follow-up, and fluctuating scores were excluded.
The results confirm previous findings from the Honolulu–Asia Aging Study, noted Dr. Berr. Excessive daytime sleepiness is associated with depression, vascular diseases, metabolic syndrome, and diabetes. “It is important to treat sleep problems, particularly excessive daytime sleepiness, when we are able to recognize any cause. Prevention of diabetes and obesity is also important for excessive daytime sleepiness,” Dr. Berr concluded.
Amyloid Proteins Are Regulated in a Circadian Pattern
Amyloid-beta levels in CSF increased in a linear fashion over 36 hours, but the increase was smaller among patients with Alzheimer’s disease than among controls, according to Yafei Huang, PhD, postdoctoral research scholar at Washington University in St. Louis. Amyloid-beta levels did not increase in plasma.
Circadian fluctuations of amyloid-beta levels in plasma and CSF were twice as great among younger patients than among older patients. The degree of fluctuation did not differ greatly between older patients with Alzheimer’s disease and older patients without Alzheimer’s disease, however. The researchers found no correlation between amyloid-beta levels in CSF and those in plasma.
To understand the dynamics of CSF and plasma amyloid-beta levels during the course of the day, Dr. Huang studied three groups of participants. The first group included 80 patients with amyloid deposition and an average age of 72. The second group included age-matched controls, and the third group included healthy controls with an average age of 36. The investigators collected CSF and plasma samples from the participants every hour for 36 hours and measured the amyloid-beta levels in the samples.
“There is a very poor correlation between plasma and CSF amyloid-beta levels,” said Dr. Huang. “Plasma amyloid-beta levels are not good surrogate markers for CSF amyloid-beta levels,” she added. “When we use amyloid-beta levels as biomarkers, we have to keep this in mind. Time of sampling is very important, too.”
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Spira AP, Covinsky K, Rebok GW, et al. Poor sleep quality and functional decline in older women. J Am Geriatr Soc. 2012;60(6):1092-1098.