Apolipoprotein E ɛ4 (APOE ɛ4) Allele is Associated with Long Sleep Duration Among Elderly with Cognitive Impairment

Abstract

Background: Apolipoprotein E gene (APOE) ɛ4 allele increases the risk for Alzheimer’s disease (AD). Furthermore, among patients with cognitive impairment, longer sleep duration is associated with worse cognitive performance. To date, literature examining the associations between APOE ɛ4 allele and objective sleep duration is limited. Objective: Our aim was to assess the association between APOE ɛ4 and objective sleep duration, among patients with mild cognitive impairment (MCI) and AD. A sub-sample of 89 patients with AD (n = 49) and MCI (n = 40) were recruited from a large, population-based cohort of 3,140 elders (>60 years) residing on Crete, Greece. Methods: All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24 h actigraphy and APOE ɛ4 allele genotyping. Comparisons of sleep duration variables between APOE ɛ4 allele carriers and non-carriers were assessed using ANCOVA, controlling for confounders. Results: The sample included 18 APOE ɛ4 carriers and 71 non-carriers, aged 78.6±6.6 and 78.2±6.5 years, respectively. Comparisons between the APOE ɛ4 carriers and non-carriers revealed no significant differences in terms of demographic and clinical variables. In terms of objective sleep duration across the two groups, APOE ɛ4 carriers compared to non-carriers had significantly longer nighttime Total Sleep Time (nTST) (7.7±1.4 versus 7.2±1.3 h, respectively, p = 0.011), as well as 24 h TST (8.5±1.6 versus 7.8±1.5 h, respectively, p = 0.012). Conclusion: Among patients with MCI and AD, APOE ɛ4 carriers have longer objective nighttime and 24 h sleep duration compared to non-carriers. These findings further support that objective long sleep duration is a genetically-driven pre-clinical marker associated with worse prognosis in elderly with cognitive impairment.

Poor Diet, Long Sleep, and Lack of Physical Activity Are Associated with Inflammation among Non-Demented Community-Dwelling Elderly

“…We propose that adopting a diet rich in vegetables and a physically active lifestyle, by lowering inflammation, could help reduce mortality and morbidity, including cognitive decline among elderly. Furthermore, given that long sleep seems to relate with inflammation levels, as well as cognition and disease severity among elders with cognitive decline [ 42 , 43 , 86 ], we and others have previously reported that treatment with sedative/sleep-prolonging psychotropic medication in this population should be given with caution [ 42 , 43 , 86 , 87 ]. These simple practical recommendations could be easily applied in a primary care setting.…”

Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype

“…Thus, this might explain the markedly strong association between insomnia symptoms and cognitive performance in this high‐risk group, in which ongoing neurodegeneration processes in APOE ε4 allele carriers could lead to both impaired memory performance and insomnia symptoms. Previous studies have shown that APOE ε4 allele carriers presented with sleep characteristics consistent with insomnia (i.e., insomnia itself, shorter sleep duration, more awakenings, and self‐reported daytime and sleep disturbances), 45–48 although sleep disturbances of a different nature have been reported in carriers as well (i.e., longer sleep duration) 49 …”

“…Previous studies have shown that APOE ε4 allele carriers presented with sleep characteristics consistent with insomnia (i.e., insomnia itself, shorter sleep duration, more awakenings, and selfreported daytime and sleep disturbances), [45][46][47][48] although sleep disturbances of a different nature have been reported in carriers as well (i.e., longer sleep duration). 49 To our knowledge, only one previous study evaluated whether the APOE genotype interacts with insomnia to predict brain health outcomes. In cognitively healthy older adults, Grau-Rivera et al found that the presence of insomnia was associated with worse delayed memory recall in APOE ε4 carriers only, while in non-carriers, insomnia was associated with worse working memory.…”

Non-Pharmacological Treatments of Neuropsychiatric Symptoms in Mild Cognitive Impairment

“…17 Sleep disturbances, particularly sleeping longer, have been associated with more severe cognitive impairment and worse prognosis in individuals with MCI, 18 especially in APOέ4 carriers. 19 Reduced medial temporal lobe volume was shown to be related to sleep disturbances but no other psychiatric symptoms in older adults with MCI, 20 suggesting that sleep pattern could be a clinical biomarker of AD and a target for dementia risk reduction. In non-amnestic MCI, the relationship between sleep-wake disturbance and cognitive functioning could suggest shared neurobiological underpinnings.…”