This document discusses the challenges of diagnosing and managing cognitive impairment in older patients. It emphasizes that a careful evaluation is needed to identify potentially reversible causes before diagnosing dementia. Screening tests like the Mini-Cog and Mini-Mental State Exam can help evaluate cognition. While medications for cognitive impairment and behavioral issues related to dementia have limitations, non-drug approaches like cognitive stimulation can help patients and caregivers cope and should be considered first.

1. With the aging of the U.S. population, more
Americans are developing dementing illnesses such
as Alzheimer’s disease.1
No treatments for these
conditions are truly satisfactory, and many cause
bothersome or dangerous side effects.
Addressing this problem can be one of the most
difficult challenges in primary care; behavioral and
community supports provide a helpful but under-
utilized approach.
References: 1. National Institute on Aging,National Institutes of Health,US Department of Health and Human Services.Alzheimer's Disease:Unraveling the
Mystery.Available at:http://www.nia.nih.gov/NR/rdonlyres/0FA2EE06-0074-4C45-BAA3-34D56170EB8B/0/Unraveling_final.pdf.2008.2. Borson S,Scanlan J,
Brush M,Vitaliano P,Dokmak A.The mini-cog:a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly.International Journal of
Geriatric Psychiatry.Nov 2000;15(11):1021-1027. 3. Folstein MF,Folstein SE,McHugh PR."Mini-mental state".A practical method for grading the cognitive
state of patients for the clinician.Journal of Psychiatric Research 1975;12(3):189-198.4. National Institute of Clinical Excellence.Donepezil,galantamine,
rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended).Technology Appraisal.Available at www.nice.org.uk/TA111.2007.
5. National Institute for Clinical Excellence.Dementia: the NICE-SCIE guideline on supporting people with dementia and their carers in health and social
care.National Clinical Practice Guideline Number 42 2007;1-391:London,The British Psychological Society &The Royal College of Psychiatrists;2007.
6. Clare L,Woods RT.Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia (Cochrane Review).Cochrane
Database of Systematic Reviews.Issue 4 Art.No.:CD003260 ed.2003:pp.DOI:10.1002/14651858.CD003260.2003.7. Knapp M,Thorgrimsen L,Patel A,et al.
Cognitive stimulation therapy for people with dementia:cost-effectiveness analysis.Br J Psychiatry.Jun 2006;188:574-580.8. Onder G,Zanetti O,Giacobini E,
et al.Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease:randomised controlled trial.Br J Psychiatry.Nov
2005;187:450-455.9. Spector A,Thorgrimsen L,Woods B,et al.Efficacy of an evidence-based cognitive stimulation therapy programme for people with
dementia:randomised controlled trial.Br J Psychiatry.Sep 2003;183:248-254.10. Acevedo A,Loewenstein DA.Nonpharmacological cognitive interventions in
aging and dementia.Journal of Geriatric Psychiatry and Neurology.Dec 2007;20(4):239-249.11. Birks J.Cholinesterase inhibitors for Alzheimer's disease
(Cochrane Review).Cochrane Database of Systematic Reviews.Issue 1 Art.No.:CD005593 ed.2006:pp.DOI:10.1002/14651858.CD005593.2006.
12. Farlow MR,Graham SM,Alvan G.Memantine for the treatment of Alzheimer's disease:tolerability and safety data from clinical trials.Drug Safety.
2008;31(7):577-585.13. Raina P,Santaguida P,Ismaila A,et al.Effectiveness of cholinesterase inhibitors and memantine for treating dementia:evidence review
for a clinical practice guideline.Ann Intern Med 2008;148:379-397.14. McShane R,Sastre A,Minakaran N.Memantine for dementia (Cochrane Review).
Cochrane Database of Systematic Reviews.Issue 2 Art.No.:CD003154 ed.2006:pp.DOI:10.1002/14651858.CD003154.pub5.2006.15. Lawlor BA.Behavioral
and psychological symptoms in dementia:the role of atypical antipsychotics.The Journal of Clinical Psychiatry.2004;65 Suppl 11:5-10.16. Byrne GJ.
Pharmacological treatment of behavioural problems in dementia.Australian Prescriber.2005;28:67-70.17. Ballard C,Howard R.Neuroleptic drugs in
dementia:benefits and harm.Nature Reviews Neuroscience.Jun 2006;7(6):492-500.18. Ballard C,Waite J,Birks J.Atypical antipsychotics for the treatment of
aggression and psychosis in Alzheimer's disease.Cochrane Database of Systematic Reviews (Online).2006(1):CD003476.19. US Food and Drug
Administration.Information for Healthcare Professionals:Antipsychotics.Available at:http://www.fda.gov/cder/drug/InfoSheets/HCP/antipsychotics_
conventional.htm.2008.20. Ray WA,Chung CP,Murray KT,Hall K,Stein CM.Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. The New
England Journal of Medicine.2009;360(3):225-235.
Additional references documenting these recommendations are provided in the evidence document accompanying this material.
visit our website: www.RxFacts.org
This material was produced by Leslie Jackowski, B.Sc.(Hon).,M.B.B.S., Research Fellow, Harvard University; Niteesh K.
Choudhry, M.D., Ph.D.,Assistant Professor of Medicine, Harvard Medical School; Michael A. Fischer, M.D., M.S.,Assistant
Professor of Medicine, Harvard Medical School and William H. Shrank, M.D., M.S.H.S.,Assistant Professor of Medicine,
Harvard Medical School. Series editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs Avorn,
Choudhry, Fischer, and Shrank are all physicians at the Brigham and Women’s Hospital in Boston.
The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the
Commonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Department of Public Health of the
Commonwealth of Massachusetts.This material is provided by the nonprofit Alosa Foundation, which is not affiliated in
any way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treating
physician based on an individual patient’s clinical condition.
©2009Alosa Foundation,all rights reserved. May 2009
Losingit…
thechallengeofdiagnosingand
managingcognitiveimpairment
inolderpatients
Prices of different agents vary widely; copayments can be high even for patients
with insurance.
Figure 1. Prevalence of Alzheimer’s disease by age
6,000,000
5,000,000
4,000,000
3,000,000
2,000,000
1,000,000
0
NumberswithAD
65 years or older
5,100,000
< 65 years old
200,000
Data from: 2009 Alzheimer’s Disease Facts and Figures. Available at: http://www.alz.org/
alzheimers_disease_facts_figures.asp
High costs despite limited effectiveness
$0 $100 $200 $300
Approximate monthly cost at maximum recommended dose
donepezil
rivastigmine*
memantine
galantamine*
Aricept $170
Exelon $202
Razadyne (immediate release) $186
Razadyne (extended release) $196
Exelon-Transdermal patch $202
Namenda $156
Prices obtained April 2009 from Epocrates online.
*FDA has recently approved the manufacture of generic galantamine and generic oral rivastigmine. Generics of donepezil,
memantine, and transdermal rivastigmine will not be available until 2010 or later.
Figure 5. Monthly costs of drugs used to treat cognitive impairment
Balanced data about medications
The Alosa Foundation
Balanced data about medications
The Alosa Foundation

2. A patient should never be diagnosed with dementia unless a careful search has been
made for other – potentially reversible – causes of cognitive decline.5
Discovering and
treating such conditions can be one of the most useful and rewarding services in the
care of the elderly.
Is there a treatable cause?
Many people over age 60 have occasional minor memory lapses; it’s critical to
distinguish these normal changes from the onset of a dementing illness, and – if one is
present – to gauge the severity of cognitive impairment.
No single test establishes the diagnosis of dementia. The Mini-Cog test2
can rapidly
screen for gross abnormalities of cognition and trigger further evaluation if needed.
The test is quick and easy to administer.
Performing well on this test does not prove that the patient has normal cognition;
more testing may be needed if symptoms persist.
Getting the diagnosis right
The Mini-Mental State Exam (MMSE) can also be easily administered in the office.3
It evaluates cognition in five areas: orientation; immediate recall; attention and
calculation; delayed recall; and language. A full description of the MMSE is provided
in the accompanying evidence document. Test scores must be interpreted in the
context of the patient's language, level of education, and developmental disability.4
Table 1. Examples of potentially reversible causes of cognitive decline
Condition Work-up
Delirium
Depression
Hypo- or hyperthyroidism
Adverse medication effect
Alcoholism or drug abuse
Vitamin B12 deficiency
Normal pressure
hydrocephalus
Subdural hematoma
Liver disease
Identify precipitating
factor(s)
Screening test (see iDiS
Depression module)
Thyroid function testing
(TSH)
Careful drug history
Careful history from
patient, caregivers
Serum B12 level
Co-existing incontinence,
gait disorder
History of head trauma
4-8 weeks before onset
Liver function tests
According to cause
Trial of antidepressant
and/or psychotherapy
Replace T4 if underactive;
treat hyperthyroidism
according to cause
and symptoms
Replace, omit, or reduce
dose of potentially
problematic drug
Substance abuse treatment
Vitamin B12 injections
Imaging studies,
neurosurgery consult
Imaging studies,
neurosurgery consult
Variable according
to cause
Treatment
2 3
Figure 2. The Mini-Cog test
1.
Ask the patient to repeat
and remember 3 items
(e.g., “ball,” “car,” “man”).
3.
Ask the patient to recall
the 3 items.
2.
Clock drawing test: “This is
a clock face. Please put in
the hands to show 10 minutes
after 10 o’clock.”
Any impairment in the clock drawing test or item recall test warrants more detailed
assessment of cognition, as with the Mini-Mental State Examination (see below).
Based on: Borson S, Scanlan J, Brush M, Vitaliano P, Dokmak A. The mini-cog: a cognitive ‘vital signs’ measure for dementia screening in
multi-lingual elderly. International Journal of Geriatric Psychiatry 2000;15(11):1021-1027.
•

3. A patient should never be diagnosed with dementia unless a careful search has been
made for other – potentially reversible – causes of cognitive decline.5
Discovering and
treating such conditions can be one of the most useful and rewarding services in the
care of the elderly.
Is there a treatable cause?
Many people over age 60 have occasional minor memory lapses; it’s critical to
distinguish these normal changes from the onset of a dementing illness, and – if one is
present – to gauge the severity of cognitive impairment.
No single test establishes the diagnosis of dementia. The Mini-Cog test2
can rapidly
screen for gross abnormalities of cognition and trigger further evaluation if needed.
The test is quick and easy to administer.
Performing well on this test does not prove that the patient has normal cognition;
more testing may be needed if symptoms persist.
Getting the diagnosis right
The Mini-Mental State Exam (MMSE) can also be easily administered in the office.3
It evaluates cognition in five areas: orientation; immediate recall; attention and
calculation; delayed recall; and language. A full description of the MMSE is provided
in the accompanying evidence document. Test scores must be interpreted in the
context of the patient's language, level of education, and developmental disability.4
Table 1. Examples of potentially reversible causes of cognitive decline
Condition Work-up
Delirium
Depression
Hypo- or hyperthyroidism
Adverse medication effect
Alcoholism or drug abuse
Vitamin B12 deficiency
Normal pressure
hydrocephalus
Subdural hematoma
Liver disease
Identify precipitating
factor(s)
Screening test (see iDiS
Depression module)
Thyroid function testing
(TSH)
Careful drug history
Careful history from
patient, caregivers
Serum B12 level
Co-existing incontinence,
gait disorder
History of head trauma
4-8 weeks before onset
Liver function tests
According to cause
Trial of antidepressant
and/or psychotherapy
Replace T4 if underactive;
treat hyperthyroidism
according to cause
and symptoms
Replace, omit, or reduce
dose of potentially
problematic drug
Substance abuse treatment
Vitamin B12 injections
Imaging studies,
neurosurgery consult
Imaging studies,
neurosurgery consult
Variable according
to cause
Treatment
2 3
Figure 2. The Mini-Cog test
1.
Ask the patient to repeat
and remember 3 items
(e.g., “ball,” “car,” “man”).
3.
Ask the patient to recall
the 3 items.
2.
Clock drawing test: “This is
a clock face. Please put in
the hands to show 10 minutes
after 10 o’clock.”
Any impairment in the clock drawing test or item recall test warrants more detailed
assessment of cognition, as with the Mini-Mental State Examination (see below).
Based on: Borson S, Scanlan J, Brush M, Vitaliano P, Dokmak A. The mini-cog: a cognitive ‘vital signs’ measure for dementia screening in
multi-lingual elderly. International Journal of Geriatric Psychiatry 2000;15(11):1021-1027.
•

4. …then the patient is probably suffering from an age-related cause of cognitive
impairment. The most common diagnosis is Alzheimer’s disease, but other conditions
should be considered as well.
If no reversible cause is found…
4 5
• Memantine is generally well tolerated but can cause hypertension, dizziness, and
adverse CNS and gastrointestinal effects.
• All these drugs are costly, which can be a problem for many patients (see cost chart
on page 8).
Dealing with the behavioral problems of dementia
Figure 4. Adjusted incidence-rate-ratios for sudden cardiac death among current
users of antipsychotic drugs compared to nonusers, and according to type of
drug and dose20
3.5
3
2.5
2
1.5
1
0.5
0
Atypical antipsychotic agentTypical antipsychotic agent
Low dose
Adapted with permission from Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical Antipsychotic Drugs and the Risk of Sudden
Cardiac Death. NEJM. 2009;360(3):225-235. Copyright © 2009 Massachusetts Medical Society. All rights reserved
1.31
2.01
2.42
1.59
2.86
2.13
Moderate dose
High dose
It is tempting to write a prescription as the first approach to managing cognitive
decline and the behavioral problems which may accompany it, but the drugs used for
these conditions have many limitations. Starting with behavioral and environmental
interventions can be effective, safer, and more affordable.
Some non-drug approaches can make it easier for patients and caregivers to cope
with reduced memory,5, 6
although few have been clearly shown to help with cognitive
decline. The best-studied include cognitive stimulation, spaced-retrieval technique,
procedural motor memory training, and dual cognitive support5, 7-10
(see evidence document).
Begin with non-drug approaches
The prescriber, patient, and caregivers must keep in mind that none of the available
treatments work really well, and that all can cause side effects. The products currently
on the market have shown statistical superiority over placebo, but in many studies this
“advantage” may have been just a few points of change on a psychometric scale rather
than a clinically noticeable improvement.11-14
• All currently available drugs for cognitive impairment work about as well as
each other.11
• The cholinesterase inhibitors (donepezil (Aricept), galantamine (Razadyne), and
rivastigmine (Exelon)), frequently produce anorexia, nausea, vomiting and/or
diarrhea. They can also cause adverse cardiac outcomes.
Cognitive impairment is often accompanied by behavioral disorders that range from
odd to annoying to life-threatening, and may precipitate institutional placement.15-18
The
drugs used to treat this component of dementia generally act by sedating the patient,
which can further worsen cognitive function. Benzodiazepines can sometimes
precipitate a paradoxical reaction that makes the patient more, rather than less agitated.
Antipsychotic drugs such as risperidone (Risperdal), olanzapine (Zyprexa),
haloperidol, and quetiapine (Seroquel) have been widely used to manage behavioral
problems in older patients with dementia, but there are problems with this approach.
• No antipsychotic agent has been FDA-approved for behavioral symptoms in the
elderly.19
• Both conventional and atypical antipsychotics can increase the risk of death, causing
the FDA to place a black-box warning on each.19
• There is little evidence that any one antipsychotic works significantly better than any
other or placebo.
• Most of the newer ("atypical") antipsychotics substantially raise the risk of weight
gain and diabetes.
Drug treatment for cognitive impairment
Figure 3. Cause of dementia in people over age 70
Data from: 2009 Alzheimer’s Disease Facts
and Figures. Available at: http://www.alz.org/
alzheimers_disease_facts_figures.asp
Alzheimer’s disease, 70%
Vascular dementia, 17%
Other dementia, 13%

5. …then the patient is probably suffering from an age-related cause of cognitive
impairment. The most common diagnosis is Alzheimer’s disease, but other conditions
should be considered as well.
If no reversible cause is found…
4 5
• Memantine is generally well tolerated but can cause hypertension, dizziness, and
adverse CNS and gastrointestinal effects.
• All these drugs are costly, which can be a problem for many patients (see cost chart
on page 8).
Dealing with the behavioral problems of dementia
Figure 4. Adjusted incidence-rate-ratios for sudden cardiac death among current
users of antipsychotic drugs compared to nonusers, and according to type of
drug and dose20
3.5
3
2.5
2
1.5
1
0.5
0
Atypical antipsychotic agentTypical antipsychotic agent
Low dose
Adapted with permission from Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical Antipsychotic Drugs and the Risk of Sudden
Cardiac Death. NEJM. 2009;360(3):225-235. Copyright © 2009 Massachusetts Medical Society. All rights reserved
1.31
2.01
2.42
1.59
2.86
2.13
Moderate dose
High dose
It is tempting to write a prescription as the first approach to managing cognitive
decline and the behavioral problems which may accompany it, but the drugs used for
these conditions have many limitations. Starting with behavioral and environmental
interventions can be effective, safer, and more affordable.
Some non-drug approaches can make it easier for patients and caregivers to cope
with reduced memory,5, 6
although few have been clearly shown to help with cognitive
decline. The best-studied include cognitive stimulation, spaced-retrieval technique,
procedural motor memory training, and dual cognitive support5, 7-10
(see evidence document).
Begin with non-drug approaches
The prescriber, patient, and caregivers must keep in mind that none of the available
treatments work really well, and that all can cause side effects. The products currently
on the market have shown statistical superiority over placebo, but in many studies this
“advantage” may have been just a few points of change on a psychometric scale rather
than a clinically noticeable improvement.11-14
• All currently available drugs for cognitive impairment work about as well as
each other.11
• The cholinesterase inhibitors (donepezil (Aricept), galantamine (Razadyne), and
rivastigmine (Exelon)), frequently produce anorexia, nausea, vomiting and/or
diarrhea. They can also cause adverse cardiac outcomes.
Cognitive impairment is often accompanied by behavioral disorders that range from
odd to annoying to life-threatening, and may precipitate institutional placement.15-18
The
drugs used to treat this component of dementia generally act by sedating the patient,
which can further worsen cognitive function. Benzodiazepines can sometimes
precipitate a paradoxical reaction that makes the patient more, rather than less agitated.
Antipsychotic drugs such as risperidone (Risperdal), olanzapine (Zyprexa),
haloperidol, and quetiapine (Seroquel) have been widely used to manage behavioral
problems in older patients with dementia, but there are problems with this approach.
• No antipsychotic agent has been FDA-approved for behavioral symptoms in the
elderly.19
• Both conventional and atypical antipsychotics can increase the risk of death, causing
the FDA to place a black-box warning on each.19
• There is little evidence that any one antipsychotic works significantly better than any
other or placebo.
• Most of the newer ("atypical") antipsychotics substantially raise the risk of weight
gain and diabetes.
Drug treatment for cognitive impairment
Figure 3. Cause of dementia in people over age 70
Data from: 2009 Alzheimer’s Disease Facts
and Figures. Available at: http://www.alz.org/
alzheimers_disease_facts_figures.asp
Alzheimer’s disease, 70%
Vascular dementia, 17%
Other dementia, 13%

6. A summary of benefits and risks in treating patients with
cognitive impairment
76
Assess and treat any underlying medical conditions that may be contributing to the
problem (e.g., pain, delirium, depression).
Review any medications that may be implicated (e.g., anticholinergics, psychotropics).
Identify one or more target behaviors that warrant drug treatment.
Consider whether these behaviors pose a risk to the patient or others, or are merely
a nuisance.
Determine the behavioral goal being sought for each target problem, and how it
will be assessed.
Implement all practical environmental and behavioral interventions.
Start with the lowest possible dose if a drug must be used.
Monitor carefully for expected side effects, including metabolic (increase in serum
glucose, weight gain), cardiac (Q-T prolongation on ECG, new onset cardiac
symptoms), and behavioral (excessive sedation, worsening of cognitive impairment).
Reassess the need for medication regularly.
Reduce dose or stop treatment if target behaviors improve or if unacceptable side
effects occur.
Before prescribing an antipsychotic drug for an older patient
with cognitive impairment
Area Agencies on Aging (AAA) and other community services can provide useful
help to older patients and their families in coping with cognitive impairment.
Sometimes this can enable a person to remain at home and avoid or delay the need for
institutionalization. See http://www.n4a.org/about-n4a/?fa=aaa-title-VI for national
information. Information specific to Pennsylvania is at http://www.aging.state.pa.us/
aging/cwp/view.asp?a=275&Q=177124.
Whether or not medications are used, community resources
are an essential part of managing patients with memory and
behavioral problems
Efficacy
AD
Drug
VD PDD DLB FTD Other GI sed EPS
Other
CNS CV incont death
Adverse effects
Overall
AD = Alzheimer’s disease; VD = vascular dementia; PDD = Parkinson’s disease dementia;
DLB = dementia with Lewy bodies; FTD = fronto-temporal dementia; Other = other forms of dementia;
GI = gastrointestinal; sed = sedation; CNS = central nervous system (e.g., seizures);
CV = cardiovascular; incont = incontinence; EPS = extrapyramidal symptoms
donepezil (Aricept)
Best outcome Intermediate Problem
galantamine (Razadyne)
conventional antipsychotics
atypical antipsychotics
rivastigmine (Exelon)
memantine (Namenda)
Unknown or no effect
Table 2. Cognition
Symptom
controlDrug
GI sed EPS
Other
CNS CV incont death
Adverse effects
Overall
GI = gastrointestinal; sed = sedation; CNS = central nervous system (e.g., seizures);
CV = cardiovascular; incont = incontinence; EPS = extrapyramidal symptoms
‡
May modestly improve behavioral symptoms (in particular visual hallucinations) in patients with DLB.
‡‡
Some evidence of efficacy for delusions, agitation, and aggression, but unclear whether the drug produces important clinical benefit.
* Valproate is commonly used for this indication but there is little evidence supporting its efficacy.
rivastigmine (Exelon)
memantine (Namenda)
valproate
conventional antipsychotics
benzodiazepines
atypical antipsychotics
‡
‡‡
*
Table 3. Behavioral and psychological symptoms of dementia

7. A summary of benefits and risks in treating patients with
cognitive impairment
76
Assess and treat any underlying medical conditions that may be contributing to the
problem (e.g., pain, delirium, depression).
Review any medications that may be implicated (e.g., anticholinergics, psychotropics).
Identify one or more target behaviors that warrant drug treatment.
Consider whether these behaviors pose a risk to the patient or others, or are merely
a nuisance.
Determine the behavioral goal being sought for each target problem, and how it
will be assessed.
Implement all practical environmental and behavioral interventions.
Start with the lowest possible dose if a drug must be used.
Monitor carefully for expected side effects, including metabolic (increase in serum
glucose, weight gain), cardiac (Q-T prolongation on ECG, new onset cardiac
symptoms), and behavioral (excessive sedation, worsening of cognitive impairment).
Reassess the need for medication regularly.
Reduce dose or stop treatment if target behaviors improve or if unacceptable side
effects occur.
Before prescribing an antipsychotic drug for an older patient
with cognitive impairment
Area Agencies on Aging (AAA) and other community services can provide useful
help to older patients and their families in coping with cognitive impairment.
Sometimes this can enable a person to remain at home and avoid or delay the need for
institutionalization. See http://www.n4a.org/about-n4a/?fa=aaa-title-VI for national
information. Information specific to Pennsylvania is at http://www.aging.state.pa.us/
aging/cwp/view.asp?a=275&Q=177124.
Whether or not medications are used, community resources
are an essential part of managing patients with memory and
behavioral problems
Efficacy
AD
Drug
VD PDD DLB FTD Other GI sed EPS
Other
CNS CV incont death
Adverse effects
Overall
AD = Alzheimer’s disease; VD = vascular dementia; PDD = Parkinson’s disease dementia;
DLB = dementia with Lewy bodies; FTD = fronto-temporal dementia; Other = other forms of dementia;
GI = gastrointestinal; sed = sedation; CNS = central nervous system (e.g., seizures);
CV = cardiovascular; incont = incontinence; EPS = extrapyramidal symptoms
donepezil (Aricept)
Best outcome Intermediate Problem
galantamine (Razadyne)
conventional antipsychotics
atypical antipsychotics
rivastigmine (Exelon)
memantine (Namenda)
Unknown or no effect
Table 2. Cognition
Symptom
controlDrug
GI sed EPS
Other
CNS CV incont death
Adverse effects
Overall
GI = gastrointestinal; sed = sedation; CNS = central nervous system (e.g., seizures);
CV = cardiovascular; incont = incontinence; EPS = extrapyramidal symptoms
‡
May modestly improve behavioral symptoms (in particular visual hallucinations) in patients with DLB.
‡‡
Some evidence of efficacy for delusions, agitation, and aggression, but unclear whether the drug produces important clinical benefit.
* Valproate is commonly used for this indication but there is little evidence supporting its efficacy.
rivastigmine (Exelon)
memantine (Namenda)
valproate
conventional antipsychotics
benzodiazepines
atypical antipsychotics
‡
‡‡
*
Table 3. Behavioral and psychological symptoms of dementia

8. With the aging of the U.S. population, more
Americans are developing dementing illnesses such
as Alzheimer’s disease.1
No treatments for these
conditions are truly satisfactory, and many cause
bothersome or dangerous side effects.
Addressing this problem can be one of the most
difficult challenges in primary care; behavioral and
community supports provide a helpful but under-
utilized approach.
References: 1. National Institute on Aging,National Institutes of Health,US Department of Health and Human Services.Alzheimer's Disease:Unraveling the
Mystery.Available at:http://www.nia.nih.gov/NR/rdonlyres/0FA2EE06-0074-4C45-BAA3-34D56170EB8B/0/Unraveling_final.pdf.2008.2. Borson S,Scanlan J,
Brush M,Vitaliano P,Dokmak A.The mini-cog:a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly.International Journal of
Geriatric Psychiatry.Nov 2000;15(11):1021-1027. 3. Folstein MF,Folstein SE,McHugh PR."Mini-mental state".A practical method for grading the cognitive
state of patients for the clinician.Journal of Psychiatric Research 1975;12(3):189-198.4. National Institute of Clinical Excellence.Donepezil,galantamine,
rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended).Technology Appraisal.Available at www.nice.org.uk/TA111.2007.
5. National Institute for Clinical Excellence.Dementia: the NICE-SCIE guideline on supporting people with dementia and their carers in health and social
care.National Clinical Practice Guideline Number 42 2007;1-391:London,The British Psychological Society &The Royal College of Psychiatrists;2007.
6. Clare L,Woods RT.Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia (Cochrane Review).Cochrane
Database of Systematic Reviews.Issue 4 Art.No.:CD003260 ed.2003:pp.DOI:10.1002/14651858.CD003260.2003.7. Knapp M,Thorgrimsen L,Patel A,et al.
Cognitive stimulation therapy for people with dementia:cost-effectiveness analysis.Br J Psychiatry.Jun 2006;188:574-580.8. Onder G,Zanetti O,Giacobini E,
et al.Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease:randomised controlled trial.Br J Psychiatry.Nov
2005;187:450-455.9. Spector A,Thorgrimsen L,Woods B,et al.Efficacy of an evidence-based cognitive stimulation therapy programme for people with
dementia:randomised controlled trial.Br J Psychiatry.Sep 2003;183:248-254.10. Acevedo A,Loewenstein DA.Nonpharmacological cognitive interventions in
aging and dementia.Journal of Geriatric Psychiatry and Neurology.Dec 2007;20(4):239-249.11. Birks J.Cholinesterase inhibitors for Alzheimer's disease
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and psychological symptoms in dementia:the role of atypical antipsychotics.The Journal of Clinical Psychiatry.2004;65 Suppl 11:5-10.16. Byrne GJ.
Pharmacological treatment of behavioural problems in dementia.Australian Prescriber.2005;28:67-70.17. Ballard C,Howard R.Neuroleptic drugs in
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Additional references documenting these recommendations are provided in the evidence document accompanying this material.
visit our website: www.RxFacts.org
This material was produced by Leslie Jackowski, B.Sc.(Hon).,M.B.B.S., Research Fellow, Harvard University; Niteesh K.
Choudhry, M.D., Ph.D.,Assistant Professor of Medicine, Harvard Medical School; Michael A. Fischer, M.D., M.S.,Assistant
Professor of Medicine, Harvard Medical School and William H. Shrank, M.D., M.S.H.S.,Assistant Professor of Medicine,
Harvard Medical School. Series editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs Avorn,
Choudhry, Fischer, and Shrank are all physicians at the Brigham and Women’s Hospital in Boston.
The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the
Commonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Department of Public Health of the
Commonwealth of Massachusetts.This material is provided by the nonprofit Alosa Foundation, which is not affiliated in
any way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treating
physician based on an individual patient’s clinical condition.
©2009Alosa Foundation,all rights reserved. May 2009
Losingit…
thechallengeofdiagnosingand
managingcognitiveimpairment
inolderpatients
Prices of different agents vary widely; copayments can be high even for patients
with insurance.
Figure 1. Prevalence of Alzheimer’s disease by age
6,000,000
5,000,000
4,000,000
3,000,000
2,000,000
1,000,000
0
NumberswithAD
65 years or older
5,100,000
< 65 years old
200,000
Data from: 2009 Alzheimer’s Disease Facts and Figures. Available at: http://www.alz.org/
alzheimers_disease_facts_figures.asp
High costs despite limited effectiveness
$0 $100 $200 $300
Approximate monthly cost at maximum recommended dose
donepezil
rivastigmine*
memantine
galantamine*
Aricept $170
Exelon $202
Razadyne (immediate release) $186
Razadyne (extended release) $196
Exelon-Transdermal patch $202
Namenda $156
Prices obtained April 2009 from Epocrates online.
*FDA has recently approved the manufacture of generic galantamine and generic oral rivastigmine. Generics of donepezil,
memantine, and transdermal rivastigmine will not be available until 2010 or later.
Figure 5. Monthly costs of drugs used to treat cognitive impairment
Balanced data about medications
The Alosa Foundation
Balanced data about medications
The Alosa Foundation