Based on PubMed | Is fatigue a common symptom of Alzheimer's disease, and what factors typically contribute to it?

Overview

Fatigue (feeling unusually tired, low energy, or “worn out”) is not one of the hallmark cognitive symptoms of Alzheimer’s disease (AD), but it is fairly common in people living with AD, especially as the condition progresses. ^[1] Sleep problems and circadian rhythm disruption are frequent in AD and often drive daytime sleepiness and fatigue, affecting both the individual and caregivers. ^{[1] [2]} Fatigue can arise from multiple, overlapping factors, including sleep disturbances, medical comorbidities, mood changes, medication effects, reduced activity, and the underlying brain changes of AD. ^{[3] [4]}

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How Common Is Fatigue in Alzheimer’s?

• Sleep-related issues are common in AD and include excessive daytime sleepiness, difficulty falling or staying asleep, frequent night awakenings, early morning awakenings, and, in some, inversion of the sleep–wake cycle. ^{[1] [2]}
• These sleep problems increase with disease severity, and they are a major reason for caregiver stress and earlier institutionalization in some cases. ^{[1] [2]}

While studies often report “excessive daytime sleepiness” rather than using the term “fatigue,” the two are closely linked in day-to-day life; the high prevalence of sleep problems in AD makes fatigue relatively common. ^{[1] [2]}

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Key Contributors to Fatigue

Sleep Disruption and Circadian Changes

• AD is frequently associated with fragmented nighttime sleep, shorter total sleep time, and increased daytime napping. This pattern leads to nonrestorative sleep and fatigue. ^{[2] [5]}
• “Sundowning” (late afternoon/evening confusion, restlessness, anxiety) can worsen night wandering and sleep disruption, further exacerbating next‑day fatigue. ^[6]
• Age‑related changes in sleep needs, low evening lighting, unfamiliar environments, pain, hunger, or thirst can also worsen sleep quality and increase fatigue. ^[7]

Sleep Apnea and Other Sleep Disorders

• Obstructive sleep apnea (OSA) is more common in people with AD and can cause repeated pauses in breathing overnight, leading to daytime sleepiness and fatigue. ^[8] Clinicians should also consider restless legs syndrome in those reporting excessive sleepiness. ^[2]

Medical Comorbidities

• Individuals with AD frequently have additional medical conditions (e.g., vascular disease and risk factors, thyroid disorders, osteoporosis, glaucoma), and some of these can directly or indirectly contribute to fatigue. ^{[9] [4]}
• Depression is common and can degrade sleep quality and lower daytime energy. ^[5]

Medications and Polypharmacy

• Sedative‑hypnotics and certain medications used for behavior or sleep can fragment sleep, increase daytime sleepiness, and aggravate fatigue. ^[5]
• Some antidepressants (for example, venlafaxine, fluoxetine, bupropion) may be activating or disrupt sleep, potentially worsening insomnia and daytime tiredness in some individuals. ^[10]

Reduced Physical Activity and Deconditioning

• As AD progresses, people may become less active or spend more time in bed; low daytime activity and frequent naps are linked to more fragmented sleep and next-day fatigue. ^[5] Regular movement and exercise are recommended to help improve sleep and energy. ^[11]

Biological Mechanisms

• AD involves brain protein dysfunction and neuronal loss, with complex interactions among genetic, lifestyle, and environmental factors over time; these changes can affect sleep‑wake regulation and energy. ^{[12] [13]}
• Broader biological contributors to fatigue include neuroimmune and mitochondrial mechanisms (oxidative stress, hypoperfusion, reactive oxygen/nitrogen species) that can disturb neural networks involved in motivation and energy regulation, offering plausible pathways for fatigue in chronic brain conditions. ^{[14] [15] [16]}

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Practical Management Strategies

Address Sleep Problems

• Treat coexisting conditions like depression, sleep apnea, or restless legs syndrome to improve sleep and reduce fatigue. ^{[17] [2]}
• Establish a consistent routine for waking, meals, activity, and bedtime to stabilize the body’s “clock.” ^[17]
• Limit stimulants (caffeine, alcohol, nicotine), especially later in the day; avoid screens at night. ^[17]
• Increase daytime movement (walks, chair exercises, gentle resistance), which can help consolidate nighttime sleep and boost daytime energy. ^{[18] [11]}
• Manage naps by keeping them short and earlier in the day to reduce nighttime wakefulness. ^[18]
• Create a calming evening environment with soothing music or reading and comfortable room temperature and lighting. ^{[18] [7]}

Review Medications

• Have a clinician review all medications, including over‑the‑counter sleep aids, to minimize agents that worsen insomnia or daytime sleepiness and to reduce polypharmacy. ^{[10] [5]}

Maintain Overall Health

• Support general health: adequate hydration, balanced nutrition, and management of chronic conditions like high blood pressure or hearing loss can improve daytime functioning and energy. ^{[11] [19]}
• Physical exercise and social activity are important components of AD care and can help alleviate fatigue through better sleep and mood. ^[20]

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When to Seek Medical Evaluation

Consider discussing fatigue with a healthcare professional if any of the following apply:

• New or worsening daytime sleepiness or fatigue, especially with loud snoring, witnessed apneas, or morning headaches (possible OSA). ^[8]
• Significant changes in mood, interest, or appetite suggesting depression. ^[5]
• Frequent night wandering, agitation, or severe sleep fragmentation impacting safety or caregiver strain. ^{[6] [2]}
• Medication changes coinciding with new sleep problems or daytime tiredness. ^[10]

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Key Takeaways

• Fatigue is commonly experienced in Alzheimer’s, largely driven by sleep disturbances, comorbid conditions (including sleep apnea and depression), medication effects, reduced activity, and the underlying neurobiology of AD. ^{[1] [2] [4]}
• Improving sleep quality, reviewing medications, treating comorbidities, and increasing daytime activity can meaningfully reduce fatigue in many people living with AD. ^{[17] [18] [11] [2]}