African-Americans (AAs) have an increased prevalence of Alzheimer's disease (AD) compared to whites, which traditionally has been associated to the presence of vascular disease. However, a recent community- based study of non-demented elderly, as well as our preliminary data, suggest that AAs have higher amyloid burden after adjusting for vascular risk factors, which points to the presence of additional genetic or physiological differences on AD-risk by race. The purpose of this study is to test whether poor slow wave sleep (SWS) is one of these factors. Sleep disturbances vary between AAs and non-Hispanic whites. AAs take longer to fall asleep, have shorter sleep duration, lower sleep efficiency and, more characteristically, less SWS duration when compared to whites. Relatedly, amyloid positive healthy elderly, as well as those with mild cognitive impairment (MCI) and AD, experience more sleep fragmentation and more decreased SWS and REM sleep duration than their healthy counterparts. This suggests: i) that disturbed sleep contributes to AD- neurodegeneration (or that sleep is particularly sensitive to amyloid deposition); and, ii) that race-related sleep differences might contribute to the reported increases in amyloid burden in AAs. The study has two goals: first, to confirm that black race is associated in vivo with longitudinal increases in amyloid-PET uptake and cognitive decline; second, to demostrate that poor SWS at baseline is associated with these increases after controling for the cardiovascular morbidity that is shared between sleep disturbances and dementia and might confound these associations. In consultation with community stakeholders, we will recruit 150 cognitively normal AA elderly (ages 55-75 years) and 60 whites balanced by age, sex, BMI, education and other socio- demographic variables and from the same Brooklyn neighborhoods. Visit one will include a full clinical evaluation, neuropsychological tests and clinical labs. Participants will later undergo home monitoring for OSA for two nights followed by 5 days of actigraphy. Subjects with normal sleep breathing will be invited to perform 2 nights of nocturnal polysomnography (NPSG) followed by a second final visit in which amyloid load and cerebrovascular morbidity will be analyzed by 11C-PiB PET-MR. All subjects will be invited to repeat both visits after 30 months. This study has the potential to identify clinical predictors of amyloid burden in cognitively normal AA elderly and would be an important step towards the prevention of dementia in the black community as well as the reduction of health inequities.

Public Health Relevance

Recent evidence suggests that older African-Americans (AAs) are at a higher risk of developing amyloid deposition independently of vascular disease, which would partially account for the increased prevalence of dementia among AAs. In this proposal, we will extend our prior work in this population to test whether poor slow wave sleep (SWS), which is more common among AAs when compared to whites, is one of the factors that explains these associations. This study has the potential to identify clinical (and treatable) predictors of amyloid burden in cognitively normal AA elderly and would be an important step towards the prevention of dementia in the black community as well as the reduction of health inequities.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG056531-03
Application #
9936352
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mackiewicz, Miroslaw
Project Start
2018-09-01
Project End
2023-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016