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. 2019;16(3):243-250.
doi: 10.2174/1567205016666190103161034.

Abnormal Sleep Behaviours Across the Spectrum of Alzheimer's Disease Severity: Influence of APOE Genotypes and Lewy Bodies

Ka Yi G Koo  1 , Tom A Schweizer  1   2   3   4   5 , Corinne E Fischer  1   2   6 , David G Munoz  1   7   8
Affiliations

Abnormal Sleep Behaviours Across the Spectrum of Alzheimer's Disease Severity: Influence of APOE Genotypes and Lewy Bodies

Ka Yi G Koo et al. Curr Alzheimer Res. 2019.

Abstract

Background: The Apolipoprotein (APOE) ε4 allele is a well-known risk factor for Alzheimer's Disease (AD), and sleep disturbances are commonly associated with AD. However, few studies have investigated the relationship between APOE ε4 and abnormal sleep patterns (N+) in AD.

Objective: To examine the relationship between APOE genotype, Lewy body pathology, and abnormal sleep patterns in a large group of subjects with known AD load evaluated upon autopsy.

Method: Data from 2,368 cases obtained from the National Alzheimer's Coordinating Centre database were categorized as follows: Braak Stage V/VI and CERAD frequent neuritic plaques as high load AD, Braak Stage III/IV and moderate CERAD as intermediate load AD, and Braak Stage 0/I/II and infrequent CERAD as no to low load AD. Cases discrepant between the two measures were discarded.

Results: Disrupted sleep was more frequent in males (42.4%) compared to females (35.1%), and in carriers (42.3%) as opposed to non-carriers (36.5%) of ε4. Amongst female subjects with high AD load and Lewy body pathology, homozygous (ε4/ε4) carriers experienced disrupted sleep more often compared with heterozygous (ε4/x) or non-carriers of ε4. Such recessive, gender-specific, and Lewy body association is reminiscent of the ε4 effect on psychosis in AD. However, such association was lost after adjusting for covariates. In subjects with no to low AD pathology, female ε4 carriers had significantly more nighttime disturbances than non-carriers; this effect is independent of the presence of Lewy body pathology.

Conclusion: The influence of APOE ε4 on sleep disturbances is dependent on gender and severity of AD load.

Keywords: Alzheimer's Disease; Lewy bodies; apolipoprotein E; gender; neuropathology; risk factors; sleep behaviours..

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Conflict of interest statement

Conflict of Interest:

The author(s) confirm that this article content has no conflict of interest.

Figures

Figure 1.
Figure 1.
Flow diagram depicting the selection and number of neuropathologically confirmed cases of AD within each diagnostic sub-group. NPI-Q: Neuropsychiatric Inventory Questionnaire Quick version. NAD: no/low AD load; IAD: intermediate AD load; HAD: high AD load. +/−: presence/absence. N: abnormal sleep behaviours.
See this image and copyright information in PMC

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