W ith 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. Losing it… the challenge of diagnosing and managing cognitive impairment in older patients 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 Numbers with AD 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 Balanced data about medications The Alosa Foundation
Transcript
With the aging of the U.S. population, moreAmericans are developing dementing illnesses suchas Alzheimer’s disease.1 No treatments for theseconditions are truly satisfactory, and many causebothersome or dangerous side effects.
Addressing this problem can be one of the mostdifficult challenges in primary care; behavioral andcommunity 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 theMystery.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 ofGeriatric Psychiatry. Nov 2000;15(11):1021-1027. 3. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state".A practical method for grading the cognitivestate 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 socialcare.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). CochraneDatabase 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. Nov2005;187:450-455. 9. Spector A,Thorgrimsen L,Woods B, et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people withdementia: randomised controlled trial. Br J Psychiatry. Sep 2003;183:248-254. 10. Acevedo A, Loewenstein DA. Nonpharmacological cognitive interventions inaging 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 reviewfor 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. Behavioraland 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 indementia: benefits and harm. Nature Reviews Neuroscience. Jun 2006;7(6):492-500. 18. Ballard C,Waite J, Birks J.Atypical antipsychotics for the treatment ofaggression and psychosis in Alzheimer's disease. Cochrane Database of Systematic Reviews (Online). 2006(1):CD003476. 19. US Food and DrugAdministration. 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 NewEngland 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.orgThis 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.,AssistantProfessor 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 theCommonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Department of Public Health of theCommonwealth of Massachusetts.This material is provided by the nonprofit Alosa Foundation, which is not affiliated inany way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treatingphysician based on an individual patient’s clinical condition.
Losing it…the challenge of diagnosing andmanaging cognitive impairment in older patients
Prices of different agents vary widely; copayments can be high even for patientswith insurance.
Figure 1. Prevalence of Alzheimer’s disease by age6,000,000
5,000,000
4,000,000
3,000,000
2,000,000
1,000,000
0
Num
be
rs w
ith A
D
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
A patient should never be diagnosed with dementia unless a careful search has beenmade for other – potentially reversible – causes of cognitive decline.5 Discovering andtreating such conditions can be one of the most useful and rewarding services in thecare 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 ispresent – to gauge the severity of cognitive impairment.
No single test establishes the diagnosis of dementia. The Mini-Cog test2 can rapidlyscreen 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 andcalculation; delayed recall; and language. A full description of the MMSE is providedin the accompanying evidence document. Test scores must be interpreted in thecontext 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 trauma4-8 weeks before onset
Liver function tests
According to cause
Trial of antidepressantand/or psychotherapy
Replace T4 if underactive; treat hyperthyroidism according to cause
and symptoms
Replace, omit, or reducedose 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 isa clock face. Please put in
the hands to show 10 minutesafter 10 o’clock.”
Any impairment in the clock drawing test or item recall test warrants more detailedassessment 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.
•
A patient should never be diagnosed with dementia unless a careful search has beenmade for other – potentially reversible – causes of cognitive decline.5 Discovering andtreating such conditions can be one of the most useful and rewarding services in thecare 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 ispresent – to gauge the severity of cognitive impairment.
No single test establishes the diagnosis of dementia. The Mini-Cog test2 can rapidlyscreen 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 andcalculation; delayed recall; and language. A full description of the MMSE is providedin the accompanying evidence document. Test scores must be interpreted in thecontext 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 trauma4-8 weeks before onset
Liver function tests
According to cause
Trial of antidepressantand/or psychotherapy
Replace T4 if underactive; treat hyperthyroidism according to cause
and symptoms
Replace, omit, or reducedose 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 isa clock face. Please put in
the hands to show 10 minutesafter 10 o’clock.”
Any impairment in the clock drawing test or item recall test warrants more detailedassessment 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.
•
…then the patient is probably suffering from an age-related cause of cognitiveimpairment. The most common diagnosis is Alzheimer’s disease, but other conditionsshould be considered as well.
If no reversible cause is found…
4 5
• Memantine is generally well tolerated but can cause hypertension, dizziness, andadverse CNS and gastrointestinal effects.
• All these drugs are costly, which can be a problem for many patients (see cost charton 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
It is tempting to write a prescription as the first approach to managing cognitivedecline and the behavioral problems which may accompany it, but the drugs used forthese conditions have many limitations. Starting with behavioral and environmentalinterventions 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 cognitivedecline. 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 availabletreatments work really well, and that all can cause side effects. The products currentlyon 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 ratherthan 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), andrivastigmine (Exelon)), frequently produce anorexia, nausea, vomiting and/ordiarrhea. They can also cause adverse cardiac outcomes.
Cognitive impairment is often accompanied by behavioral disorders that range fromodd to annoying to life-threatening, and may precipitate institutional placement.15-18 Thedrugs used to treat this component of dementia generally act by sedating the patient,which can further worsen cognitive function. Benzodiazepines can sometimesprecipitate 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 behavioralproblems 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, causingthe FDA to place a black-box warning on each.19
• There is little evidence that any one antipsychotic works significantly better than anyother or placebo.
• Most of the newer ("atypical") antipsychotics substantially raise the risk of weightgain 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%
…then the patient is probably suffering from an age-related cause of cognitiveimpairment. The most common diagnosis is Alzheimer’s disease, but other conditionsshould be considered as well.
If no reversible cause is found…
4 5
• Memantine is generally well tolerated but can cause hypertension, dizziness, andadverse CNS and gastrointestinal effects.
• All these drugs are costly, which can be a problem for many patients (see cost charton 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
It is tempting to write a prescription as the first approach to managing cognitivedecline and the behavioral problems which may accompany it, but the drugs used forthese conditions have many limitations. Starting with behavioral and environmentalinterventions 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 cognitivedecline. 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 availabletreatments work really well, and that all can cause side effects. The products currentlyon 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 ratherthan 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), andrivastigmine (Exelon)), frequently produce anorexia, nausea, vomiting and/ordiarrhea. They can also cause adverse cardiac outcomes.
Cognitive impairment is often accompanied by behavioral disorders that range fromodd to annoying to life-threatening, and may precipitate institutional placement.15-18 Thedrugs used to treat this component of dementia generally act by sedating the patient,which can further worsen cognitive function. Benzodiazepines can sometimesprecipitate 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 behavioralproblems 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, causingthe FDA to place a black-box warning on each.19
• There is little evidence that any one antipsychotic works significantly better than anyother or placebo.
• Most of the newer ("atypical") antipsychotics substantially raise the risk of weightgain 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%
A summary of benefits and risks in treating patients withcognitive impairment
76
Assess and treat any underlying medical conditions that may be contributing to theproblem (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 serumglucose, weight gain), cardiac (Q-T prolongation on ECG, new onset cardiacsymptoms), 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 sideeffects occur.
Before prescribing an antipsychotic drug for an older patientwith cognitive impairment
Area Agencies on Aging (AAA) and other community services can provide usefulhelp 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 forinstitutionalization. See http://www.n4a.org/about-n4a/?fa=aaa-title-VI for nationalinformation. 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 andbehavioral problems
Efficacy
AD
DrugVD PDD DLB FTD Other GI sed EPS
OtherCNS CV incont death
Adverse effectsOverall
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
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)
valproateconventional antipsychotics
benzodiazepinesatypical antipsychotics
‡
‡‡
*
Table 3. Behavioral and psychological symptoms of dementia
A summary of benefits and risks in treating patients withcognitive impairment
76
Assess and treat any underlying medical conditions that may be contributing to theproblem (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 serumglucose, weight gain), cardiac (Q-T prolongation on ECG, new onset cardiacsymptoms), 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 sideeffects occur.
Before prescribing an antipsychotic drug for an older patientwith cognitive impairment
Area Agencies on Aging (AAA) and other community services can provide usefulhelp 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 forinstitutionalization. See http://www.n4a.org/about-n4a/?fa=aaa-title-VI for nationalinformation. 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 andbehavioral problems
Efficacy
AD
DrugVD PDD DLB FTD Other GI sed EPS
OtherCNS CV incont death
Adverse effectsOverall
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
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)
valproateconventional antipsychotics
benzodiazepinesatypical antipsychotics
‡
‡‡
*
Table 3. Behavioral and psychological symptoms of dementia
With the aging of the U.S. population, moreAmericans are developing dementing illnesses suchas Alzheimer’s disease.1 No treatments for theseconditions are truly satisfactory, and many causebothersome or dangerous side effects.
Addressing this problem can be one of the mostdifficult challenges in primary care; behavioral andcommunity 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 theMystery.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 ofGeriatric Psychiatry. Nov 2000;15(11):1021-1027. 3. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state".A practical method for grading the cognitivestate 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 socialcare.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). CochraneDatabase 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. Nov2005;187:450-455. 9. Spector A,Thorgrimsen L,Woods B, et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people withdementia: randomised controlled trial. Br J Psychiatry. Sep 2003;183:248-254. 10. Acevedo A, Loewenstein DA. Nonpharmacological cognitive interventions inaging 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 reviewfor 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. Behavioraland 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 indementia: benefits and harm. Nature Reviews Neuroscience. Jun 2006;7(6):492-500. 18. Ballard C,Waite J, Birks J.Atypical antipsychotics for the treatment ofaggression and psychosis in Alzheimer's disease. Cochrane Database of Systematic Reviews (Online). 2006(1):CD003476. 19. US Food and DrugAdministration. 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 NewEngland 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.orgThis 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.,AssistantProfessor 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 theCommonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Department of Public Health of theCommonwealth of Massachusetts.This material is provided by the nonprofit Alosa Foundation, which is not affiliated inany way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treatingphysician based on an individual patient’s clinical condition.
Losing it…the challenge of diagnosing andmanaging cognitive impairment in older patients
Prices of different agents vary widely; copayments can be high even for patientswith insurance.
Figure 1. Prevalence of Alzheimer’s disease by age6,000,000
5,000,000
4,000,000
3,000,000
2,000,000
1,000,000
0
Num
be
rs w
ith A
D
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
