Association between altered systemic inflammatory interleukin-1β and natural killer cell activity and subsequently agitation in patients with Alzheimer disease

Objective: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. Methods: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1 beta (IL-1 beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). Results: Elevations in night behavior and blood cortisol, IL-1 beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1 beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. Conclusions: The increased IL-1 beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD. Copyright (C) 2009 John Wiley & Sons, Ltd.