Sleep Duration, Sleep Disorders, and Circadian Patterns are Risk Factors and Indicators of Cognitive Decline

VANCOUVER, British Columbia, July 16, 2012 /PRNewswire-USNewswire/ -- Four studies reported today at the Alzheimer's Association International Conference® 2012 (AAIC® 2012) in Vancouver suggest a relationship between sleep quality and quantity and risk of cognitive decline, and that interventions to normalize sleep duration and correct sleep disorders may not only improve quality of life, but have potential to reduce or prevent cognitive decline.

"We know that sleep patterns change as people age and that poor sleep affects overall health. What we don't know for certain is whether poor sleep has long-term consequences on cognitive function," said William Thies, PhD, Alzheimer's Association® chief medical and scientific officer.

"The studies presented today at AAIC suggest that cognitive health declines over the long term in some people with sleep problems. The good news is that tools already exist to monitor sleep duration and quality and to intervene to help return sleep patterns to normal. If we do this, there is the possibility that we may also help people preserve their cognitive health, but that needs to be tested," Thies added.

Too little and too much sleep are associated with lower cognition

Growing evidence suggests that sleep duration that is shorter or longer than the recommended seven hours per day may increase risk of cardiovascular disease and type 2 diabetes. However, little research has been conducted examining whether sleep duration influences cognition among older individuals.

Elizabeth Devore, ScD, of Brigham and Women's Hospital, Boston, and colleagues examined data for more than 15,000 participants in the Nurses' Health Study. All were age 70 or older at their first cognitive examination between 1995 and 2000. Follow-up cognitive assessments were conducted every other year for six years. Participants' daily sleep duration was categorized as less than or equal to 5, 6, 7, 8 or greater than or equal to 9 hours (7 hours per day was considered normal). Average sleep duration was self-reported in 1986 (when women were ages 40 to 65) and 2000 (when women were ages 54 to 79). 

The scientists found that:

• Participants who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.
• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.
• Too little or too much sleep was cognitively equivalent to aging by 2 years.

When the researchers evaluated the effects of change in sleep duration from mid- to later- life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration. 

To explore sleep duration in relation to an early biomarker of Alzheimer's, the scientists examined the association with plasma levels of a ratio of proteins indicative of Alzheimer's disease brain changes (beta amyloid 42/40 ratio), which was measured in a small subset of women who provided blood samples in 1999-2000. They found that sleep durations of more than 7 or less than 7 hours per day were associated with declining ratios of amyloid-beta 42/40 compared to sleep durations of 7 hours per day.

"Our findings support the notion that extreme sleep durations and changes in sleep duration over time may contribute to cognitive decline and early Alzheimer's changes in older adults," Devore said. "The public health implications of these findings could be substantial, as they might lead to the eventual identification of sleep- and circadian- based strategies for reducing risk of cognitive impairment and Alzheimer's."

Sleep disorders, circadian disruptions associated with increased risk of cognitive impairment

As people age, they are more likely to develop problems with sleeping, such as insomnia, sleep apnea and disruptions in circadian rhythm. (Circadian rhythms are physical, mental and behavioral changes that follow a 24-hour cycle.) Whether these problems affect one's cognitive function or risk of developing mild cognitive impairment (MCI) or dementia is not definitively known.

"Studies that have explored the relationship between sleep and dementia are often cross sectional and depend on the participant's self-report rather than objective measures of sleep quality," said Kristine Yaffe, MD, of the University of California, San Francisco. 

Instead, Yaffe and colleagues conducted a series of studies evaluating more than 1,300 older women (greater than or equal to 75) enrolled in a large multi-center study to investigate the relationship between objectively measured sleep quality (using actigraphy* and polysomnography**) and adverse cognitive outcomes.

* Actigraphy is a method of monitoring rest/activity cycles. A small sensor unit is worn, usually on the wrist, to measure gross motor activity. The unit continually records the movements it undergoes.

** Polysomnography, also known as a sleep study, is a comprehensive recording of the physical changes that occur during sleep. The PSG monitors many body functions including brain, eye movements, muscle activity or skeletal muscle activation, breathing functions, and heart rhythm.

Over five years, the researchers assessed cognitive function and clinical cognitive status (normal, MCI or dementia) and obtained objective measures of sleep parameters, including sleep apnea, nighttime wakefulness, total sleep time, and shifts in circadian rhythm.

The scientists found that:

• Participants with sleep-disordered breathing or sleep apnea had more than twice the odds of developing MCI or dementia over the five years compared with those who did not have sleep-disordered breathing.
• Women who developed a disruption of their circadian rhythm (delay in the acrophase) over the five years were at increased risk of developing MCI or dementia compared with individuals who did not.
• Participants with greater nighttime wakefulness were more likely to score worse on tests of global cognition and verbal fluency than those without it.

"We believe that these results indicate that the relationship between sleep disordered breathing and dementia may be connected to the decrease in oxygen associated with sleep apnea and not to disrupted patterns of sleep," Yaffe said. 

"Overall, our findings support a relationship between sleep disturbances and cognitive decline in late age. They suggest that health practitioners should consider assessing older people with sleep disorders for changes in cognition," Yaffe said. "In addition, with additional long-term research, treatment of sleep disorders may be a promising method of delaying the development of MCI and dementia."

Sleep complaints and risk of cognitive decline in the elderly

Sleep quality and quantity often decrease as people age, but whether this is associated with risk of cognitive decline is a subject of ongoing investigation.

To better understand the potential relationship between sleep and cognitive decline, Dr. Claudine Berr of INSERM, Montpellier, France, and colleagues examined data from the French Three-City Study, an ongoing, long-term, multisite study of the relationship between vascular disease and dementia in community-dwelling individuals age 65 or older. Cognitive data were obtained at baseline and at 2, 4, and 8 years' follow-up; an ancillary project gathered data on sleep complaints at baseline.

Researchers analyzed data from 4,894 nondemented study participants who had completed sleep questionnaires, had Mini Mental State Examination (MMSE) scores of greater than or equal to 24 at baseline, and for whom data from at least one follow-up evaluation was available. Cognitive decline was defined as a decrease of four or more points on the MMSE at the three follow-up points. Researchers analyzed data for each of the five subcomponents of insomnia: (1) poor sleep quality, (2) difficulty initiating sleep, (3) difficulty maintaining sleep, and (4) early morning awakening; and excessive daytime sleepiness.

They found that excessive daytime sleepiness, which was reported by 17.9 percent of participants, independently increased risk of cognitive decline. In contrast, difficulty maintaining sleep, reported by 63.5 percent of participants, was negatively associated with risk of cognitive decline.

"These results suggest that excessive daytime sleepiness may be an early predictor of cognitive decline and that sleep complaints should be adequately evaluated in older persons," said the study's researchers.

Abnormal circadian patterns found in people with dementia

The amyloid hypothesis of Alzheimer's suggests that increased production or decreased clearance of amyloid-beta protein ultimately culminates in Alzheimer's disease. Changes in detectable amyloid proteins ion the body, such as decreased cerebrospinal fluid (CSF) amyloid-beta 42, have been recognized as biomarkers for the disease. However, the dynamics of amyloid-beta concentrations over time are not well understood.

The amyloid hypothesis of Alzheimer's suggests that increased production or decreased clearance of amyloid-beta 42 protein ultimately contributes to Alzheimer's disease. Changes in detectable amyloid proteins in the body, such as decreased cerebrospinal fluid (CSF) amyloid-beta 42, have been recognized as biomarkers for the disease. However, the dynamics of amyloid-beta concentrations over time, and changes in these proteins over the course of a 24-hour day, are not well understood. These dynamic changes are important to understand because CSF biological markers that could represent early Alzheimer's-like changes in people not yet showing Alzheimer's dementia symptoms will need to be measured consistently and accurately. The time of day of measurement and changes with age are critical to this standardized accurate measurement.

Supporting the above-mentioned initial data, a study at Washington University School of Medicine, St. Louis, Missouri, including people with dementia, age-matched participants, and younger participants, found circadian patterns in CSF and plasma amyloid beta, and CSF amyloid precursor protein, all of which are associated with Alzheimer's disease.

Yafei Huang MD, PhD and colleagues obtained hourly CSF and plasma samples over a 36-hour study period in all three groups. They investigated dynamic patterns of key Alzheimer's-associated amyloid-beta variants (amyloid-beta 40 and amyloid-beta 42) in CSF and plasma, and amyloid precursor protein (APP).  They then analyzed the effects of amyloidosis on circadian patterns, aging and correlations between CSF and plasma amyloid-beta.

Circadian patterns which were reflected in protein level changes over the course of a 36-hour period were observed in CSF and plasma amyloid-beta.  CSF APP also demonstrated a circadian pattern.  In addition, CSF APP-alpha, APP-beta, amyloid-beta 40, and amyloid-beta 42 were highly positively correlated in all participants without amyloidosis. However, in participants with amyloidosis, there is no correlation of amyloid-beta 42 to the other APP metabolites, suggesting that normal physiologic regulation of CSF amyloid-beta 42 is impaired in the presence of amyloidosis.

"Our study suggests amyloid proteins are dynamic and regulated in a circadian pattern that is part of the normal control of amyloid-beta concentrations. Regulatory mechanisms of these proteins may be altered with aging and amyloidosis," said Huang. "These findings support the idea of an active circadian regulation of beta-amyloid and may provide insight into the pathophysiological changes of Alzheimer's."

"These findings indicate that circadian rhythms and age should be studied further and better understood as research in CSF biological markers moves forward to ensure standardized, accurate measurements of key Alzheimer's proteins for future early detection of the disease," Thies added.

About AAIC

The Alzheimer's Association International Conference (AAIC) is the world's largest conference of its kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders.  As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association

The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. For more information, visit www.alz.org or call 800-272-3900.

SOURCE Alzheimer's Association