THE QUESTION
My father has been diagnosed with Alzheimer's disease. Are there any medications that can help him?
THE ANSWER
Unfortunately, there are no drugs that can cure Alzheimer's disease, or halt the inevitable advance of the mind-robbing condition.
But a handful of medications can – at least for a while – help ease some of the symptoms, such as memory loss and troubles with focus and attention.
Studies involving large groups of patients have shown that the overall benefits of these drugs are "only modest," says Dr. Mario Masellis, a neurologist and clinician-scientist at Sunnybrook Health Sciences Centre.
However, some patients show more of an improvement than others, he adds.
To better understand the potential upside and downside of these drugs, it's worthwhile knowing more about the underlying disease.
Alzheimer's is characterized by a build-up of two proteins in the brain.
One protein is called beta amyloid, which accumulates as a sticky plaque around brain cells known as neurons. It is believed that amyloid plaque is involved in the dysfunction of synapses – or connections – between neurons.
The other telltale protein is tau, which forms "neurofibrillary tangles" inside neurons and contributes to their degeneration.
Over time, brain cells that play a key role in memory formation begin to die. Some of these cells normally produce acetylcholine, which is a neurotransmitter – or chemical messenger – that enables brain cells to "speak" to one another.
Most of the existing Alzheimer's drugs are designed to boost the level of acetylcholine by slowing its breakdown in the brain. That essentially means the available acetylcholine can do more because it lasts longer – despite the dwindling production.
In Canada, there are three drugs approved for this purpose. Known as cholinesterase inhibitors, they include donepezil (brand name Aricept), galantamine (Reminyl) and rivastigmine (Exelon).
These drugs are usually started in the early to middle stages of the disease and the response varies from patient to patient. Some actually see an improvement in their memory and have an increased ability to concentrate, says Masellis. Others may experience a slowing in their rate of decline in cognition. Eventually, though, cholinesterase inhibitors lose their effectiveness as more and more acetylcholine-producing cells die.
It's also important to be aware that these drugs, especially when taken in pill form, can cause nausea, vomiting and diarrhea in some patients.
In the later stages of the disease, doctors may prescribe a different type of drug called memantine (Ebixa) that affects glutamate – another chemical messaging system that goes awry. As more and more brain cells die, glutamate levels soar in the brain. Excess glutamate can "overstimulate" certain neurons and may cause personality changes, agitation, and confusion. Memantine is believed to help reduce these symptoms by blocking glutamate receptors. But there is a risk that memantine will backfire and have the opposite effect on some patients, increasing agitation and confusion, says Masellis.
Alzheimer's patients can also become depressed, in part, because of the loss of yet another chemical massenger – serotonin. Doctors may prescribe a type of antidepressant known as an SSRI (selective serotonin reuptake inhibitor) that boosts serotonin levels. "An SSRI can help with mood and have a calming effect, making the patient less irritable," says Masellis.
Furthermore, some patients develop psychotic symptoms that include hallucinations and paranoid behaviour.
To treat these symptoms, patients may be prescribed antipsychotic drugs. But Masellis warns that these medications should be used sparingly because they can cause troubling side effects, such as confusion, sedation, muscular rigidity and significant weight gain.
It certainly would be worthwhile to have medications that reverse the underlying brain changes that are linked to Alzheimer's. And, in fact, there have been countless studies of experimental drugs that tried to rid the brain of amyloid plaques. But, so far, none of the studies has demonstrated a meaningful change in patients – even when some of the abnormal protein was cleared from the brain.
Many researchers now believe treatment must be started very early in the course of the disease. By the time the proteins accumulate, the damage may be irreversible. So, prevention trials are now being carried out on patients who may be genetically predisposed to getting the dreaded condition.
But, to further complicate matters, some experts aren't convinced that amyloid and tau in isolation are the sole cause of Alzheimer's dementia. There is increasing evidence that damage to the blood vessels may also be involved in the dementing process.
With so much still unknown about Alzheimer's, it's unlikely there will be a transformative treatment any time soon. In the absence of a cure, Masellis believes patients should try what's currently available. "This is a slowly progressing disorder that gets worse over time," he says. For some patients, the medications may at least help them carry out their daily activities for a bit longer than would otherwise be the case.
Paul Taylor is a patient navigation adviser at Sunnybrook Health Sciences Centre. He is a former Health Editor of The Globe and Mail. You can find him on Twitter @epaultaylor and online at Sunnybrook's Your Health Matters.