Sleep Disorders in Neurodegenerative Diseases with Dementia: A Comprehensive Review

Abstract

Dementia is a growing problem of global relevance, currently affecting over 55 million people worldwide. The number of new dementia cases is still increasing, primarily due to the aging of society. Dementia is defined as a substantial decline in cognitive function, and it is inherently associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, and vascular dementia. Of note, most patients suffering from neurodegenerative conditions, in addition to cognitive impairment, often experience various types of sleep disorders, including insomnia, rapid eye movement sleep behavior disorder, sleep-disordered breathing, and circadian rhythm disturbances. There is increasing evidence of a bidirectional interaction between sleep disturbances and mental health. Disrupted sleep may directly aggravate neuropsychiatric symptoms, like depression, anxiety, agitation, and hallucinations, and conversely, such symptoms can make sleeping more difficult. This creates a feedback loop that inevitably leads to disease progression and deterioration in quality of life. In this review, we provide an up-to-date overview of the nature and mechanisms behind sleep disorders in major neurodegenerative diseases, summarize treatment strategies for handling sleep disturbances, and discuss the clinical relevance of sleep-mental health interactions in the context of neurodegeneration-associated dementia. Neurodegeneration is a complex problem on the border between neurology and psychiatry, and it poses a challenge to the healthcare system, as it requires multidisciplinary approaches for optimal management. Understanding the connection between sleep and neuropsychiatric symptoms offers further opportunities for better symptom control, improved quality of life, and slower cognitive decline.

Keywords: Alzheimer’s disease; Parkinson’s disease; circadian rhythm; cognitive decline; dementia; integrated care; neurodegeneration; neuroinflammation; neuropsychiatry; sleep disorders.

Figure 1

Types of sleep disturbances in the selected neurodegenerative disorders. Neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, or frontotemporal dementia are characterized by specific sleep patterns, which are directly associated with the affected brain regions. Abbreviations: EDS—excessive daytime sleepiness; RBD—rapid eye movement sleep behavior disorder; and RLS—restless leg syndrome. Created in BioRender. Siwecka, N. (2025) https://BioRender.com/cp49vwh.

Figure 2

Neural circuitry governing wakefulness and sleep. The ascending reticular arousal system (ARAS) induces waking and alertness, whereas the hypothalamic intermediate nucleus (IntN) inhibits ARAS and thus promotes sleep. Both systems are under the influence of the suprachiasmatic nucleus (SCN), which regulates their activation levels and the switch between sleep and wakefulness. ARAS projections originate in the brainstem and extend to the cerebral cortex via the thalamus and hypothalamus. The legend presents the location of neural cell bodies for the specific neurotransmitters. LH—lateral hypothalamus; BF—basal forebrain; PAG—periaqueductal gray matter; TMN—tuberomammillary nucleus; RN—raphe nuclei; LDT—laterodorsal tegmental nucleus; PPN—pedunculopontine nucleus. Created in BioRender. Siwecka, N. (2025) https://BioRender.com/6fni0e0.

Figure 3

The molecular mechanisms underlying the effect of sleep deprivation on neurodegeneration development. Chronic sleep disturbances are associated with a number of neuropathological events, including neuroinflammatory response, increased accumulation of pathogenic proteins, loss of BBB integrity, neural cell death, disrupted neurotransmission, and hormone signaling. Such changes at the molecular level not only drive neurodegeneration and dementia symptoms but also aggravate sleep disturbances, which potentiate the sequence of pathological events in the nervous system in a positive feedback loop. Created in BioRender. Siwecka, N. (2025) https://BioRender.com/q495vp2.