Alzheimer disease: Genetic Risk Mitigated by Good Sleep Interview with:
Assistant Professor and Clinician Scientist
Division of Neurology, Department of Medicine
Sunnybrook Health Sciences Centre
University of Toronto What are the main findings of the study?

Dr. Lim: Alzheimer disease (AD) is the result of a confluence of genetic, behavioral, and environmental risk factors.  The Apolipoprotein E (APOE) e4 allele is the most common and well established genetic risk factor for Alzheimer Disease.  10-20% of the US population carries the high risk APOE e4 allele, which confers up to a 30% lifetime risk of AD. Meanwhile, previous work had suggested that poor sleep may be a risk factor for AD and that APOE genotype and poor sleep may amplify each other’s negative cognitive effects.

We asked the question whether good sleep consolidation (i.e. sound sleep without repeated awakenings) may reduce the effect of APOE on the risk of incident AD and the burden of AD pathology.  We studied 698 individuals without dementia participating in the Rush Memory and Aging Project – a longitudinal cohort study of aging and risk factors for AD.  We measured sleep consolidation using wrist-watch like devices called actigraphs, and followed participants for up to 6 years, examining them annually for the development of AD.  Autopsies were perfumed on 201 participants who died during the follow-up period and we quantified the burden of AD pathology.

During the follow-up period, 98 participants developed AD.  As expected, carrying the APOE e4 allele was associated with a higher risk of AD, faster cognitive decline, and a higher burden of AD pathology (amyloid plaques and neurofibrillary tangles) at death. However, better sleep at baseline significantly reduced the negative impact of APOE e4 on the risk of AD, rate of cognitive decline, and burden of neurofibrillary tangle pathology. Were any of the findings unexpected?

Dr. Lim: These results highlight a heretofore  unappreciated link between sleep, APOE, neurofibrillary tangle biology, and dementia. What should clinicians and patients take away from your report?

Dr. Lim: First, these results suggest that even among APOE e4 carriers, there is a subset of individuals with excellent sleep consolidation who may be at a reduced risk of AD, and on the other hand, there is a subset of individuals with very poor sleep who may be at a particularly high risk of AD.  Second, these results raise the possibility that interventions to enhance sleep consolidation (whether by diagnosing and treating sleep disorders, using pharmacological interventions, or environmental interventions such as noise reduction) may potentially be a useful way to decrease AD risk in APOE e4 carriers. What recommendations do you have for future research as a result of this study?

Dr. Lim: Future interventional studies will help to further define the appropriate role for genotyping, sleep assessment, and sleep interventions in the clinical management of individuals at risk for AD.


Modification of the Relationship of the Apolipoprotein E ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density by Sleep

Lim AS, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA.

JAMA Neurol. 2013 Oct 21. doi: 10.1001/jamaneurol.2013.4215. [Epub ahead of print]
PMID: 24145819 [PubMed – as supplied by publisher]

Last Updated on October 24, 2013 by Marie Benz MD FAAD