Effects of Low-Frequency Cranial Electrostimulation on the Rest-Activity Rhythm and Salivary Cortisol in Alzheimer's Disease [Abstract]

Scherder, E., Knol, D., van Someren, E., Deijen, J-B, Binnekade, R., Tilders, F. and Sergeant, J. Neurorehabilitation and Neural Repair, 17(2):101-108, 2003.

Authors’ Abstract: Objective. In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD). Method. It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes. Results. Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol. Conclusions: These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed.

Reviewers Note: While this small pilot study appears to indicate that CES is not effective in Alzheimer's disease, there were significant problems with the protocol and data analyses. First, a trial treatment was applied to both the experimental and control groups. Previous experience with CES research shows that cross-overs from treated to untreated groups are not possible with CES because even a little treatment can produce long-term effects and no successful washout period has ever been established for CES. From the write-up, it is unclear if the current was applied and then turned off for the control group, which again, would potentially provide treatment, or exacerbate disorientation due to partial treatment effects. Salivary cortisol measurements were taken at irregular times causing the primary dependent variable to be invalid when used to compare results. The authors attempted to compensate for this through statistical modeling using dummy variables and by obtaining the maximum cortisol level by extrapolating it from the available data and using estimates as actual data. This study found cortisol levels increased in both the treatment and placebo treatment groups raising a question of validity about salivary cortisol testing and/or storage of the samples. Additional research is needed to determine if CES, a proven treatment for anxiety and depression, might be of use in Alzheimer's patients.

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