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The incidence of sleep disorders, particularly sleep deprivation (SD), increases with age and is prevalent in neurodegenerative and psychiatric disorders such as Alzheimer\u2019s disease (AD). Nearly 40% of AD patients experience significant chronic sleep impairments. The clinical distinction between late-life sleep disorders and AD is often challenging due to overlapping symptoms, including cognitive decline and behavioral impairments. Although the exact causal relationship between SD and AD remains complex and multifaceted, strong evidence suggests a bidirectional link, with AD patients frequently exhibiting disrupted sleep architecture, reduced slow-wave activity, and shorter total sleep duration. On a pathophysiological level, SD contributes to neuroinflammation, amyloid-\u03b2 plaque deposition, and tau tangles, which are key features of AD. Current treatments, such as sedatives and antidepressants, often have limitations, including inconsistent efficacy, dependency risks, and poor long-term outcomes\/recurrence, highlighting the need for safer and more effective alternatives. This review examines the interplay between SD and AD and proposes omega (n)-3 fatty acids (FAs) as a potential therapeutic intervention. Preclinical and clinical studies suggest that n-3 supplementation may improve sleep onset\/quality, reduce neuroinflammation, support synaptic function, and decrease amyloid-\u03b2 aggregation, thereby alleviating early AD-related neurological changes. Given their safety profile and neuroprotective effects, n-3 FAs represent a promising strategy for managing the comorbidity of sleep disorders in AD.<\/jats:p>","DOI":"10.3390\/brainsci15060641","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T10:47:22Z","timestamp":1750070842000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sleep Deprivation and Alzheimer\u2019s Disease: A Review of the Bidirectional Interactions and Therapeutic Potential of Omega-3"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-8581","authenticated-orcid":false,"given":"Nasar Ullah Khan","family":"Niazi","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Institute of Marine Drugs and Nutrition, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Ou","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiye","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-684X","authenticated-orcid":false,"given":"Zhiyou","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Institute of Marine Drugs and Nutrition, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2017.02.004","article-title":"Sleep and Human Aging","volume":"94","author":"Mander","year":"2017","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102514","DOI":"10.1016\/j.arr.2024.102514","article-title":"Sleep Disorders and Risk of Alzheimer\u2019s Disease: A Two-Way Road","volume":"101","author":"Lacerda","year":"2024","journal-title":"Ageing Res. 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