Memantine is associated with fewer side effects than acetylcholinesterase inhibitors. Side effects can include dizziness, headache, and confusion. In clinical trials, more people taking placebo experienced side effects than those taking memantine. In patients with moderate to severe Alzheimer’s disease dementia receiving donepezil, the addition of memantine resulted in significantly better cognitive outcomes, function, and behavior. The addition of memantine is well tolerated in patients who are stable on an acetylcholinesterase inhibitor, said Dr. Day.
When to Stop Medication
Long-term observational data suggest a persistent effect of acetylcholinesterase inhibitors in Alzheimer’s disease dementia, with about five years of benefit in some trials. In a study that used admission to a nursing home as an outcome, the median time to admission in individuals not prescribed medication was around four to five years. The median time to admission in patients taking an acetylcholinesterase inhibitor was between eight and 10 years. There were not enough data for patients receiving combination therapy, but they may stay out of nursing homes a little longer. “There is this suggestion that use of these medications may delay admission to a nursing home,” he said.
Recommendations regarding stopping treatment vary. Some recommendations suggest that it is reasonable to discontinue these medications in patients who have transitioned to a severe dementia stage, while other recommendations suggest continuing the drugs indefinitely.
The American College of Physicians and American Academy of Family Physicians argue that if slowing decline is no longer a goal of treatment, memantine or acetylcholinesterase inhibitors are no longer appropriate.
If the family or patient’s “focus is shifting away from, ‘Let’s keep them as good as possible for as long as possible,’ to more, ‘Let’s keep them comfortable,’ then maybe removing a medication is part of that. I think it is very reasonable to consider,” Dr. Day said.
When considering stopping treatment, patients can stop medication for two weeks, and the patient and a caregiver can assess perceived cognition, function, and behaviors. If there is not a noticeable change, there is no need to restart the medication. “If they do perceive a decline, I think it is reasonable in that case to restart therapy if that is what they would like to do,” Dr. Day said. “Restarting, you simply revert back to the titration schedule that we would start whenever we’re prescribing these medications.”
Behavioral and Psychiatric Symptoms
Behavioral and psychiatric symptoms may occur in 60% to 90% of patients with dementia. These symptoms are distressing, add to caregiver burden, and are a major reason for institutionalization, Dr. Day said. Symptoms fall into four main categories: agitation, depression, apathy, and psychoses.
First, neurologists should screen for and treat any provoking causes, Dr. Day said. If a patient with a mild dementia syndrome suddenly presents with new agitation, delusions, or hallucinations, neurologists should investigate for oral ulceration, tooth problems, skin breakdown, urinary tract infection, dehydration, or visual or auditory impairment, which may contribute to or trigger these symptoms.
Otherwise, first-line treatment of agitation and psychoses entails atypical antipsychotic medication, although these treatments are not FDA-approved in patients with dementia. In patients with agitation alone, first-line therapy is behavioral interventions, although antipsychotic medications, mood stabilizers, or serotonergic compounds also can be considered. Depression and apathy may respond well to serotonergic compounds.
Black Box Warning
“Anytime we are prescribing antipsychotic medications to our patients with dementia, we need to be cognizant of the fact that these medications are prescribed off label and that they come with a black box warning,” Dr. Day said. Patients with dementia treated with antipsychotic drugs are at an increased risk of death. The risk of death appears to be greatest in those who are continued on antipsychotic medications across a three-month period. In addition, before prescribing antipsychotic medication, “you need to ask yourself—and maybe a nurse and a medical student—do you think that this patient could have dementia with Lewy bodies?” Patients with cortical Lewy bodies can experience significant morbidity or mortality due to severe neuroleptic sensitivity reactions.
Behavioral modification techniques are as effective as antipsychotic and antidepressant drugs, with fewer adverse effects, although they can be challenging to implement in a household environment.
Other Recommendations
When patients ask what else they can do to slow the progression of dementia, Dr. Day refers to seven modifiable risk factors identified in a 2014 Lancet Neurology article. These modifiable risk factors include physical inactivity, depression, midlife hypertension, midlife obesity, smoking, low educational attainment, and diabetes. In promoting physical activity, the CDC recommends a weekly exercise schedule of 150 minutes of moderate intensity activity or 75 minutes of more strenuous activity for individuals 65 and older. “That is a reasonable place to start,” Dr. Day said.