Symptomatic Management of Dementia

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

“In dealing with neurodegenerative progressive illnesses, the kinds of treatments that [patients] require may change as the disease changes. We have to be in tune to that. We also have to be prepared to manage the diverse set of symptoms that any one individual can experience,” Dr. Day said.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

 

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.

 

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

“In dealing with neurodegenerative progressive illnesses, the kinds of treatments that [patients] require may change as the disease changes. We have to be in tune to that. We also have to be prepared to manage the diverse set of symptoms that any one individual can experience,” Dr. Day said.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

 

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.

 

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

“In dealing with neurodegenerative progressive illnesses, the kinds of treatments that [patients] require may change as the disease changes. We have to be in tune to that. We also have to be prepared to manage the diverse set of symptoms that any one individual can experience,” Dr. Day said.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

 

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.

 

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly