A Case of Sundowning: Examining the Underlying Cause

An 80-year-old woman with a medical history of hypertension, coronary artery disease (CAD), and mild cognitive dysfunction presents to the emergency department (ED) in the early evening with chest pain. The chest pain lasted several minutes, resolved spontaneously, and was described as substernal pressure that radiated into her neck. The symptoms began while she was doing light activity around the house. 

The patient has no history of shortness of breath, diaphoresis, gastrointestinal symptoms, back pain, leg swelling, or claudication. She has no history of previous myocardial infarction or cardiac intervention/procedure. The patient takes losartan-hydrochlorothiazide for hypertension. Further history and chart auditing shows that she has atherosclerotic disease in her larger coronary arteries and she is managed by cardiology with atorvastatin, metoprolol, and aspirin. 

Her vital signs and examination in the ED are normal, including her neurologic exam. She is awake, alert, and oriented. Her husband is present and witnessed the start of her symptoms. Her complete blood count and basic metabolic panel are within normal limits. Her initial high-sensitivity troponin is negative as is serum D-dimer.

An electrocardiogram (ECG) displays normal sinus rhythm with a left anterior fascicular block.  There are no acute ST- or T-wave changes and it is otherwise unremarkable and unchanged compared with her most recent ECG. Discussion with her cardiology group reveals that her last stress test or catheterization was several years ago. The cardiologist believed that because of her known CAD and the nature of her complaints, she should be admitted for serial troponins, ECG, and potential stress testing in the morning. 

Admitted to Hospital Telemetry Floor

The patient is admitted to the telemetry floor. The hospitalist physician associate (PA) wrote the admission orders, and the patient went to the unit at approximately 7 PM.

At approximately 10 PM, after her husband had left, the patient was noted to be restless. She began to get out of her bed and mumble. She was returned to her bed by her nurse, and she did so peacefully, but after a few minutes she would get out of her bed again. Attempts at redirection with conversation were met with incoherent verbal responses, but she was not aggressive. 

One-to-one supervision was initiated and the behavior continued. The hospitalist PA evaluated the patient for medical or pharmacologic causes of delirium and finding none, determined this to be a case of sundowning. After decreasing the light and sound in the room, as well as additional attempts at redirection, she was given a small dose of haloperidol. Eventually she became drowsy and slept through the night. In the morning, she appeared to return to her baseline cognitive function as reported by her husband, who had returned to the hospital.

Discussion

Sundowning, or sundown syndrome, is not a diagnosis but rather a characterization of neuropsychiatric symptoms that occur in the late afternoon, evening, or night.^1-4 This phenomenon has been most commonly described in older adults who have cognitive dysfunction/dementia or those who are institutionalized.^2-4 There are no specific or agreed-upon criteria for the phenomenon of sundowning, and the incidence is not well documented.^1-4 The most common symptoms associated with sundowning or sundown syndrome include but are not limited to agitation, aggression, anxiety, confusion, disorientation, restlessness, sleep disturbance, pacing, screaming, wandering, and yelling.^2-4 

These signs and symptoms are not specific to sundowning and are often seen with delirium.⁴ Generally, what is considered the distinguishing factor between sundowning and delirium is its temporal pattern and persistence.^2,3 Unlike delirium, sundowning occurs in and around the hours of twilight, and patients usually return to baseline in the morning hours.

The first description of sundowning was by D. Ewen Cameron, MD, in 1941, who at the time referred to the phenomenon as senile nocturnal delirium.^1-3,5 Dr Cameron outlined the occurrence as a pattern of nocturnal disturbance and delirium that “appears after retiring to sleep and clears up soon after getting up the next day.”⁵ It was thereafter described by multiple authors until the term “sundown syndrome” was coined by Lois K. Evans, PhD, RN, in 1987.^2,6 Evans recorded the symptomatology in a group of nursing home residents. Sundown syndrome was distinguished from delirium by its persistent nature.⁶ Subsequent reports of sundowning have noted a lack of consensus when describing the epidemiology and theorized etiology.^1,4

It is known that sundowning occurs in older adults with known dementia or cognitive dysfunction.^1,2,4 As such, a large portion of the literature related to sundowning is concentrated on patients with dementia.^2,4 Although the diagnosis of dementia is not requisite to sundowning, the severity of dementia has been correlated with the likelihood of sundowning across studies.^1-4 The presentation of sundowning may also be predictive of impending cognitive decline.² Although sundowning may be related to the presence of cognitive dysfunction, the pathophysiology is likely multifactorial, as not all patients with cognitive dysfunction and dementia display symptoms of nocturnal delirium.^2,4

Although theories of the pathophysiology are simply that, there are several known neurobiological, environmental, and pharmacologic factors associated with sundowning that have become the focus of research.¹ A predominance of the existing research suggests that most patients have evidence of alteration or disorder of circadian rhythm.^1-4,6,7 In particular, animal and human studies have linked disturbances in circadian rhythm and sleep-wake cycles to degeneration of the suprachiasmatic nucleus (SCN), which is part of the hypothalamus.^1-4 The SCN is considered the primary sleep-wake pacemaker of the human body, governing alertness during the day and sleep signaling at night.^1,3 Studies of aging and dementia demonstrate neuronal loss within the SCN as a physiologic component of aging.^3,4,8 Patients with Alzheimer dementia (AD) show comparatively increased volume loss and damage in the SCN, an increased incidence of sundowning, and altered sleep-wake cycles compared with healthy subjects.^2-4,8

Melatonin, which is produced and released by the pineal gland in response to darkness, specifically acts upon and is regulated by the SCN.^3,4,9-11 Mechanistically, melatonin binds receptors in the SCN, which in part suppress neuronal firing and stimulate phase shifting.¹⁰ Levels of melatonin have been shown to decrease with age and in patients with AD, and it has become a therapeutic target for many sleep disorders such as sundowning.^3,4,9,10 Thus, there is some agreement that an underlying mechanism of sundowning is degeneration of the SCN and decreased circulating melatonin. These changes are known to occur with age and dementia although causality cannot be definitively inferred. 

Other Contributing Factors

Other neurobiological changes that have been found in the sundowning population include impairment of the hypothalamic-pituitary-adrenal axis, cholinergic transmission, and altered serum cortisol levels.^2,4 Known environmental correlates include lack of adequate daily light exposure and daily routines, caregiver fatigue, and/or overstimulation such as noise during typical sleep times.^2-4 Many environmental factors have gotten attention, as they are also common to hospitalization and institutionalization. 

Medical and physiologic factors include mood disorder or disruption, pain, fatigue, or other unfulfilled physiologic needs.³ Pharmacologic factors may contribute and have been studied, although no definitive associations with a specific medication type or class have be found.^3,6 In particular, anticholinergics, antipsychotics, antidepressants, and hypnotics have been implicated as contributors.^2-4 Most of these have also been studied as treatment modalities for sundowning.⁴ Nevertheless, it is known that a “wearing-off” effect of some of these can cause delirium in susceptible patients and that many drugs have this potential in patients with dementia.^3,4 

Therefore, medications from the aforementioned classes and medications in general must be considered in older adults and/or those with cognitive decline presenting with sundowning. However, it is important to make the distinction that sundowning cannot be attributed to the effect of a singular medication or specific illness. That is, if a medication was precipitating the behavior and removed, subsequently extinguishing the symptoms, this would be delirium and not sundowning.  

Evaluation and Management

In the evaluation and management of sundowning, delirium is the primary differential diagnosis and must be ruled out.³ If the symptomatology is the direct effect of a medication or illness, the diagnosis is delirium. As noted, sundowning is described as a diverse group of neuropsychiatric symptoms occurring in the late afternoon or evening hours.^1,3,4 If a patient without a known history of sundowning presents in this way, a thorough history and physical to rule out modifiable causes must be obtained.⁴ This includes a head-to-toe examination to look for organic causes of infection, pain, or discomfort. 

History should assess changes in health and behavior from baseline before the event as well as current and new medications. History taking should also take into account that the primary population with sundowning includes those with cognitive decline and dementia. This population may not be able to adequately communicate discomfort in customary ways, and so multiple methods of gathering history may need to be employed.³ Medical history should assess whether an exacerbation of an existing illness, such as infection, cancer, an autoimmune disorder, etc. could be the precipitant. Serum laboratory and radiological evaluation should focus on common and patient-specific potential causes of delirium.⁴

Research and trials of pharmacologic and nonpharmacologic management options for management of sundowning are inconsistent.^1-3 Nonpharmacologic approaches such as behavior and environment modifications should be attempted prior to medications because responses to them in this population may be unpredictable.^3,4 

Light therapy is one of the more studied environmental interventions, and although methodologies vary, it entails increased light exposure in the afternoon and evening hours.^3,4 Many of the studies are small but have shown efficacy of light therapy in improving sleep-wake patterns, decreasing evening motor agitation.^3,4,7,11-13 However, a study specific to light therapy and sundowning has not been conducted.⁴ In Cochrane systematic reviews, the authors deemed the evidence for light therapy inadequate for sleep, cognition, and other neuropsychiatric behaviors in patients with dementia.^4,14-16 Other environmental and behavioral modifications have been employed with modest results. Environmental consistency, sensory and noise moderation, avoiding evening stimulation, sleep-wake schedule adherence, caregiver education, and even music and aroma therapies may ameliorate sundowning symptoms in some patients.^3,4,17

Medication Management

The pharmacokinetics of the aging and dementia population is unique and must be considered with pharmacologic management of sundowning. Likewise, these patients are often on multiple medications, which can reduce or influence efficacy and precipitate adverse interactions. The medication classes most studied for the treatment of sundowning have been chosen based upon its hypothesized etiology.² These include melatonin, acetylcholinesterase inhibitors, and antipsychotics.^3,4 The body of evidence on the use of melatonin in sundowning is pejoratively inconclusive.^2-4,7 However, some studies show improvement of subjective and objective metrics of sleep and nighttime neuropsychiatric symptoms.^4,18,19

Cholinesterase inhibitors have been a mainstay of treatment of some dementias and have been shown to decrease behavioral and psychological symptoms, particularly with AD.^3,20 Case evidence suggested some utility with the use of the cholinesterase inhibitor donepezil in sundowning in Lewy body dementia.^3,7,21 Galantamine and rivastigmine also have been studied for neuropsychiatric symptoms of dementia, with some success but not specifically for sundowning.³ There are no specific recommendations for their use.³ 

Similarly, antipsychotics are commonly used in the dementia population to manage psychosis and agitation.^3,4,11,22 They are also often used to manage acute sundowning symptoms. There is evidence of the typical and atypical antipsychotics for the chronic management of neuropsychiatric symptoms in dementia, but their use specifically for sundowning is predominantly anecdotal.^3,4 Many of the antipsychotics will produce a dose-dependent somnolence and may be effective in the promotion of sleep in both acute presentations and chronic settings.³ As with all medications in this population, patient medical history, clinical context, and current medications must be considered when treating sundowning pharmacologically.³

Conclusion

Sundowning has not been defined in the literature as a disease process but is often hypothesized as a manifestation of existing neurologic dysfunction. Although the etiology is unknown, sundowning appears to be comorbid with circadian dysfunction, and it is seen disproportionately in patients with cognitive decline and dementia. The evaluation of it must take care to rule out infectious, inflammatory, pharmacologic, and other organic causes of delirium. Sundowning is often treated with melatonin, cholinesterase inhibitors, and antipsychotics. Although these and other treatment modalities have shown some efficacy, their use is empirical based on mechanism of action and the concurrent treatment of the symptomatology common to dementia.

Patients who develop symptoms of sundowning while inpatient, most often revert to baseline upon returning home.  The 80-year-old woman with chest pain was discharged to home with her husband after an inpatient cardiology evaluation. No additional instructions were given related to her sundowning symptoms.  While potentially a predictor of cognitive decline, it is unlikely that her symptoms will recur upon returning to the home environment.  For patients with cognitive dysfunction who have sundowning symptoms at home, environmental interventions such as afternoon light exposure, maintenance of routines and creating tranquil sleeping conditions are the first-line recommendations. Patients with more advanced disease may require in-home care/support as they can be extremely challenging for caregivers.  

This article originally appeared on Clinical Advisor