Sundowning syndrome in Alzheimer's disease: etiology and treatment approaches

Sundowning Syndrome: Etiology and Treatment

An escalation in disruptive behaviors in the late afternoon and early evening among institutionalized patients suffering from dementia and Alzheimer's disease has been a recognized phenomenon for over 60 years (Bachman & Rabins, 2006). The timing of the onset of disruptive behaviors has led to calling this phenomenon sundowning, sundowning syndrome, and nocturnal delirium. Symptoms traditionally associated with sundowning include increased motor activity, confusion, yelling, aggression, wandering, agitation, and anxiety (Scarmeas et al., 2007). In spite of this long history, and a general consensus among clinicians and medical textbooks that sundowning is real, there is still a substantial amount of controversy among researchers whether it's more illusion than fact.

The controversy is due in part to the lack of a consensus definition for sundowning. Cohen-Mansfield (2007) cites three different definitions in order to highlight this lack of consensus: (1) "a syndrome of recurring confusion and increasing levels of agitation, which coincide with the onset of late afternoon and early evening," (2) "the onset or exacerbation of delirium during the evening or night, with improvement or disappearance of delirium during the day," and (3) "an exacerbation or appearance of symptoms indicating increased arousal or impairment in late afternoon, evening or at night among elderly, demented individuals" (p. 396). These definitions reveal some of the discrepancies that continue to plague this area of research, including whether to include nighttime episodes, which symptoms fit under sundowning, and whether dementia is a prerequisite. These conceptual differences manifest themselves in various ways as sundowning research progresses, thus prolonging the controversy (Bachman & Rabins, 2006).

In an attempt to create a more solid foundation for future sundowning studies, a group of researchers from multiple institutions conducted a large Alzheimer's follow-up study spanning a 20-year period (Scarmeas et al., 2007). Of the almost 500 patients in the study, approximately 50% exhibited the symptoms of sundowning at some point during the course of the disease. This represented 60% of all patients who engaged in disruptive behavior during the study period. The likelihood that patients would exhibit disruptive behavior during any time of the day increased 7% (p < 0.001) for each year they suffered from the disease. When adjusted for an array of confounders, sundowning was a significant predictor of cognitive decline, but not mortality, institutionalization, or functional decline. Sundowning, as defined by this study, therefore afflicts 50% of all Alzheimer's patients at during the course of their disease.

Sundowning Etiology

There are many theories that attempt to explain the cause of sundowning syndrome, including both psychological and physical. The psychological theories include exacerbated feelings of social isolation or a nonspecific unmet need (Bachman & Rabins, 2006). On the physical side there has been considerable attention paid to the possible role of circadian rhythms and the main circadian clock, the suprachaismatic nucleus (SCN). Patients with early stages of dementia or Alzheimer's frequently have fragmented sleep-wake cycles that are defined by nocturnal awakenings and daytime naps, and when SCNs from Alzheimer patients were examined post-mortem, signs of pathology were evident (reviewed in: Volicer, Harper, Manning, Goldstein, & Satlin, 2001).

Evidence supporting the role of SCN pathology in sundowning was revealed by a study examining shifts in the daily peaks of core body temperature and motor activity, both accepted markers for circadian rhythm (Volicer et al., 2001). The Alzheimer's patients were divided into three groups for the purpose of the study; patients who engaged in sundowning behavior frequently, sometimes, or rarely. A control group was also included that consisted of elderly patients with no evidence of neurological or psychiatric disease. Patients who engaged in sundowning behaviors frequently reached their peak core temperature an average of 3 hours later than the controls and 2 hours later than the other Alzheimer's patients. The peak in motor activity was reached 3-1/2 hours later for patients who rarely or sometimes engaged in sundowning behavior, and 5-1/2 hours later for patients who frequently engaged in this behavior. The daily peaks in motor activity and core temperature were significantly less correlated in frequent sundowning patients, and the amplitude of the daily fluctuations in these markers was also reduced. These results provide an explanation for the late afternoon and early evening timing of sundowning behavior and highlight the importance of a tightly regulated circadian clock in preventing their occurrence.

The post-mortem SCN pathology that was observed in Alzheimer's patients involved a significant reduction in neuronal populations, including those responsible for producing vasopressin and vasoactive intestinal polypeptide (reviewed in: Sterniczuk, Dyck, LaFerla, & Antle, 2010). Damage to the optic nerve and retinal ganglion cells were also observed post-mortem, a condition which would have restricted the ability of the SCN to accurately gauge the time of day. In mice genetically-engineered to develop an Alzheimer's-like phenotype, the SCNs were found to have significantly fewer vasopressin- and vasoactive intestinal polypeptide-producing neurons when compared to controls. In addition, the sleep/wake cycle became fragmented in these mice during early stages of the disease phenotype, resulting in increased activity during the sleep period and decreased activity during the active period. This circadian phenotype developed in the absence of optic nerve or retinal ganglion cell degeneration, suggesting SCN neuronal atrophy, rather than a loss of accurate light/dark information, underlies at least part of the sundowning behavior in Alzheimer's patients.

Activity Therapy

Expanding further on the theme of resetting the biological clocks of Alzheimer's patients to reduce sundowning behavior, Vance and Cohen (2004) suggest combining light therapy with structured activities designed to reinforce a well-defined sleep/wake cycle. This can include limiting daytime napping, dimming the lights in rooms during the evening to promote melatonin production in anticipation of sleep, engaging in physical activities when possible, and combining light therapy with activities designed to engage patients for a period sufficient to reset their biological clocks.

1. Bachman, D. & Rabins, P. (2006). Sundowning and other temporally associated agitation states in dementia patients. Annual Review of Medicine, 57, 499-511

2. Cohen-Mansfield, J. (2007). Temporal patterns of agitation in dementia. American Journal of Psychiatry, 15, 395-405

3. Volicer, L., Harper, D.G., Manning, B.C., Goldstein, R., & Satlin, A. (2001). Sundowning and circadian rhythms in Alzheimer's disease. American Journal of Psychiatry, 158, 704-711

4. Sterniczuk, R., Dyck, R.H., LaFerla, F.M., & Antle, M.C. (2010). Characterization of the 3 xTg-AD mouse model of Alzheimer's disease: Part 1. Circadian changes. Brain Research, 1348, 139-148

5. Scarmeas, N., Brandt, J., Blacker, D., Albert, M., Hadjigeorgiou, G., Dubois, B., . . . Stern, Y. (2007). Disruptive behavior as a predictor in Alzheimer's disease. Archives of Neurology, 64, 1755-1761

6. Vance, D.E. & Cowan, R.N. (2004). Activity therapy as a vehicle for resetting the biological rhythm in adults with Alzheimer's disease. Activities, Adaptation & Aging, 28, 1-16