Sundown syndrome (SS) is a well-known phenomenon for professionals that work with patients with dementia and for their relatives or caregivers, but nevertheless there is not a unique definition that suits the results of the few studies about it. There is usually a consensus in considering SS as the onset or exacerbation of neuropsychiatric symptoms in the late afternoon or the early evening (Canevelli et al. 2016).
Clinical and Epidemiological Features
Despite lacking a universal definition of SS, it is accepted that it comprises behavioral and neuropsychiatric manifestations as agitation, disorientation, confusion, psychomotor restlessness, anxiety, aggressiveness, screams, wandering, and hallucinations. Though being a frequent entity, SS has not received great clinical and scientific attention yet, as demonstrated by the scarce studies and their controverted results. For example, available research about SS prevalence in dementia patients reports rates ranging between 2.4% and 66% (Bliwise 2000; Khachiyants et al. 2011), becoming a relevant problem to face in institutionalized older people. In fact, it was found to be the second most common type of behavioral problem in dementia patients (See “Behavioral and psychological symptoms of dementia”). It has also been reported that up to a 20% of patients with Alzheimer disease (AD) can show SS at some moment during the illness, and although it can appear in other non-AD dementias such as Lewy body dementia or vascular dementias, there is not enough epidemiological research to specify prevalences in each of them (Canevelli et al. 2016). Nevertheless, it should be taken into account that in clinical practice, this phenomenon is more associated with dementia stage or severity of the cognitive impairment than with the type of neurodegenerative syndrome.
Advancing in the study of SS is essential considering the great impact it has on patients and their caregivers and the society too. Presence of sundowning represents an economical burden as reflected in a higher number of hospitalizations and a longer duration of hospital stays. It is also considered a cause of caregiver stress (See “Caregivers’ stress”), and thereby it is related to the decision of institutionalizing the patient. It is also relevant to understand that SS appears in a time of the day when the caregiver can be more fatigued. Stress and fatigue could lead to the employment of less efficient strategies for the management of the SS, worsening it in a vicious circle way (de Vugt et al. 2004). Furthermore, caregivers can suffer from sleep and emotional disturbances. Living with a dementia patient who suffers SS means that the person wakes up several times during the night, wanders around the house, and even shouts or shows other disruptive behaviors. Accordingly, caregivers’ quality of sleep is usually diminished, and in this condition it is not rare to find anxiety and depressive symptoms in them (Mahoney et al. 2005; Cipriani et al. 2015).
Patients experiencing SS can also suffer negative consequences. Their quality of life can be reduced, their own safety may be compromised, and they can receive uncomfortable treatments such as physical restrictions (Cipriani et al. 2015). Different studies have proposed that sundowning could represent a marker of frailty in the dementia patient, thus predicting a faster decline of cognitive and functional levels (Scarmeas et al. 2007; Ferrazzoli et al. 2013).
All the above highlights the importance of a better understanding of SS and an increasing of researches about it.
Assessment and Diagnosis
Given the heterogeneity in its clinical symptoms and in the moment of the day when SS is supposed to start, no standardized diagnostic criteria have been defined yet. The diagnosis keeps being fundamentally clinical and based in a careful medical history and observation of the patient when it is possible.
Assessment of sundowning should be multidimensional following the characteristics of this phenomenon. SS is easily identified through patient observation and also can be deducted from caregiver’s reports both in familiar and institutional settings. In addition, it should be noted that clinicians still lack specific validated assessment tools (scales, interviews, etc.) and there is no laboratory test either that helps to lead to a definitive diagnosis.
In this circumstance it is relevant to elaborate an exhaustive medical history of the patient followed by a physical exploration. Some factors have been proposed in relation to SS appearance. Relative to the patient’s health status, variables like pain, sensory problems, sleep disorders, or emotional disturbance have shown relationship with the emerging and worsening of SS and should be explored in detail. Moreover, side effects of some medications should be considered as well as the presence of other conditions that can exhibit behavioral disturbances, for example, cerebrovascular events, metabolic disorders, or systemic infections, to help in the differential diagnosis with entities like confusional syndrome (Canevelli et al. 2016). Other circumstances as urine smell, frequent awakenings along the evening, a shorter time since admission to the facility, residence in the current room for less than 1 month, and higher levels of confusion during the evening have been pointed as relevant (Evans 1987; Bachman and Rabins 2006).
Authors also list a set of environmental factors that could act as precipitants of this phenomenon, including light exposition during the day, presence of noise or other types of overstimulation, and availability of caregivers late in the afternoon or early evening (Canevelli et al. 2016). Addressing these questions is relevant because some of them are treatable problems that sometimes require caregiver education, simple changes in medication prescriptions or in the patient’s routine.
Some efforts have been done trying to better identify possible candidates to show SS among dementia patients (See “Dementia”). In this sense it could be helpful to have a characteristic clinical profile of these subjects. Available data in this direction is still scarce, but results show that age, Reisberg’s Global Deterioration Scale (GDS) score, and the presence of insomnia or parasomnia independently defined the presence of SS with a predictive capacity of 80.1% (Angulo et al. 2018).
Key Research Findings
Although there is growing scientific evidence on the biological basis of SS, research is still scarce, and results sometimes show inconsistences. However, a summary of the most relevant findings is reviewed below.
A large part of the studies on the pathophysiology of sundowning has been focused on the disturbances of the circadian rhythm, which is responsible for the regulation of sleep-wake cycle and promotes nocturnal sleep. Generally, circadian alterations have been associated with the dysfunction of the suprachiasmatic nucleus, located in the hypothalamus. A relationship has been described between the loss of volume in the suprachiasmatic nucleus and age, gender, and neurodegenerative syndromes such as AD (See “Alzheimer’s Disease”), and in this line, it has been found that patients with severe AD showed significant neuronal loss and neurofibrillary tangles in the suprachiasmatic nucleus (Swaab et al. 1985; Stopa et al. 1999).
After receiving sensorial information from the retina through the retinohypothalamic tract, suprachiasmatic nucleus has efferent pathways toward other nuclei in the hypothalamus and to the pineal gland, thus influencing melatonin levels (a hormone secreted in response to darkness). Different studies have found a reduction in melatonin levels in healthy aging. However, a systematic review showed that while 24-h melatonin production seems not to change, maximal nocturnal peak concentrations might do so in people aged over 65 years (Scholtens et al. 2016). Other data in AD patients suggest that there are lower melatonin levels compared to controls, even in preclinical stages of the disease (Srinivasan et al. 2006).
Another line of research has been centered in the cholinergic system, since it is known that it sends projections toward the suprachiasmatic nucleus (Canevelli et al. 2016). Impairment in this system has been considered as a possible mechanism underlying SS.
On the other hand, another research found higher cortisol levels in AD patients presenting sundowning, thereby hypothesizing that a dysfunction in the hypothalamic-pituitary-adrenal axis could be related to SS in AD (Venturelli et al. 2013).
Although findings are not still clear about SS causes, there are enough data to propose different treatments, both pharmacological and non-pharmacological, with the aim of improving symptoms and quality of life of patients and caregivers.
Pharmacological options have included melatonin supplements, cholinesterase inhibitors, and antipsychotics. Taking into account that SS is considered as an alteration of circadian rhythm, it makes sense to try to approach its symptoms with melatonin. Treatment with melatonin in dementia patients seems to be effective in improving sleep, increasing total time of sleep and also its efficiency, but with no effects on patients’ cognition (Xu et al. 2015). A few randomized controlled studies achieve inconsistent results. One of the studies found that melatonin supplements did not improve sleep and agitation in AD institutionalized patients when comparing with placebo (Gehrman et al. 2009), while other studies showed an improvement of these symptoms after doses ranging from 2.5 to 10 mg daily (Asayama et al. 2003; Singer et al. 2003). Moreover, one of the advantages of melatonin is that it has been related to the absence of secondary effects (Xu et al. 2015).
In AD treatment, cholinesterase inhibitors are widely used, as well as in other dementia syndromes. It has also been proposed that circadian disorders can be related to less cholinergic activity, so some studies have analyzed the effect of these medicines on SS of patients suffering AD or other dementias. Nevertheless, results are scarce and not enlightening. In some cases treatment with donepezil produced sleep disorders and insomnia, while in other cases SS improved. Some authors have suggested that, in these cases, improvement of SS could be due to a better cognitive functioning after donepezil use (Cipriani et al. 2015).
Another type of medication frequently used in clinical practice for treating sundowning are antipsychotics, usually atypical ones, at the minimum effective dose (low doses) and 30 min before the time SS normally appears. Anyhow, its use should be individualized only when symptomatology impacts on patient or caregiver’s well-being.
Finally, the use of benzodiazepines is not recommended for this kind of chronic behavior disorder in dementia as it raises the risk of confusional syndrome, falls, and other side effects.
Other studies are oriented to improve SS using non-pharmacological approaches. In fact, some authors affirm that this kind of therapies should be primarily used in sundowning treatment. Some environmental modifications seem to be useful. Among them, light therapy is the most used in clinical practice. It consists of increasing light exposure during late afternoon and evening hours, and research has shown it can help reducing SS episodes and motor restless behaviors in people with dementia (Satlin et al. 1992; Haffmans et al. 2001). Thus, some studies recommend 30 min of 10.000 lux light exposure in these patients, arguing that it is easily adjustable to the routine of the institutions or centers (Staedt and Stoppe 2005).
Apart from light exposure, there are other recommendations to reduce SS. These include reducing environmental noise (staff’s or visitors’ conversations, banging of dishes, etc.), facilitating daily routines (guaranteeing enough physical activity during light hours and specially outdoors, for example, walking with caregivers), decreasing sensorial stimulation during the evening (television time, high music, etc.), or avoiding afternoon nappings (Canevelli et al. 2016; Staedt and Stoppe 2005; Shih et al. 2017). Other proposals refer to music therapy (Van Der Steen et al. 2018), aromatherapy (Nguyen and Paton 2008), or caregiver education (Javadpour et al. 2009). Although there is still no great scientific evidence of their effectiveness, they seem to be useful in clinical practice.
Future Directions of Research
Sundowning is a complex behavioral disorder which at present is not fully understood; hence different future directions have been recommended by scientists and clinicians. In general it is assumed that new research should be targeted to a better recognition and diagnosis of the symptoms, what would lead to a higher well-being of both patients and caregivers. In this sense, three broad research lines can be drawn.
First big line of study refers to SS etiology. From a pathophysiological point of view, it seems to be relevant to clarify sundowning basis, thus deepening the analysis of melatonin, cholinergic system, and cortisol roles. Another possibility already suggested is centered in the relationship of SS with neuronal energy loss and the role of oxidative stress, as it has been argued that this kind of stress could be associated with senile plaque formation and degeneration of suprachiasmatic nucleus, altering circadian rhythms and favoring SS appearance. Furthermore, in a similar way, inflammatory stress mediated by cytokines seems to be important too. Some data showed that mild chronic stress could provoke brain changes in brain structures as the hippocampus, critical for cognition and emotion, linking inflammatory stress to neurodegenerative disorders (Gnanasekaran 2016). This could give scientists a reason to analyze its relation to sundowning too.
Second general line of research is about assessment of SS. Specific validated instruments of assessment of SS need to be developed to facilitate daily clinical practice and diagnosis of this phenomenon. Studies could also focus on the identification of clinical risk profiles in order to prevent, if possible, the onset of SS or to make a better follow-up of future candidates for it.
The third and last investigation arm needs to guide efforts toward treatment approaches in SS. More randomized controlled studies are needed to improve the statistical power of findings about the effects of therapies. This would lead to the development of better interventions in pharmacological, behavioral, and environmental ways to improve symptoms and promote better health care and services for patients and caregivers.
Sundown syndrome is a complex phenomenon usually described as the onset or exacerbation of neuropsychiatric symptoms in the late afternoon or the early evening. It is frequently seen in dementia patients, specially in severe stages, and among its features are agitation, disorientation, psychomotor restlessness, anxiety, aggressiveness, and other behaviors. It represents an important burden for caregivers and society and reduces patient’s quality of life.
Research is still insufficient to determine SS etiology though there are different proposals centered in the disruption of circadian rhythms, altered melatonin levels, or the role of the cholinergic system in addition to other environmental factors and circumstances related to patient’s health. Nevertheless, no standard criteria have been defined yet and the diagnosis is still clinical, based on a medical history and a careful observation of the patient.
Treating sundowning continues representing a challenge for clinicians. Studies, though scarce, suggest melatonin supplements, cholinesterase inhibitors, and atypical antipsychotics as useful from a pharmacological point of view. Other non-pharmacological approaches are light therapy, environmental modifications, and caregiver education to promote behavior changes and better routines for the patient.
Considering the above, more efforts are needed to shed light on sundowning with the aim of improving the attention given to patients and their families.
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