Response to: Arendash GW et al. (2010) J Alzheimers Dis 19, 191-210

1 March 2010

A very interesting article by Arendash et al. (1) was published in the January 2010 issue of Journal of Alzheimer’s Disease. The results suggested that exposure to radiofrequency (RF) radiation similar to that emitted by mobile phones may  provide cognitive benefits both in normal mice and  in a transgenic mouse model of Alzheimer’s disease (AD).

In the Introduction, the authors state “To date, no controlled long-term studies of high frequency /cell phone EMF effects on cognitive function have been done in humans, mice, or animal models for AD.” Although the sentence is very true as it is (because rats are not specifically mentioned), another sentence in the Abstract – “this report presents the first evidence that long-term EMF exposure directly associated with cell phone use…provides cognitive benefits” – is certainly not true. In a paper published two years earlier (2), we reported improved learning and memory in water maze tests in young male Wistar rats exposed to a mobile phone RF signal for  5 weeks.

The electromagnetic field exposures in the two studies were similar though not identical: Arendash et al. exposed the animals to a 918 MHz electromagnetic field for 2 h/day at a (reported) exposure level of 0.25 W/kg for 2 h/day, whereas we used a 900 MHz field for 2 h/day at 0.3 or 3 W/kg. However, there are also some differences. We used a pulse-modulated signal similar to that emitted by GSM mobile phones, whereas Arendash et al. probably used a continuous signal (no modulation is reported in the paper).  The most important difference in the results is that we found improved learning and memory already after 5 weeks of exposure, while Arendash et al. reported no beneficial effects before 5 months of exposure. It remains to be investigated whether this difference is related to differences in exposure level; a shorter exposure time might be sufficient to cause effects at higher exposure level. We found some evidence of a dose-response relationship - improved task acquisition was found in both exposed groups, but improved memory retention was observed only in the higher exposure group. Of course, differences in results may also be related to the fact that animal models and testing methods were not identical in the two studies.

A major weakness in the article of Arendash et al. is insufficient characterization of the electromagnetic field exposure system and dosimetry.  The description of the exposure system is very brief and, most importantly, there is no information on how the specific absorption rate (SAR, the “dose” of RF radiation) was determined. The physics of RF electromagnetic fields is very complex, and exposing animals to a well-defined “dose” is much more difficult than giving a dose of a chemical. Adequate reporting of the dosimetry is therefore essential in any study reporting biological effects of RF radiation. The complexity of the issue is well illustrated in the paper (3) that reports the technical details and dosimetry of the exposure system used in our rat study. Arendash et al. reported surprisingly large increase of body temperature (over 1°C) in the exposed animals during 1-hour exposure periods. The reported SAR level of 0.25 W/kg is so low that it should not result in measurable increase of body temperature, which raises doubts that the true SAR may have been higher than was reported. The authors’ interpretation was that the temperature increase (seen during 1-h exposure of animals that had been exposed for 8 months) was not a result of direct heating, and they presented data showing that single acute exposures did not increase brain temperature. However, the temperature data from the acute and long-term studies are not directly comparable, as the measurement methods were different (rectal vs. temporal muscle probe). That the temperature measurements (both with the rectal probe and the temporal muscle probe) were performed during electromagnetic field exposure introduces additional problems for the interpretation of the temperature data:  the electromagnetic field may have coupled directly into the probes (which can act as antennas) and the resulting interference may have biased the readings up or down. 

Inadequate dosimetry does not totally invalidate the results of Arendash et al. The “medicine” is promising although the dose used in the trial is not known. Given that positive effects on cognitive function are supported by two independent experimental studies and recent epidemiological findings (4), it is easy to concur with the conclusions of Arendash et al. that these surprising findings justify RF electromagnetic field exposure “as a non-invasive, non-pharmacologic approach worthy of vigorous investigation”. Like in the case of pharmacological agents, it is important to investigate the dose-response relationship, so any further experimental studies should include proper reporting of dosimetry and preferably more than one exposure level.

Timo Kumlin and Jukka Juutilainen
University of Eastern Finland
Department of Environmental Science
P.O.Box 1627, FI-70211 Kuopio
Finland

Heikki Tanila
University of Eastern Finland
A.I.Virtanen Institute for Molecular Sciences
Kuopio, Finland

Lauri Puranen
STUK- Radiation and Nuclear Safety Authority
Helsinki, Finland

References:
1. Arendash GW, Sanchez-Ramos J, Mori T, Mamcarz M, Lin X, Runfeldt M, Wang L, Zhang G, Sava V, Tan J, Cao C. Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer's disease mice. J Alzheimers Dis. 2010 Jan;19(1):191-210.
2. Kumlin T, Iivonen H, Miettinen P, Juvonen A, van Groen T, Puranen L, Pitkäaho R, Juutilainen J, Tanila H. Mobile phone radiation and the developing brain: behavioral and morphological effects in juvenile rats. Radiat Res. 2007 Oct;168(4):471-9
3. Puranen L, Toivo T, Toivonen T, Pitkäaho R, Turunen A, Sihvonen AP, Jokela K, Heikkinen P, Kumlin T, Juutilainen J. Space efficient system for whole-body exposure of unrestrained rats to 900 MHz electromagnetic fields. Bioelectromagnetics. 2009 Feb;30(2):120-8.
4. Schüz J, Waldemar G, Olsen JH, Johansen C. Risks for central nervous system diseases among mobile phone subscribers: a Danish retrospective cohort study. PLoS One. 2009;4(2):e4389.