Lim AS, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA.
Modification of the Relationship of the Apolipoprotein E ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density by Sleep.
JAMA Neurol. 2013 Oct 21;
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The data in the Spira et al. paper are intriguing and support the idea that the deposition of Aβ is linked with abnormal sleep (in this case shorter sleep). It is interesting that this abnormality could be picked up by a sleep questionnaire without a direct measure of sleep with either actigraphy or sleep studies. It demonstrates the usefulness of such questionnaires in sleep research. It will be important to validate this type of result with electroencephalography-based measures of sleep. This paper supports our recent findings (Ju et al., 2013), as well as work in mouse models of amyloid deposition (Kang et al., 2009, and Roh et al., 2012).
The study by Lim et al. was a longitudinal study assessing hundreds of individuals in the Rush Memory and Aging project. Interestingly, better sleep consolidation, a measure of sleep quality derived from actigraphy, attenuated the effect of ApoE4 on progression to dementia and AD neuropathology. This is some of the first human evidence that sleep quality, probably distinct from a sleep disorder such as sleep apnea, may impact risk of dementia. As the participants did not have sleep studies of assessment for sleep disorders, we don’t know the contribution of those factors, nor do we know if AD pathology prior to cognitive decline may have been causing decreased sleep consolidation. The researchers did control for medications and other co-morbidities supporting the idea that better sleep consolidation is protective. This paper should prompt further studies to better understand how sleep and ApoE may interact to influence not just dementia but the underlying mechanisms such as via Aβ, tau, or the connection between the two.
Ju YE, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM.
Sleep quality and preclinical Alzheimer disease.
JAMA Neurol. 2013 May 1;70(5):587-93.
Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM.
Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.
Science. 2009 Nov 13;326(5955):1005-7.
Roh JH, Huang Y, Bero AW, Kasten T, Stewart FR, Bateman RJ, Holtzman DM.
Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer's disease pathology.
Sci Transl Med. 2012 Sep 5;4(150):150ra122.