Alzheimer's And Sleep: Understanding The Complex Relationship

Sleep problems are a common issue for people with Alzheimer's disease, with insomnia affecting one-fourth to one-third of patients with dementia. The condition can cause distress for both the patient and their caretaker, and can even lead to early institutionalisation. Alzheimer's patients may experience excessive daytime sleepiness, sleep-disordered breathing, restless leg syndrome, and REM sleep disorders. These issues can be difficult to manage and may require a combination of lifestyle changes, medication, and support from specialists and caregivers.

Insomnia

Several studies have found a link between insomnia and Alzheimer's disease. Sleep deprivation and insomnia can induce the aggregation of amyloid-beta peptides and tau proteins, which are the hallmark pathological features of Alzheimer's disease. Insomnia can also cause an increase in the levels of amyloid-beta in the cerebrospinal fluid, leading to synaptic dysfunction and impaired neurotransmission, which are critical to the development of Alzheimer's disease.

In addition to its effects on amyloid-beta and tau proteins, insomnia has also been associated with increased inflammation in the brain. This may further contribute to the progression of Alzheimer's disease. Chronic inflammation and increased levels of certain inflammatory markers have been observed in individuals with insomnia, which may impact the brain and cognitive function.

The impact of insomnia on Alzheimer's disease is not limited to biochemical processes but also extends to cognitive functioning. Insomnia has been linked to a higher risk of cognitive decline, particularly in older adults who are already at risk for Alzheimer's disease. The disruption of sleep patterns can negatively affect cognitive functions such as memory and attention.

Furthermore, insomnia may also contribute to the breakdown of the blood-brain barrier, which plays a crucial role in maintaining brain health by restricting the permeability of the brain endothelium layer. Sleep deprivation and insomnia can lead to changes in cellular components of the blood-brain barrier, increasing its permeability and potentially exacerbating the effects of Alzheimer's disease.

Overall, insomnia can have far-reaching consequences for individuals with Alzheimer's disease, affecting not only their sleep but also their cognitive functions and brain health. Understanding the role of insomnia in Alzheimer's disease may provide opportunities for prevention and treatment in the future.

Excessive daytime sleepiness

Research has also found a link between excessive daytime sleepiness and the presence of beta-amyloid, the protein that clumps in the brain as part of Alzheimer's pathology. A study published in the journal Sleep found that older adults who experienced excessive daytime sleepiness were nearly three times more likely to have deposits of beta-amyloid in their brains. This suggests that sleep problems and Alzheimer's pathology may be connected, although the exact mechanism remains unclear.

It is important to note that excessive daytime sleepiness can also be caused by other factors, such as sleep disorders like sleep apnea, medications, or other health conditions. If excessive daytime sleepiness is a concern, it is recommended to consult a healthcare professional to rule out any underlying causes and determine if further evaluation for Alzheimer's disease or related dementias is necessary.

While there is currently no cure for Alzheimer's disease, prioritizing sleep quality and treating sleep issues may be one way to help prevent or slow down the progression of the disease. This can include targeting sleep disorders, such as insomnia and sleep apnea, as well as addressing social and individual factors that may impact sleep, such as work or excessive TV watching.

Sleep-disordered breathing

• Obstructive sleep apnea (OSA), the most common form, where the upper airway either partially or fully collapses during inspiration.
• Central sleep apnea, where respiratory rhythm-generating neurons in the brainstem fail to send sufficient signals to upper airway pharyngeal dilator muscles and chest wall respiratory pump muscles.
• Mixed or complex sleep apnea, which involves a combination of both obstructive and central apneas.

OSA is associated with an increased risk of developing cognitive decline and dementia, including Alzheimer's disease (AD). Studies have found that over 50% of patients with AD experience SDB. SDB is thought to contribute to large amyloid plaque loads, a hallmark of AD pathology.

SDB can cause intermittent hypoxia (IH), which can lead to several morbidities, including cardiovascular remodelling, metabolic disorder, sympathetic nervous system hyperactivation, and cognitive impairments. IH exposure has been shown to increase cerebral and hippocampal amyloid beta (Aβ) burden and induce tau hyperphosphorylation, both of which are pathologic hallmarks of AD.

Animal models have been developed to study the effects of IH and sleep fragmentation on AD pathology. These models have shown that IH alone can recapitulate most of the OSA-associated morbidities observed in humans. Additionally, sleep fragmentation, a common co-morbidity of IH, can also lead to negative consequences such as hypertension and metabolic disturbances.

Restless legs syndrome

Restless leg syndrome (RLS) is a sensorimotor sleep-related movement disorder characterised by an "urge to move the legs" and an "unpleasant sensation". Symptoms tend to begin or worsen during periods of rest, particularly in the evening or at night. RLS is associated with sleep-onset or sleep-maintenance insomnia, depression, anxiety, and other conditions.

A retrospective cohort study found that RLS is associated with an increased risk of incident all-cause dementia in older adults. The study, which used the Korean National Health Insurance Service-Elderly Cohort (aged 60 and above), observed that the incidence of all-cause dementia was higher in the RLS group than in the control group (10.4% vs 6.2%).

RLS is associated with several risk factors for dementia, including poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia. However, the relationship between RLS and incident dementia remains unclear and requires further confirmation through prospective studies.

REM sleep behavioural disorder

REM sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of muscle paralysis during REM sleep, allowing people to physically act out their dreams. This can include violent or dangerous behaviours such as grabbing, jumping out of bed, screaming, kicking, and punching, which can cause injury to the patient or their bed partner. RBD is usually treatable with medication.

RBD is a strong predictor of neurodegeneration, and people with the condition are very likely to develop a brain disease. Autopsies of RBD patients have revealed that clumps of proteins, known as alpha-synuclein aggregates, congregate in the regions of the brain that regulate REM sleep. As many as 80-90% of people with RBD will develop a brain disease, most often Parkinson's disease, Lewy body dementia (LBD), or multiple system atrophy.

While Alzheimer's Disease (AD) is reported as a possible development in patients with RBD, it occurs in a limited number of cases (7-11% of cases according to longitudinal studies). There are concerns about the accuracy of the diagnostic criteria, as the clinical features and neuropathology of AD and LBD overlap. Further studies are needed to investigate the association between RBD and AD, using updated diagnostic criteria and ancillary investigations.

The strong link between RBD and neurodegeneration has led researchers to suggest that cognitive decline may first affect the areas of the brain that control sleep, which would explain the high incidence of sleep disorders in Alzheimer's patients. Sleep studies have shown that the internal clock of Alzheimer's patients functions properly, but there is something else occurring in the brain that causes patients to sleep and wake randomly.

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