Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?

Abstract

Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals, evaluating: (i) associations and plausible mechanisms linking NREM sleep disruption, Aβ, and AD, (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation, (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD, and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.

Relationship between Cognitive and Sleep–wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer’s Disease

“…More specifically, greater sympathetic prevalence [as denoted by increased low frequency/high frequency (L/H)] at night was associated with more widespread poor results in cognition, including not only verbal memory but overall cognition (as reflected in the MMSE score) and visuospatial/executive function (clock drawing score).A potential link between abnormal sleep–wake variation and poor cognition in the present sample of O-LOAD might be the reported association between reduced parasympathetic activity and decreased sleep quality (Burton et al, 2010), which in turn predicts cognitive decline (Mander et al, 2016). Another potential link may be the increased susceptibility to stress (e.g., Stenfors et al, 2016).…”

Sleep and Human Aging

“…These bi-directional relationships are observed before the onset of disease and, furthermore, independently of sleep disorders that also increase dementia risk, such as insomnia or sleep apnea (Osorio et al, 2011; Yaffe et al, 2011). It suggests that inadequate sleep is not only a predisposing risk factor contributing to degenerative disease processes, but represents a novel treatment opportunity and/or even preventative strategy in this context (Mander et al, 2016a). In summary, dementia-related neuropathologies are associated with forms of sleep disruption that are uniquely distinct from typical age-related sleep disruption or, in some cases, a significantly more severe form of those same sleep impairments.…”

Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer’s Disease?

“…It is clear that sleep can affect the development [89] and progression [96] of AD. However, the precise way in which deregulated sleep may influence AD is not clear.…”