The Emerging Role of Sleep in the Development of Alzheimer Disease
More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).
Experts predict estimated costs related to AD to be more than $500 billion annually starting in 2040 (Hurd MD, et al. N Engl J Med. 2013;368[14]:1326). AD is a neurodegenerative disorder characterized by gradual, progressive decline in memory along with other cognitive functions, eventually leading to impairment in activities of daily living. Most current treatments for AD are symptomatic and only minimally slow progression of disease. The increasing prevalence, overwhelming costs to society, and the absence of a cure for AD have created an impending national health crisis.
As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).
However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
Poor Sleep as a Risk Factor for Alzheimer Disease
Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.
Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with
