Alzheimer's disease is the most common form of dementia. Dementia is when you lose your memory, problem-solving skills, language, and other abilities related to how you think – to the extent that your everyday life is disrupted.
The single biggest risk factor for Alzheimer's is aging. Drugs used to treat Alzheimer's give some people who have it a little relief from symptoms. But they don’t stop its unavoidable progress. So researchers are looking at newer therapies that may be able to slow down the progression.
Two therapies being studied are transcranial magnetic stimulation and deep brain stimulation. Brain stimulation therapies use electricity to “turn on” or “turn off” certain activity in the brain.
Repetitive Transcranial Magnetic Stimulation (rTMS)
What is it and how does it work?
Transcranial magnetic stimulation (TMS) is one of the newer therapies for people with Alzheimer’s disease. It uses a magnet to switch on a part of your brain. The therapy is done in daily sessions five times a week, so it’s called “repetitive” TMS or rTMS.
The rTMS sessions happen over 4-6 weeks. The sessions are noninvasive (meaning they don’t require surgery) and can be done at a doctor’s office or clinic, without anesthesia. An electromagnetic coil is placed against your head. It’s switched on and off repeatedly, producing pulses. Each pulse produces a clicking sound that lasts a few seconds. You’ll feel tapping on your forehead.
Exactly how rTMS works in people with Alzheimer's is not well understood. Researchers think this type of brain stimulation can speed up or slow down brain activity in ways that improve cognitive problems.
How effective is it?
The potential effectiveness of rTMS depends on the type of stimulation and how it’s given. For example, stimulation can be low frequency or high frequency. It can be done in a regular rhythm or in a “patterned” rhythm that imitates specific types of brain activity.
Low-frequency stimulation seems to slow down brain activity. High-frequency stimulation seems to increase it. Other factors that influence how effective it is include which area of the brain is targeted and how far away the stimulation is from that area. If the person with Alzheimer's takes certain medications, that can also make a difference.
Researchers have tested rTMS therapy for Alzheimer's since 2012. Effectiveness is measured in different ways, including improved mental states, ability to do everyday activities, and recognition. In general, high-frequency stimulation is more effective for those with mild dementia than severe cases. In some cases, improvements in cognitive function happen immediately after rTMS. But they can take as long as 6 weeks to appear. These benefits can then last for 3 months or even longer. Studies suggest that how a person responds to rTMS may depend on how often they get the stimulation and how much memory loss they had to begin with. A study also suggests people with very bad dementia who got rTMS showed no improvement, no matter how often they got it.
rTMS is sometimes combined with cognitive training. This is sometimes called “brain training.” It involves guided drills and activities to improve the way your brain works. Training can be given either at the same time you get rTMS or 6 weeks afterward. When cognitive training relates to the same region of the brain being targeted by rTMS, certain brain activities can improve within 6 weeks and continue as long as 4 1/2 months later. Combined treatment is more effective in those with mild to moderate Alzheimer's.
The FDA approved rTMS in 2008 for hard-to-treat depression. As many as half of people with Alzheimer’s have depression. And others likely will have symptoms of depression. That makes it hard to know exactly what effects of rTMS on Alzheimer's are related to treating the depression.
The small amount of research on using rTMS for Alzheimer's makes it somewhat difficult to predict effectiveness. For example, some people may get better at taking a specific test (to determine if therapy is effective) repeatedly and not as a result of the rTMS itself.
What are the side effects, complications, and outlook?
Side effects: The place on your head closest to the magnet could feel uncomfortable. You might feel tingling in your jaw, scalp, or face. You may get a headache or lightheadedness. One serious but uncommon side effect of rTMS is seizure. And not much is known about the possibility of any long-term side effects.
Complications. High-frequency stimulation is the most studied type of rTMS. It produces good results in mild cases of Alzheimer's. But some researchers wonder if this same high-frequency stimulation might also cause Alzheimer's to get worse. More research is needed on this issue and others.
Outlook. A 2022 review of research showed people with Alzheimer's who were treated with rTMS had improved cognitive function compared with those who were not. But there were no effects on their attention, language, memory, and executive function (things like getting organized, prioritizing, focusing on tasks until they’re finished, and keeping a check on emotions).
In 2019, an FDA panel rejected a brain-stimulation device (which is approved to treat Alzheimer's in Europe, Australia, and Israel) that combines rTMS with cognitive training to improve memory function in early-stage Alzheimer's. The panel said while rTMS may be beneficial in treating Alzheimer's, better clinical trials are needed.
Deep Brain Stimulation
What is it and how does it work?
In contrast to rTMS, deep brain stimulation (DBS) is invasive. That means it requires brain surgery. During the procedure, a pair of electrodes is implanted in your brain. Small generators that will control the electrodes are implanted in your chest.
You’ll get an MRI scan of your head and brain. You’ll be awake during the procedure, with a local anesthetic to make your head numb (the brain does not feel pain). Then the surgeon will drill two holes in your head and use the MRI images to put the electrodes in just the right place. Then, you’ll go under general anesthesia (be put to sleep) so the surgeon can implant the generators and the wires connecting them to the electrodes. After surgery, brain stimulation is continuous. The doctor will customize how often you’ll get the stimulation and how intense it will be.
Deep brain stimulation was first used to reduce the tremors, stiffness, and uncontrollable movements of Parkinson’s disease. Researchers started to look at its use in Alzheimer's after one patient’s memory improved when she received DBS treatment for obesity.
Since then, people with Alzheimer's who are treated with DBS have had positive results. Researchers are still trying to figure out the best way to use DBS for Alzheimer's – including which parts of the brain to stimulate, how strong the stimulation should be, and how long the stimulation should last.
DBS when used for Alzheimer's disease targets areas of the brain that include important neural pathways, such as:
- VC/VS (ventral capsule/ventral striatum), which is involved in cognition (thinking, logic, and remembering) and behavior
- ILN (intralaminar thalamic nucleus), an important part of cognitive function
- MTN (midline thalamic nuclei), which is involved in memory
- NBM (nucleus basalis of Meynert), part of an important pathway related to cognition and memory
Researchers don’t know exactly how DBS works to treat Alzheimer's. One theory is that the stimulation helps balance nerve networks that may have become out of sync. Another theory is that DBS resets unstable nerve movements. Still another is that DBS reduces levels of plaques that are toxic to nerves in key areas of the brain.
How effective is it?
Early studies show DBS is a promising treatment. How effective it is depends on the stage of the disease and the specific treatment plan (brain area targeted, how often it gets stimulated, and more).
In general, DBS is most effective when used in early-stage Alzheimer's. People with late-onset Alzheimer’s get a small benefit from DBS – they seem to decline more slowly. People with early-onset Alzheimer's (those diagnosed before age 65) show no benefit.
What are the potential complications, side effects, and outlook?
Complications. Complications from the surgery include bleeding, infection, and hardware failure. Other complications relate to how intense the voltage is. Those include:
- Restlessness
- Warmth
- Flushing
- Sweating
- An increase in your blood pressure
- Faster heart rate
Finding the best stimulation frequency (which can vary by person and treatment) can help ease side effects.
The side effects of DBS include:
- Infection
- Bleeding in the brain or stroke
- Confusion
- Lightheadedness
- Mood changes
- Trouble sleeping
In one study of DBS for Alzheimer's, some people had falls, seizures, and fainting. All those side effects are similar to ones you might get with certain Alzheimer's medications.
In the largest clinical trial of DBS for Alzheimer's, more than half of the people had side effects that were not considered serious. Some side effects may appear and then go away, including headache, diarrhea, vomiting, and tingling. Many negative effects improve as time passes after surgery. There were no long-term negative effects. But another study did report long-term bad effects.
Outlook. DBS treatment for Alzheimer's looks promising, but there’s still a lot to learn. Many studies so far have limitations, and DBS is an invasive technique with risks.
Clinical trials:
For more information about clinical trials on brain stimulation treatment for Alzheimer's, see Brain Stimulation Therapies at clinicaltrials.gov.
