Thursday June 24 2010
In Alzheimer's, abnormal protein tangles (red) form in brain cells
“Applying magnets to the brains of Alzheimer's disease sufferers helps them understand what is said to them”, The Independent has claimed.
The news is based on a small trial of an experimental magnetic therapy called rTMS, which some believe can reorganise brain cells and improve neurological functions.
Over four weeks, five patients were given rTMS and five were given two weeks of sham treatment followed by two weeks of real rTMS. The rTMS was applied to the area of the brain known to be involved in speech and communication, which are often impaired during Alzheimer’s disease. After two weeks, those treated solely with rTMS showed improvements in sentence comprehension. Those receiving the sham treatment did not improve. The sham group then improved a similar amount after two weeks of real rTMS.
Unfortunately, the technique did not improve other important language abilities, such as talking, cognitive function or memory. Equally, the design of this small study means that it cannot inform us about the long-term effects or potential harms from rTMS. While the use of rTMS in dementia will be of interest to neuroscientists, it should be seen as an experimental technique until larger, longer-term studies can evaluate it further.
Where did the story come from?
The study was carried out by researchers from the IRCCS Centro San Giovanni di Dio Fatebenefratelli and other educational and research institutes in Italy. This research was supported by a project grant from the Italian Ministry of Health and the Associazione Fatebenefratelli per la Ricerca (AFaR) research foundation. It was published in the peer-reviewed Journal of Neurology, Neurosurgery & Psychiatry.
The other papers reporting this study, including The Daily Telegraph, have fairly represented the preliminary nature of this experimental research, and highlighted the fact that only 10 patients were treated. Some newspaper headlines and the scientists’ press release probably overstate the case presented by this small study by suggesting that the treatment “holds considerable promise”.
What kind of research was this?
This was a randomised controlled trial in which 10 patients with moderately severe Alzheimer disease (AD) were randomly assigned to receive either a course of magnetic stimulation therapy or a placebo treatment and then a shorter course of magnetic stimulation.
The researchers have proposed that the treatment, called repetitive transcranial magnetic stimulation (rTMS), may be a way to improve the symptoms of people with AD. While the experimental therapy has not been widely studied, some believe that it has the potential to stimulate the brain cells so that they reorganise themselves and improve cognitive functions. The researchers were particularly interested in how the therapy might affect thinking, memory and language in the long term when stimulation was applied to the left dorsolateral prefrontal cortex, an area of the brain known to be involved in speech.
The treatment-only group had a four-week course of genuine rTMS treatment. The second group had a two week placebo treatment, followed by two weeks of real rTMS stimulation. Sessions took place once a day for five days a week.
The main limitations of this study are its small size and its inability to determine whether the effect is temporary. As the placebo group in the trial only received the placebo for a short period of time, it is difficult to say how much of the improvement seen was due to natural variation in the ability to complete comprehension tests.
What did the research involve?
The researchers randomly assigned patients to two groups:
- A real rTMS group, in which the patients received four weeks of rTMS stimulation to the language region of the brain
- A placebo then real rTMS group, in which patients received placebo stimulation to the language region of the brain for the first two weeks, followed by a two-week course of real stimulation
Each week of rTMS treatment consisted of 25-min sessions on five days. The dose used was the same dose required to stimulate a movement when applied to the motor part of the brain for each participant. A two-second burst of rTMS was delivered, followed by 28 seconds of no stimulation. A total of 2,000 pulses were delivered in each session.
It is likely that patients were aware of when they were receiving active treatment, although the researchers doing the testing did not know to which group the patients were allocated.
Patient performance before and after treatment was assessed by using screening tests for dementia. They assessed memory, executive functions and language, and were conducted before the start of the study and at two, four and 12 weeks. The 12-week assessment was given eight weeks after the last treatment.
All the tests were administered and scored according to standard procedures. They were analysed using a standard statistical technique called analysis of variance.
What were the basic results?
Both groups of five patients were similar in terms of dementia scores, with each scoring about 66% on the sentence comprehension test.
After two weeks of the trial, the four-week rTMS treatment group improved their performance on the sentence comprehension test, scoring 77%. The other group did not improve their performance. However, the two groups showed no difference in other outcomes, such as cognitive tests, at two weeks.
A significant improvement was found in both groups after their active treatment sessions. At four weeks, the group treated for four weeks improved to 77.3% and the group that was given two weeks of real rTMS treatment improved to 75.4%.
At 12 weeks (eight weeks after treatment stopped) both groups had sustained a similar improvement (78.7% and 75.7%).
How did the researchers interpret the results?
The researchers say that their findings provide initial evidence for the persistent beneficial effects of rTMS on sentence comprehension in AD patients. They hope that, along with other treatments, this may represent a new way of treating language dysfunction in AD patients.
Having said that, the results are preliminary and signify potential uses of stimulating the brain with magnetic forces. They go on to to justify the research by claiming that it “holds considerable promise, not only for advancing our understanding of brain plasticity mechanisms, but also for designing new rehabilitation strategies in patients with neurodegenerative disease”.
This is a very small study, which has shown a short-term effect of an experimental technique that delivers repetitive strong magnetic fields to the brain. There are several technical points to note about the study, and some points about its applicability for general use:
- The random allocation to two groups was not described in the report, meaning it is not clear how this was done. Studies with small numbers like this are particularly prone to bias due to the imbalance between the groups in their baseline characteristics. The characteristics of the groups were reported by the researchers and appeared to be similar, although the real rTMS group did have slightly higher education levels (6.4 years compared to 4.8 years in the placebo group).
- The fact that no group received a full four-week placebo treatment means that it is not possible to compare the effects of four weeks of treatment against a group that was not treated at all. It would be interesting if the effect of the treatment wore off and, if so, how long it would take for all patients to return to the baseline level of language understanding. The researchers could have done this, but did not.
- The applicability of this treatment to all patients with Alzheimer’s disease is not at all clear. Maintaining overall function for as long as possible is important to people with Alzheimer’s disease, but these sorts of outcomes were not measured or did not improve.
- Many of the tests that the researchers used to assess things such as the ability to name objects (a specific problem for people with Alzheimer’s disease) did not improve. The large number of statistical tests performed increases the likelihood of observing statistically significant differences just by chance.
These researchers have identified some short-term benefits in some people from their new treatment: however, before the headlines and the researchers’ own conclusions can be justified, more research will need to be conducted, preferably through larger, longer placebo controlled studies.