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

Background: The Apolipoprotein (APOE) epsilon 4 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 epsilon 4 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 epsilon 4. Amongst female subjects with high AD load and Lewy body pathology, homozygous (epsilon 4/epsilon 4) carriers experienced disrupted sleep more often compared with heterozygous (epsilon 4/x) or non-carriers of epsilon 4. Such recessive, gender-specific, and Lewy body association is reminiscent of the epsilon 4 effect on psychosis in AD. However, such association was lost after adjusting for covariates. In subjects with no to low AD pathology, female epsilon 4 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 epsilon 4 on sleep disturbances is dependent on gender and severity of AD load.