Numerous studies indicate there is a strong relationship between sleep quality and neurocognitive functioning in adults. Sleep slow waves, an electrophysiological characteristic of non-REM sleep, are considered a reliable marker for sleep homeostasis and have been linked to the beneficial effects of sleep on neurocognitive performance. Yet sleep slow waves and overall sleep architecture have received little attention in older adults and have not been examined in older adults in amnestic mild cognitive impairment (aMCI). We will focus our investigation on amnestic MCI as these individuals have a greater risk for progression to Alzheimer's disease - approximately 40% go on to develop Alzheimer's disease within 4 years (Gauthier et al., 2006;Saykin &Wishart, 2003). Electrophysiologic measurements during sleep (such as polysomnography and high-density EEG) provide a unique modality for investigating brain function as they minimize many factors that may interfere with assessing cognitive function during wakefulness, (e.g., a subject's intelligence, attention, and/or motivation). In this investigation, we will use polysomnography to examine the macrostructure of sleep architecture and night time high-density EEG (hd-EEG) to examine the microstructure of sleep slow waves. We intend to harness the state-of-the-art expertise of the Wisconsin Sleep Center researchers (leaders in sleep physiology) and the VA expertise in dementia research to study sleep slow waves as a predictor of cognitive outcomes in aMCI. We predict that characteristics of sleep slow waves will be associated with symptom severity in aMCI and will be useful as a predictor of subsequent cognitive decline in aMCI.
Aims :
The aims of this investigation are: (1) To determine whether older Veterans with aMCI will demonstrate significant changes in their sleep architecture (via polysomnography) as compare to non-impaired Veterans at baseline and over time. (2) To determine whether older Veterans with aMCI will demonstrate significant changes in the synaptic strength and quality of sleep slow waves as compared to non-impaired Veterans with aMCI at baseline and over time. 2A.To determine if sleep slow wave synaptic strength (as measured by slow wave amplitude and slope via hd-EEG) is reduced in older Veterans with aMCI and non- impaired controls at baseline and over time. 2B. To determine if the source of the sleep slow waves and the speed of the traveling waves (as measured by hd-EEG) are reduced in areas of the brain known to be affected by aMCI, in Veterans with aMCI as compared to non-impaired controls at baseline and over time. (3) To examine the relationship between changes in the characteristics of sleep slow waves (amplitude, slope, and the origin and speed of traveling waves) and neuropsychological functioning in aMCI and non-impaired Veterans over time. Study Design: This is a 4-year longitudinal, observational study of sleep and neurocognitive functioning of Veterans with aMCI as compared to a cognitively-normal control group of Veterans. All participants will undergo testing at baseline and 2 years later. Veterans (N=70), 65 years and older, will be invited to participate in the study. Two groups, Veterans meeting the criteria for aMCI (n = 41) and non-MCI controls (n = 29) (matched for age, education, race, and gender), will be enrolled. Subjects will undergo a history/physical exam, neuropsychological testing, and MRI to confirm aMCI and non-MCI status. Subjects meeting study requirements will complete questionnaires, two weeks of actigraphy/sleep diaries, and overnight hd- EEG/polysomnography at baseline. MRI, neuropsychological testing, and sleep studies will be repeated two years later. The application of hd-EEG represents significant scientific innovation in advanced neurophysiological assessment of sleep. Our findings will clarify the degree to which changes in the characteristics of sleep slow waves are due to normal aging or are evidence of early cognitive impairment. It is hoped that this line of research will ultimately lead to better clinical predictors of cognitive decline.

Public Health Relevance

There is compelling research that sleep plays a critical role in memory processes. When sleep is disrupted, memory is significantly impaired. Disrupted sleep is a common complaint of individuals with mild cognitive impairment and Alzheimer's disease. This study of sleep using EEG, and a new technology - high-density EEG, allows us to examine changes in the electrical power of the brain believed to be important to memory. The technology allows the study of these changes by simply wearing a special cap during sleep. Veterans, 65 years and older, some with and some without cognitive impairment, will spend two nights sleeping in a sleep lab setting. We anticipate that examining changes during sleep in Veterans with mild cognitive impairment, as compared with those without impairment, will clarify whether EEG changes during sleep are a symptom, risk factor, or early marker of dementia. Currently, there are nearly 600,000 Veterans with dementia. The financial costs for care alone are estimated at $19,522 annually per Veteran. The personal costs are significant.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Veterans Administration (IK2)
Project #
1IK2CX000535-01
Application #
8138225
Study Section
Mental Health and Behavioral Science B (MHBB)
Project Start
2011-10-01
Project End
2015-09-30
Budget Start
2011-10-01
Budget End
2012-09-30
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Wm S. Middleton Memorial Veterans Hosp
Department
Type
DUNS #
086683091
City
Madison
State
WI
Country
United States
Zip Code
53705