Sundowning, or sundown syndrome, [1] is a neurological phenomenon wherein people with delirium or some form of dementia experience increased confusion and restlessness beginning in the late afternoon and early evening. It is most commonly associated with Alzheimer's disease but is also found in those with other forms of dementia. The term sundowning was coined by nurse Lois K. Evans in 1987 due to the association between the person's increased confusion and the setting of the sun. [2] [3]
For people with sundown syndrome, a multitude of behavioral problems begin to occur and are associated with long-term adverse outcomes. [4] [5] [6] [7] Sundowning seems to occur more frequently during the middle stages of Alzheimer's disease and mixed dementia and seems to subside with the progression of the person's dementia. [4] [5] People are generally able to understand that this behavioral pattern is abnormal. Research shows that 20–45% of people with Alzheimer's will experience some variation of sundowning confusion. [4] [8] However, despite lack of an official diagnosis of sundown syndrome in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), there is currently a wide range of reported prevalence. [2]
The following social, economic, and physiological adverse outcomes are correlated with individuals affected by sundowning and their caregivers:
Symptoms are not limited to but may include:
While the specific causes of sundowning have not been empirically proven, some evidence suggests that circadian rhythm disruption increases sundowning behaviors. [11] In humans, sunset triggers a biochemical cascade that involves a reduction of dopamine levels and a shift towards melatonin production as the body prepares for sleep. In individuals with dementia, melatonin production may be decreased, [1] which may interrupt other neurotransmitter systems.
Other causes or precipitating factors that may lead to sundown syndrome may include hormonal changes, disturbances in REM sleep, individual and/or caregiver fatigue, inappropriate medication use, or being predisposed to behavioral disorders from chronic neurological diseases. [12] Resources in an institution's environment can also play a role as a symptom trigger. A reduced number of staff in the evening can be attributed to more unmet needs and a lower threshold for agitation for individuals with sundown syndrome. [13]
Sundowning should be distinguished from delirium, and could be presumed to be delirium when it appears as a new behavioral pattern until a causal link between sunset and behavioral disturbance is established. [14] People with established sundowning and no obvious medical illness may be suffering from impaired circadian regulation, or may be affected by nocturnal aspects of their institutional environment such as shift changes, increased noise, or reduced staffing (which leads to fewer opportunities for social interaction). Delirium is generally an acute event that can span over hours to days. [1]
It is thought that with the development of plaques and tangles associated with Alzheimer's disease there might be a disruption within the suprachiasmatic nucleus (SCN). [6] The SCN is located in the hypothalamus and is associated with regulating sleep patterns by maintaining circadian rhythms, which are strongly associated with external light and dark cues. A disruption within the suprachiasmatic nucleus would seem to be an area that could cause the types of confusion that are seen in sundowning. However, finding evidence for this is difficult, as an autopsy is needed to analyze this disruption properly. By the time a person experiencing Alzheimer's has died, they have usually surpassed the level of brain damage (and associated dementia) that would be associated with sundowning. This hypothesis is, however, supported by the effectiveness of melatonin, a natural hormone, to decrease behavioral symptoms associated with sundowning. The pineal gland produces melatonin when signaled by the SCN to help maintain circadian rhythms. Melatonin supplementation can be administered to older adults as their natural hormonal production decreases over time. [12]
Serotonin has also been observed to potentially have a key role in the regulation of circadian rhythm as research has shown that serotonergic agonism in the SCN results in "phase shifts" in portions of the light-dark cycle. [2] [15] [16] In addition to the effects on circadian rhythm, serotonin is also known to be involved in the regulation of aggression. [2] Due to the serotonergic signaling deficiencies of Alzheimer's disease, it has been commonly reported that deficiencies in serotonin have been associated with worsening circadian rhythm or aggression. [2] [17]
Elderly people often experience multiple comorbidities that may contribute to the phenomenon of sundowning syndrome through neurodegeneration.
Treatment of sundown syndrome may vary based on when agitated behavior is observed throughout the day. [20]
There are several pathways in the pipeline for scientists seeking therapeutic options for sundowning syndrome.
In addition to sundown syndrome not being officially recognized in the DSM-5, there is also the thought that sundown syndrome may be a phenomenon of caretakers' perception of patient agitation in the early afternoon to evening. [2] Some studies have observed sundown syndrome occurring at times other than sunset which may suggest the symptoms associated with sundown syndrome are time-dependent rather than occurring specifically at sundown. [2] [30]
Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia ultimately has a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process.
A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Sleep disorders are frequent and can have serious consequences on patients' health and quality of life. Polysomnography and actigraphy are tests commonly ordered for diagnosing sleep disorders.
Jet lag is a temporary physiological condition that occurs when a person's circadian rhythm is out of sync with the time zone they are in, and is a typical result from travelling rapidly across multiple time zones. For example, someone travelling from New York to London, i.e. from west to east, feels as if the time were five hours earlier than local time, and someone travelling from London to New York, i.e. from east to west, feels as if the time were five hours later than local time. The phase shift when travelling from east to west is referred to as phase-delay of the circadian cycle, whereas going west to east is phase-advance of the cycle. Most travellers find that it is harder to adjust time zones when travelling east. Jet lag was previously classified as a circadian rhythm sleep disorder.
A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.
Delirium is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or multiple causes, which usually develops over the course of hours to days. As a syndrome, delirium presents with disturbances in attention, awareness, and higher-order cognition. People with delirium may experience other neuropsychiatric disturbances including changes in psychomotor activity, disrupted sleep-wake cycle, emotional disturbances, disturbances of consciousness, or, altered state of consciousness, as well as perceptual disturbances, although these features are not required for diagnosis.
Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time and is usually diagnosed when cognitive impairment interferes with normal daily functioning. Together with Parkinson's disease dementia, DLB is one of the two Lewy body dementias. It is a common form of dementia, but the prevalence is not known accurately and many diagnoses are missed. The disease was first described on autopsy by Kenji Kosaka in 1976, and he named the condition several years later.
The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive retinal ganglion cells allow it to coordinate the subordinate cellular clocks of the body and entrain to the environment. The neuronal and hormonal activities it generates regulate many different body functions in an approximately 24-hour cycle.
Non-24-hour sleep–wake disorder is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society". Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blind, it can also affect sighted people. Non-24 may also be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) has provided CRSD guidelines since 2007 with the latest update released in 2015.
Smith–Magenis syndrome (SMS), also known as 17p-microdeletion syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, difficulty sleeping, and numerous behavioral problems such as self-harm. Smith–Magenis syndrome affects an estimated between 1 in 15,000 to 1 in 25,000 individuals.
Organic brain syndrome, also known as organic brain disease, organic brain damage, organic brain disorder (OBD), organic mental syndrome, or organic mental disorder, refers to any syndrome or disorder of mental function whose cause is alleged to be known as organic (physiologic) rather than purely of the mind. These names are older and nearly obsolete general terms from psychiatry, referring to many physical disorders that cause impaired mental function. They are meant to exclude psychiatric disorders. Originally, the term was created to distinguish physical causes of mental impairment from psychiatric disorders, but during the era when this distinction was drawn, not enough was known about brain science for this cause-based classification to be more than educated guesswork labeled with misplaced certainty, which is why it has been deemphasized in current medicine. While mental or behavioural abnormalities related to the dysfunction can be permanent, treating the disease early may prevent permanent damage in addition to fully restoring mental functions. An organic cause to brain dysfunction is suspected when there is no indication of a clearly defined psychiatric or "inorganic" cause, such as a mood disorder.
Ramelteon, sold under the brand name Rozerem among others, is a melatonin agonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset. It reduces the time taken to fall asleep, but the degree of clinical benefit is small. The medication is approved for long-term use. Ramelteon is taken by mouth.
Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep–wake disorders (CRSWD), are a family of sleep disorders that affect the timing of sleep. CRSDs cause a persistent pattern of sleep/wake disturbances that arise either by dysfunction in one's biological clock system, or by misalignment between one's endogenous oscillator and externally imposed cues. As a result of this misalignment, those affected by circadian rhythm sleep disorders can fall asleep at unconventional time points in the day, or experience excessive daytime sleepiness if they resist. These occurrences often lead to recurring instances of disrupted rest and wakefulness, where individuals affected by the disorder are unable to go to sleep and awaken at "normal" times for work, school, and other social obligations. Delayed sleep phase disorder, advanced sleep phase disorder, non-24-hour sleep–wake disorder and irregular sleep–wake rhythm disorder represents the four main types of CRSD.
Shift work sleep disorder (SWSD) is a circadian rhythm sleep disorder characterized by insomnia, excessive sleepiness, or both affecting people whose work hours overlap with the typical sleep period. Insomnia can be the difficulty to fall asleep or to wake up before the individual has slept enough. About 20% of the working population participates in shift work. SWSD commonly goes undiagnosed, and it is estimated that 10–40% of shift workers have SWSD. The excessive sleepiness appears when the individual has to be productive, awake and alert. Both symptoms are predominant in SWSD. There are numerous shift work schedules, and they may be permanent, intermittent, or rotating; consequently, the manifestations of SWSD are quite variable. Most people with different schedules than the ordinary one might have these symptoms but the difference is that SWSD is continual, long-term, and starts to interfere with the individual's life.
Melatonin receptors are G protein-coupled receptors (GPCR) which bind melatonin. Three types of melatonin receptors have been cloned. The MT1 (or Mel1A or MTNR1A) and MT2 (or Mel1B or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 (or Mel1C or MTNR1C) has been identified in amphibia and birds. The receptors are crucial in the signal cascade of melatonin. In the field of chronobiology, melatonin has been found to be a key player in the synchrony of biological clocks. Melatonin secretion by the pineal gland has circadian rhythmicity regulated by the suprachiasmatic nucleus (SCN) found in the brain. The SCN functions as the timing regulator for melatonin; melatonin then follows a feedback loop to decrease SCN neuronal firing. The receptors MT1 and MT2 control this process. Melatonin receptors are found throughout the body in places such as the brain, the retina of the eye, the cardiovascular system, the liver and gallbladder, the colon, the skin, the kidneys, and many others. In 2019, X-ray crystal and cryo-EM structures of MT1 and MT2 were reported.
Designing lighting for the elderly requires special consideration and care from architects and lighting designers. As people age, they experience neurodegeneration in the retina and in the suprachiasmatic nucleus (SCN). Less light reaches the back of the eyes because the pupils decrease in size as one ages, the lens inside one's eye becomes thicker, and the lens scatters more light, causing objects and colors to appear less vivid. These symptoms are particularly common with persons having alzheimer's disease. Older people also have reduced levels of retinal illuminance, such as having smaller pupils and less transparent crystalline lenses. Furthermore, as an individual ages, they begins to lose retinal neurons, which not only compromises the ability to see but also to register a robust daily pattern of light-dark that is needed to maintain biological rhythms. The 24-hour light-dark cycle is the most important external stimulus for regulating the timing of the circadian cycle.
Irregular sleep–wake rhythm disorder (ISWRD) is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode, and irregularity from day to day. Affected individuals have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake. The total time asleep per 24 hours is normal for the person's age. The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated.
A chronobiotic is an agent that can cause phase adjustment of the circadian rhythm. That is, it is a substance capable of therapeutically entraining or re-entraining long-term desynchronized or short-term dissociated circadian rhythms in mammals, or prophylactically preventing their disruption following an environmental insult such as is caused by rapid travel across several time zones. The most widely recognized chronobiotic is the hormone melatonin, secreted at night in both diurnal and nocturnal species.
Familial sleep traits are heritable variations in sleep patterns, resulting in abnormal sleep-wake times and/or abnormal sleep length.
Dr. Debra J. Skene is a chronobiologist with specific interest in the mammalian circadian rhythm and the consequences of disturbing the circadian system. She is also interested in finding their potential treatments for people who suffer from circadian misalignment. Skene and her team of researchers tackle these questions using animal models, clinical trials, and most recently, liquid chromatography-mass spectrometry. Most notably, Skene is credited for her evidence of a novel photopigment in humans, later discovered to be melanopsin. She was also involved in discovering links between human PER3 genotype and an extremely shifted sleep schedules categorized as extreme diurnal preference. Skene received her Bachelor of Pharmacy, Master of Science, and Ph.D. in South Africa.
Melatonin is a naturally occurring hormone produced in the brain that is also used as a dietary supplement and medication. As a hormone, melatonin is released by the pineal gland and is involved in sleep–wake cycles. As a supplement, it is often used for the attempted short-term treatment of disrupted sleep patterns, such as from jet lag or shift work, and is typically taken orally. There is evidence of its benefit for this use, but is not strong. A 2017 review found that sleep onset occurred six minutes faster with use on average, but found no change in total time asleep.