Sleep Quality and Preclinical Alzheimer Disease

Abstract

Quiz Ref ID Sleep-wake problems are common in Alzheimer disease (AD). Brain regions and pathways important for sleep and wake mechanisms are affected early in AD.^1,2 Sleep-wake abnormalities such as “sundowning”³ and nocturnal wandering frequently underlie the need for institutionalization.⁴ In mild to moderate AD, sleep-wake disturbances such as increased inadvertent daytime napping and insomnia at night affect 25% to 40% of patients with AD and their caregivers.^5,6 Even in mild cognitive impairment, or very mild dementia, there are abnormalities in sleep architecture and electroencephalography measures.⁷ What is not known is whether sleep abnormalities are present in the earliest stages of AD, prior to the manifestation of any cognitive impairment. Quiz Ref ID The pathological changes underlying AD are estimated to begin 10 to 20 years before any cognitive symptoms appear, with the earliest identifiable preclinical stage of AD being the accumulation of amyloid plaques in the brain.⁸ β-Amyloid (Aβ) is a 37–to 43–amino acid peptide produced constantly in the brain in a soluble form. When Aβ aggregates in the brain, it forms insoluble amyloid plaques. Amyloid plaques are a pathological hallmark of AD, and since they sequester soluble Aβ42, a decline in cerebrospinal fluid (CSF) Aβ42 signifies the presence of amyloid plaques.^9-12 Longitudinal studies in sporadic AD, as well as dominantly inherited AD, have demonstrated that low Aβ42 levels precede cognitive symptoms of AD by 15 years or more.^13,14 In a mouse model of Aβ and amyloid accumulation, sleep-wake cycles became highly fragmented following formation of amyloid plaques.¹² To our knowledge, there are no human studies directly assessing the potential association between sleep and AD during the comparable preclinical stage of AD, when amyloid plaques are forming but individuals are cognitively normal.