Rest-activity rhythm disruption is a prominent clinical feature of Alzheimer's disease (AD). The origin of the altered rest-activity rhythm is believed to be degeneration of the suprachiasmatic nucleus (SCN). In accordance with the 'use it or lose it' hypothesis of Swaab [Neurobiol Aging 1991, 12: 317-324] stimulation of the SCN may prevent age-related loss of neurons and might reactivate nerve cells that are inactive but not lost. Previous studies with relatively small sample sizes have demonstrated positive effects of peripheral electrical nerve stimulation on the rest-activity rhythm in AD patients. The present randomized, placebo-controlled, parallel-group study was meant to replicate prior findings of electrical stimulation in AD in a substantially larger group of AD patients. The experimental group (n = 31) received peripheral electrical nerve stimulation and the placebo group (n = 31) received sham stimulation. Effects of the intervention on the rest-activity rhythm were assessed by using wrist-worn actigraphs. Near-significant findings on the rest-activity rhythm partially support the hypothesis that neuronal stimulation enhances the rest-activity rhythm in AD patients. Interestingly, post-hoc analyses revealed significant treatment effects in a group of patients who were not using acetylcholinesterase inhibitors concomitantly. We conclude that more research is needed before firm general conclusions about the effectiveness of electrical stimulation as a symptomatic treatment in AD can be drawn. In addition, the present post-hoc findings indicate that future studies on non-pharmacological interventions should take medication use into account. © 2006 European Sleep Research Society.