CHAPTER 18
MEMORY MEDICATIONS
WHEN AND WHAT TO CONSIDER
Medications almost always do it better if they’re used in conjunction with other supports.
MEHMET OZ, MD
When it comes to addressing memory issues, there has been general disappointment with the medications currently available. None of them cure memory problems; they help only in the moment they are taken. Memory problems have too many causes for any silver bullet to do as much as was hoped. Yet pharmaceutical companies continue to spend billions of dollars with the hope of finding the next Prozac or Viagra. If we spent the same resources and scientific effort on prevention and lifestyle interventions, we would be much further ahead. But medications do have a place and can be worth a try. If your memory problems are not responding to simpler interventions, talk with your health-care professionals about medications. In this section, I’ll review several of the most common medications and explain how we use them at Amen Clinics.
NAMENDA (MEMANTINE)
Namenda is approved for moderate to severe Alzheimer’s disease. It has been shown to boost blood flow to the prefrontal cortex and, in some cases, delay the progression of the disease in its middle stages.
The drug modulates or partly blocks a receptor called N-methyl D-aspartate (NMDA), regulating the release of the neurotransmitter glutamate. This is important because excessive production of glutamate allows too much calcium to enter cells, which then turns on genes that are programmed to kill the neurons. (One take-home message: Don’t overdo it with calcium supplements.)
Namenda sometimes produces substantial benefits in those with dementia. One of the more striking effects is the reduction in spasticity, which causes people to lose their balance, fall, or struggle to walk. Namenda can also help improve speech and fine motor skills, as well as reduce urinary incontinence. When Namenda is effective, the changes may be dramatic, easing the stress and burden on caregivers. Dosing usually starts at 5 mg a day for two weeks and is increased slowly to the maximum (typically 20 mg, although sometimes as much as 40 mg).
I’ve also seen this medication provide dramatic improvement in younger patients with mobility and speech issues. As a child, Ralph, a young man we saw at Amen Clinics, had a viral infection in his brain. Afterward, he struggled with his memory and learning. He also could no longer perform coordinated movements, speak clearly, or behave appropriately at work or in social settings. He had been fired several times because of his “poor attitude.”
His SPECT scan showed almost no activity in the cerebellum. It also showed low activity in his prefrontal cortex (affecting judgment, impulse control, and concentration) and right temporal lobe (hampering his ability to read social cues), and increased activity in the anterior cingulate gyrus (often associated with trouble shifting attention, cognitive inflexibility, and oppositional and difficult behavior). After we treated him for three months with Namenda, his family reported that his coordination, speech, behavior, and job performance had all improved. A second SPECT scan looked much better as well.
RALPH’S BRAIN SPECT SCANS (UNDERSIDE SURFACE VIEWS) BEFORE AND AFTER TREATMENT WITH NAMENDA
Before treatment: Decreased activity in PFC, right temporal lobe
After treatment: Overall improved activity
THE CHOLINESTERASE INHIBITORS (EXELON, RAZADYNE, AND ARICEPT)
As we age, acetylcholine, the neurotransmitter most often associated with memory, declines. Improving the availability of acetylcholine in the brain has been shown to help sustain memory. One way to do this is to inhibit the enzymes that break it down. These medications are called acetylcholinesterase (AChE) inhibitors, or “cholinesterase” inhibitors, and tend to work by increasing blood flow in the prefrontal cortex and temporal lobes. Three are prescribed most often.
Important differences among the cholinesterase inhibitors may determine how effectively they work in people with significant memory issues. Because acetylcholine neurons are found throughout the cerebral cortex, increasing acetylcholine can strengthen many abilities. These medications reduce behavioral problems and, in the earlier stages of Alzheimer’s disease, improve attention, short-term memory, comprehension, communication, and the ability to recognize people and objects.
Early treatment is critical, since people whose abilities are already severely impaired do not see significant gains. I have treated many patients with significant memory problems who had symptoms for less than six months, and in these patients, short-term memory has often improved.
Many patients seek help for existing problems; however, just as important is delaying or halting the progression of the disease process itself. Exelon, Razadyne, and Aricept differ most in how they seek to slow the disease.
- Exelon (rivastigmine). All three of these drugs block AChE, but only Exelon blocks butyrylcholinesterase (BuChE), the other enzyme that breaks down acetylcholine.[675] About 80 percent of the cholinesterase is AChE and 20 percent is BuChE in people who are aging normally. However, as Alzheimer’s disease (AD) progresses, the amount of AChE decreases and the amount of BuChE increases to the point where they are about equal. Both AChE and BuChE must be blocked to stall the progression of AD. At present, the only medication that does this is Exelon, which is why it is often my first choice, especially in the later stages of memory problems.
- Razadyne (galantamine). Another option is Razadyne, which does not block BuChE and cannot raise the level of acetylcholine the way that Exelon can. However, Razadyne increases the levels of many different neurotransmitters, which generally increases brain activity.[676]
- Aricept (donepezil). The first well-tolerated cholinesterase inhibitor produced in the United States, Aricept (donepezil) is now the most commonly prescribed of the cholinesterase inhibitors. (Though Cognex [tacrine] was the first cholinesterase inhibitor approved by the FDA, the medication produced many intolerable side effects and is no longer available in the United States.) Aricept is particularly effective in helping patients with mild AD, and patients report fewer side effects from it than from either Exelon or Razadyne. In addition, it needs to be given only once a day. Although its advantages make it attractive, particularly to busy physicians, it also has a couple of significant drawbacks that prevent it from being the first choice of many neurologists and psychiatrists.
Because Aricept (like Razadyne) does not block BuChE, it is less effective at blocking the accumulation of beta-amyloid plaques. Aricept (like Exelon) does not bind to the nicotinic receptor, so it does not increase overall brain activity as effectively as Razadyne, and it may not block programmed cell death.
One of my colleagues has switched hundreds of memory-loss patients who were declining on Aricept to Exelon. About half of these patients noticeably improved on Exelon. In one research study, approximately 300 people with mild to moderate dementia who showed no benefit on Aricept were switched to Exelon and treated for six months. Of this group, half showed improvements in daily activities, behavior, and/or mental abilities on Exelon.[677]
Side effects of the cholinesterase inhibitors
About 10 to 20 percent of people who take these medications experience side effects. For instance, some people become aggressive, but that often occurs with improvement in mental abilities. Fortunately, any aggression usually resolves within two weeks, and in many cases, families prefer not to stop or decrease the medication because their loved one is functioning so much better.
The primary side effects of Exelon and Razadyne are nausea, vomiting, loss of appetite, dizziness, lightheadedness or fainting, generalized weakness, and muscle pain. These side effects are not related to the stomach or heart; rather, they result from increasing acetylcholine activity in the brain stem. Groups of brain-stem neurons control vomiting (to keep you from swallowing things that will kill you), breathing, heart rate, blood pressure, and metabolism. Acetylcholine slows the heart rate, which causes a drop in blood pressure. The fainting, lightheadedness, or dizziness that results is usually not life threatening and can be managed by reducing the dose of Exelon or Razadyne.
Aricept has similar side effects to Exelon and Razadyne, but they are less frequent. Aricept can also cause nightmares in some people who take it at bedtime. However, nightmares can usually be avoided by taking Aricept in the morning instead.
STIMULATING MEDICATIONS
Stimulant medications, such as Ritalin (methylphenidate) and Adderall (amphetamine salts), have been used to help enhance focus, memory, motivation, and learning. They are classically used to treat children who have attention deficit disorder (ADD) —also known as attention deficit hyperactivity disorder (ADHD) —but I have had good success using them with people of all ages. They work by enhancing dopamine production in the basal ganglia and can increase blood flow to the prefrontal cortex and temporal lobes. If you have had ADD/ADHD symptoms throughout your life (short attention span, distractibility, disorganization, restlessness, and impulse-control issues), these meds are worth considering.
Stimulants tend to help people who have low prefrontal cortex function after a traumatic brain injury, mold exposure, or infections.[678] Research also suggests they can reduce poor decision making and apathy in those with dementia.[679]
Because of the potential for addiction and side effects, Ritalin and Adderall are often not our first choices for patients with memory issues, but they should be considered if natural treatments are ineffective.
Provigil (modafinil) and Nuvigil (armodafinil) are commonly prescribed for narcolepsy. They also have been found to heighten alertness and boost higher-order cognitive functions in many studies.[680] In my experience, these medications can help with energy, focus, and memory. They have fewer side effects than Ritalin and Adderall but also tend to have a milder effect. One of my ADD patients who could not tolerate Ritalin or Adderall (he lost his appetite and his heart raced) was able to finish his doctorate on Provigil. He said it gave him sustained focus for six to eight hours.
Other medications, like selegiline (an antidepressant), reportedly have neurotrophic, or brain-enhancing, effects, but the research has been inconsistent.
I tell my patients that the issue should never be whether they are on or off medication, but rather what supports their best functioning. If medications can help, I encourage patients to think of them like eyeglasses, which we would never withhold from someone who could benefit from them.