Cooper Lueck

Background: Alzheimer’s Disease (AD) is currently the most common neurodegenerative disease in the United States and is the sixth leading cause of death for Americans.^1,2 The disease also has a global health expenditure greater than 1 trillion USD annually.¹ Despite the gravity of this disease and the amount of capital dedicated to combating its effects, currently approved treatment methods are scarce that can affect the progression of the disease, rather than just treating the symptoms.

AD is defined by two main lesion types: positive and negative. Positive lesions are characterized by accumulations of amyloid beta protein, neurofibrillary tangles, dystrophic neurites, etc.¹ Negative lesions, conversely, are characterized by widespread atrophy, neuronal loss, and synaptic loss that initially localize to the medial temporal lobe. This area of the brain is also notable for its close proximity to areas of the brain responsible for wakefulness and sleep signalling.³ Therefore, the focus of this current research was to better understand how the etiology of AD related to an observed phenomena in AD patients, poor sleep.

Objective: In this review of existing literature involving sleep and AD, I sought to understand the bidirectional mechanisms between these two concepts and how improving sleep might slow or even halt the onset of AD.

Search Methods: An online search of the online database, PubMed, was performed. Papers published between 2017 and 2023 were included and search results were focused using keywords including: “Alzheimer’s,” “sleep,” and “therapeutics.”

Results: Previous studies have demonstrated that sleep worsens with age.⁴ Further, recent studies have also demonstrated that poor sleep quality can have a significant impact on an individual’s burden of AD biomarkers.^{5, 6, 7, 8} This burden has been demonstrated after just a single night of sleep deprivation.^{5, 6, 8} Unfortunately, methods previously shown to improve sleep quality and cognitive function (aromatherapy and massage) in healthy individuals did not translate to patients with AD.^{9, 10} Several other studies have demonstrated clinically relevant improvements in AD biomarker burden and cognitive function through the use of pharmaceuticals and brain stimulation techniques.^{6, 11, 12}

Conclusion: Despite the exciting results of these studies, research into the effects of sleep on AD and vice versa is not nearly as common as other areas in literature. Unlike these other preventative measures such as diet, exercise, education, etc. that may be difficult or inaccessible to some individuals, sleep is something that all humans must do. A better understanding of the interplay between AD and sleep is crucial to the development of preventative methods. Therefore, current guidelines for AD screenings should utilize sleep quality questionnaires and additional funding should be made available to better study how sleep could impact the development and progression of AD in order to better develop therapeutics for the disease.

Works Cited:

1. Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules. 2020;25(24):5789. doi:10.3390/molecules25245789
2. Atri A. The Alzheimer’s Disease Clinical Spectrum: Diagnosis and Management. Medical Clinics of North America. 2019;103(2):263-293. doi:10.1016/j.mcna.2018.10.009
3. Brain Basics: Understanding Sleep. National Institute of Neurological Disorders and Stroke. Accessed May 8, 2023. https://www.ninds.nih.gov/health-information/public-education/brain-basics/brain-basics-understanding-sleep#:~:text=Clusters%20of%20sleep%2Dpromoting%20neurons,%2C%20muscle%20relaxation%2C%20and%20sedation.
4. Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-Analysis of Quantitative Sleep Parameters From Childhood to Old Age in Healthy Individuals: Developing Normative Sleep Values Across the Human Lifespan. Sleep. 2004;27(7):1255-1273. doi:10.1093/sleep/27.7.1255
5. Shokri-Kojori E, Wang GJ, Wiers CE, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci USA. 2018;115(17):4483-4488. doi:10.1073/pnas.1721694115
6. Barthélemy NR, Liu H, Lu W, Kotzbauer PT, Bateman RJ, Lucey BP. Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid. Ann Neurol. 2020;87(5):700-709. doi:10.1002/ana.25702
7. Ju YES, McLeland JS, Toedebusch CD, et al. Sleep Quality and Preclinical Alzheimer Disease. JAMA Neurol. 2013;70(5):587. doi:10.1001/jamaneurol.2013.2334
8. Roh JH, Huang Y, Bero AW, et al. Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology. Sci Transl Med. 2012;4(150). doi:10.1126/scitranslmed.3004291
9. Kim YJ, Kim HR, Jung YH, Park YH, Seo SW. Effects of Electrical Automatic Massage on Cognition and Sleep Quality in Alzheimer’s Disease Spectrum Patients: A Randomized Controlled Trial. Yonsei Med J. 2021;62(8):717. doi:10.3349/ymj.2021.62.8.717
10. Kouzuki M, Kitao S, Kaju T, Urakami K. Evaluation of the effect of aroma oil as a bath salt on cognitive function. Psychogeriatrics. 2020;20(2):163-171. doi:10.1111/psyg.12481
11. Zhou X, Wang Y, Lv S, et al. Transcranial magnetic stimulation for sleep disorders in Alzheimer’s disease: A double-blind, randomized, and sham-controlled pilot study. Neuroscience Letters. 2022;766:136337. doi:10.1016/j.neulet.2021.136337
12. Herring WJ, Ceesay P, Snyder E, et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer’s disease dementia and insomnia: a randomized trial. Alzheimer’s & Dementia. 2020;16(3):541-551. doi:10.1002/alz.12035