A New Perspective on Agitation in Alzheimer's Disease: A Potential Paradigm Shift

Agitation is a common and difficult-to-manage neuropsychiatric syndrome in dementia. Recently, an association with the autonomous nervous system has been suggested. From the literature researched, however, only two studies investigating autonomic function concomitant to agitation situations appeared; one case series comprised two American veterans with vascular and Alzheimer's dementia, respectively, and in a case series of patients with CLN3 (juvenile neuronal ceroid lipofuscinosis), this was found to be the most common neurodegenerative disease leading to dementia in childhood. In both case series, the measurement of the autonomic system disclosed a parasympathetic withdrawal and sympathetic hyperactivity in the temporal context with agitated behavior. If the time-wise-related autonomic imbalance shown previously can be demonstrated in a larger cohort of patients with Alzheimer's disease, the use of transcutaneous vagal stimulation might be a potential paradigm shift in the treatment of agitation in Alzheimer's disease.