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Alzheimer’s News. Know the 10 Signs: Early Detection Matters. E-newletter. Alz Assn. 2009. Last accessed online Dec 2015. http://www.alz.org/national/documents/checklist_10signs.pdf
Landau SM, Harvey D et al. Comparing predictors of conversion and decline in mild cognitive impairment. Neurology. 2010 Jul 20;75(3):230-8.
1. Mayo clinic Nov 2011.Porter RS. The Merck Manual of Diagnosis and Therapy Nineteenth Edition. July 2011.
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Holsinger T, Plassman BL. et al. Screening for Cognitive Impairment: Comparing the Performance of Four Instruments in Primary Care. J Am Geriatr Soc. 2012;60(6):1027-1036
Galvin JE et al. Neurology. 2005;65:559-564
Lopes M, Brucki SMD, Giampaoli V, Mansur LL. Semantic Verbal Fluency test in dementia: Preliminary retrospective analysis. Dement. Neuropsychol. 2009;3(4):315-320
Borson S, Scanlan JM et al. Improving identification of cognitive impairment in primary care. Int J Geriatr Psychiatry 2006; 21(4):349–355.
Aprahamian, I, Martinelli, JE et al. The Clock Drawing Test:A review of its accuracy in screening for dementia. Dement. Neuropsychol. 2009 June;3(2):74-80.
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Folstein MF, Folstein SE, McHugh PR. "Mini-mental state." A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12: 189-198.
http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf
Tariq SH, Tumosa N, Chibnall JT, et al. Comparison of the Saint Louis University Mental Status Examination and the Mini-Mental State Examination for detecting dementia and mild neurocognitive disorder: a pilot study. Am J Geriatr Psychiatry. 2006;14:900-910.
http://www.mocatest.org/pdf_files/test/MoCA-Test-English_7_1.pdf
Koski L, Haiqun X. Measuring Cognition in a Geriatric Outpatient Clinic: Rasch Analysis of the Montreal Cognitive Assessment. J Geriatr Psychiatry Neurol. 2009; 22(3): 151-160
• http://img.medscape.com/pi/emed/ckb/psychiatry/285911-1335300-1356106-1392041.pdf
• http://www.depression-primarycare.org/images/pdf/phq_9_eng.pdf
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American Psychiatric Association, 1997; Lobo A, et al. Neurology. 2000;54(suppl 5):S4-S9; Morris JC. Clin Geriatr Med. 1994;10:257-276; Small GW, et al. JAMA. 1997;278:1363-1371.
5% 10% 64% 6% 9% 6%
Dementia with Lewy bodiesParkinson’s dementia
Diffuse Lewy body diseaseVascular dementias and AD
Other dementias(eg, Frontotemporal dementia
Creutzfeldt-Jakob disease)
Lewy body variant of AD AD and dementia with Lewy
bodies
Vascular dementiasMulti-infarct dementia
AD
As of 2017, an estimated 5.5 million Americans –that’s one patient every 66 seconds – have Alzheimer’s disease (AD), including:
1 in 10 people age 65 and over
1 in 3 people age 85 and over
By 2050, there could be as many as 14 million people age 65 and older with Alzheimer’s disease, accounting for half (51 percent) of all people 65 and older with Alzheimer’s.
Alzheimer’s disease facts and figures 2017. http://www.alz.org/documents_custom/2017-facts-and-figures.pdf Last Accessed March 2017.
Alzheimer’s disease facts and figures 2017. http://www.alz.org/documents_custom/2017-facts-and-figures.pdf Last Accessed March 2017.
Source: Alzheimer’s Association 2003
Amyloid plaque, is a fragment (peptide) produced as a result of snipping (cleavage) of the much larger amyloidprecursor protein (APP) by enzymes known secretases.
These amyloiddeposits are thought to play a role in the disease.
Querfurth HW, LaFerla FM. Alzheimer’s Disease: Mechanism of Disease. N Engl J Med 2010; 362:329-344.
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Neurofibrillary tangles consist of insoluble twisted fibers that are found inside of the brain's cells.
They primarily consist of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another.
In Alzheimer's disease the tau protein is abnormal and the microtubule structures collapse. The result of this is that nerve cells can’t communicate with one another.
Querfurth HW, LaFerla FM. Alzheimer’s Disease: Mechanism of Disease. N Engl J Med 2010; 362:329-344.
American Psychiatric Association, 2000
Heightened depression
Staekenborg SS, van der Flier WM, van Straaten EC, et al. Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke 2008; 39:317.
Fischer P, Gatterer G, Marterer A, et al. Course characteristics in the differentiation of dementia of the Alzheimer type and multi-infarct dementia. Acta Psychiatr Scand 1990; 81:551.
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Roman GC, Kalaria RN. Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia. Neurobiol Aging. Dec 2006;27(12):1769-85.
Schneider B, Maurer K, Frolich L. [Dementia and suicide]. Fortschr Neurol Psychiatr. Apr 2001;69(4):164-9.
1. Tiraboschi P, Salmon DP, Hansen LA, et al. What best differentiates Lewy body from Alzheimer's disease in early-stage dementia? Brain2006; 129:729.
2. Nagahama Y, Okina T, Suzuki N, Matsuda M. Neural correlates of psychotic symptoms in dementia with Lewy bodies. Brain 2010; 133:557.
3. Van Hilten JJ, et al. Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease. J Neural Transm Park Dis Dement Sect 1993; 5:235–244.
Aarsland D, Cummings JL, Larsen JP. Neuropsychiatric differences between Parkinson's disease with dementia and Alzheimer's disease. Int J Geriatr Psychiatry 2001; 16:184–191.
Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol 2010; 67:996.
Features SDAT PDDNeuropsychological Domains
Memory Storage problems Retrieval deficit
Executive Function Moderate impairment Prominent impairment
Language Changes Prominent Limited
Visuospatial Deficits Milder Prominent
Bradyphrenia Less common Present
Impaired Attention with Fluctuations Uncommon Characteristic
Neurocognitive Features
PD motor features Absent Present
Neuroleptic Sensitivity Uncommon Present
Autonomic Dysfunction Uncommon Common
REM sleep d/o Absent Common 1. Diehl J, Kurz A. Frontotemporal Lobar Dementia dementia: patient characteristics, cognition, and behaviour. Int J Geriatr Psych. 2002;17:914–918.
2. Rascovsky, MA et al. Rate of progression differs in Frontotemporal Lobar Dementia dementia and Alzheimer disease. Neurol 2005;65:397–403
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Powers R. Alcohol-Induced Dementia. Dementia Education and Training Center. 2008. Last accessed online Dec 8, 2001. http://www.alzbrain.org/pdf/handouts/6001.ALCOHOL%20INDUCED%20DEMENTIA.pdf
Powers R. Alcohol-Induced Dementia. Dementia Education and Training Center. 2008. Last accessed online Dec 8, 2001. http://www.alzbrain.org/pdf/handouts/6001.ALCOHOL%20INDUCED%20DEMENTIA.pdf
*Once a patient is on hospice nearly ANY medication can be used as long as it for palliation
Activities of Daily Living
Behavior
Cognition
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The search criteria combined three separate domains:• Condition (disease type)• Intervention
• ChI’s (donepezil; galantamine; rivastigmine; metrifonate; tacrine)• Antipsychotics (haloperidol; thioridazine; thiothixene; chlorpromazine;
clozapine [PDD]; olanzapine; risperidone; quetiapine; aripiprazole)• Antidepressants (sertraline; fluoxetine [activating, long half-life];
citalopram; trazodone [sedating])• escitalopram, mirtazapine [wt gain/sedating], duloxetine, venlafaxine,
desvenlafaxine• Mood stabilizers (valproate and derivatives; carbamazepine)
• lamotrigine, oxcarbazepine• Lithium• Anticonvulsants
• gabapentin, NOT levetiracetam• Benzodiazepines (for phobia or PTSD)• Memantine
• Symptoms• psychological symptoms of dementia, BPSD, neuropsychiatric
symptoms, behavior.
Wang J, Yu JT, Wang, HF et al. Pharmacological treatment of neuropsychiatric symptoms in Alzheimer’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2015;86:101–109.
Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593.
Tricco et al.: Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network metaanalysis. SystRev 2012 1:31.
Wang J, Yu JT, Wang, HF et al. Pharmacological treatment of neuropsychiatric symptoms in Alzheimer’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2015;86:101–109.
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Philippe, R. Understanding and Managing Behavioural Symptoms in Alzheimer's Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18:156-171.
Cummings JL. Use of cholinesterase inhibitors in clinical practice: Evidence-based recommendations. Focus2004;2(2):239-252.
Philippe, R. Understanding and Managing Behavioural Symptoms in Alzheimer's Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18:156-171.
Philippe, R. Understanding and Managing Behavioural Symptoms in Alzheimer's Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18:156-171.
Philippe, R. Understanding and Managing Behavioural Symptoms in Alzheimer's Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18:156-171.
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Gauthier S, Loft H, Cummings J. Improvement in behavioural symptoms in patients with moderate to severe Alzheimer’s disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry 2008; 23: 537–545.
Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2010; 9:969.
Symptom First Line Second LineAgitation in the content of psychosis
Quetiapine 12.5-100mg/d*1
Olanzapine 2.5-10mg/d*Risperidone .25-2.5mg/d*Aripiprazole 2.5-12.5mg/d*
Agitation unresponsive to first/second-line treatment
Divalproex sodium 500-1500mg/d (consider first line for EtOH dementia)**1
Gabapentin2
Agitation in context of depression / Depression
SSRIs SNRIs
Apathy Methylphenidate (2.5-5mg) 1 Lisdexamfetamine (30-50mg/day)2
Anxiety SSRIs, SNRIs, BZDs (rescue)Olanzapine Zydis 2.5-10mg*
Atypical antipsychotics*
Insomnia Trazodone 25-100mg/dBuspirone 15-60mg/d****
Remeron 7.5-15mg qhsMelatonin 1-3mg qhs
*increased mortality and cerebrovascular events **monitor serum levels, CBC (PLTs), LFTs, serum NH3; watch drug-drug interactions*** for acute use only****allow 2-4 wks for response1. Divide doses 2. Dosing is based on renal function
Adapted from: Pacala JT, Sullivan GM, eds. Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine. 8th ed. New York: American Geriatrics Society; 2013.
*Use about ¼ to ½ of the usual starting dose in Geriatrics
PL Detail-Document, Off-Label Use of Atypical Antipsychotics in Adults. Pharmacist’s Letter/Prescriber’s Letter. July 2015.
1. Sultzer DL, Gray KF, Gunay I, Wheatley MV, Mahler ME. Does behavioral improvement with haloperidol or trazodone treatment depend onpsychosis or mood symptoms in patients with dementia? J Am Geriatr Soc 2001;49:1294-300.
2. Jeste DV, Rockwell E, Harris MJ, Lohr JB, Lacro J. Conventional vs. newer antipsychotics in elderly patients. Am J Geriatr Psychiatry 1999;7:70-6.
3. Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia Number Needed to Harm. MDJAMA Psychiatry. 2015;72(5):438-445.
Wooltorton E. Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ 2002;167(11):1269-1270.
Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry. 2015 May;72(5):438-45.
Symptom First Line Second LineAgitation in the content of psychosis
Quetiapine 12.5-100mg/d*1
Olanzapine 2.5-10mg/d*Risperidone .25-2.5mg/d*Aripiprazole 2.5-12.5mg/d*
Agitation unresponsive to first/second-line treatment
Divalproex sodium 500-1500mg/d (consider first line for EtOH dementia)**1
Gabapentin2
Agitation in context of depression / Depression
SSRIs SNRIs
Apathy Methylphenidate (2.5-5mg) 1 Lisdexamfetamine (30-50mg/day)2
Anxiety SSRIs, SNRIs, BZDs (rescue)Olanzapine Zydis 2.5-10mg*
Atypical antipsychotics*
Insomnia Trazodone 25-100mg/dBuspirone 15-60mg/d****
Remeron 7.5-15mg qhsMelatonin 1-3mg qhs
*increased mortality and cerebrovascular events **monitor serum levels, CBC (PLTs), LFTs, serum NH3; watch drug-drug interactions*** for acute use only****allow 2-4 wks for response1. Divide doses 2. Dosing is based on renal function
Adapted from: Pacala JT, Sullivan GM, eds. Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine. 8th ed. New York: American Geriatrics Society; 2013.
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Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry. 2015 May;72(5):438-45.
1. Rayfield A, Thomas CJ, Borovicka MC. Management of behavioral and psychological symptoms of dementia: The role of mood stabilizers. Mental Health Clinician: July 2014-Dignifying dementia: Accepting the limitations of medications, 2014;4(4):177-182.
2. Calabrese JR, Shelton MD, Rapport DJ, et al. Bipolar disorders and the effectiveness of novel anticonvulsants. J. Clin. Psychiatry 2002;63:(Suppl 3), 5-9.
3. Sival RC, Haffmans PM, Jansen PA, Duursma SA, Eikelenboom P. Sodium valproate in the treatment of aggressive behavior in patients with dementia—a randomized placebo controlled clinical trial. Int J Geriatr Psychiatry 2002;17:579-85.
4. Porsteinsson AP, Tariot PN, Jakimovich LJ et al. Valproate therapy for agitation in dementia: open-label extension of a double-blind trial. Am J Geriatr Psychiatry. 2003 Jul-Aug; 11(4):434-40.
5. Tariot PN, Raman R, Jakimovich L et al. Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial. Alzheimer's Disease Cooperative Study, Valproate Nursing Home Study Group. Am J Geriatr Psychiatry. 2005 Nov; 13(11):942-9.
6. Herrmann N, Lanctot K, Myszak M. Effectiveness of gabapentin for the treatment of behavioral disorders in dementia. J Clin Psychopharmacol. 2000;20:90-93.
Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc 2011;59:577–85.
Nelson C. The Role of Stimulants in Late-Life Depression. Am J Psychaitry 172:6;505-507.Practice Guideline for the Treatment of Patients with Major Depressive Disorder, third edition. American Psychiatric Association. Am J Psychiatry. 2010;167 (supplement)(10):1.Rosenberg, P.B. et al. Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial. J. Clin. Psychiatry 2013;74:810–816.
Billoti de Gage S, Moride Y, Ducruet T et al. Benzodiazepine use and risk of Alheimer's disease: case-control study. BMJ 2014;349.
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Adapted from: Pacala JT, Sullivan GM, eds. Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine. 8th ed. New York: American Geriatrics Society; 2013.
Doody, RS, D’Amico S, Cutler, AJ, et al. Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect in Patients with Alzheimer’s Disease/Dementia: PRISM-II. [Poster] 2014 American Neurological Association (ANA) 139th Annual Meeting, October 10-12, 2014, Baltimore, MD.
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Wang LY, Shofer JB, Rohde K et al. Prazosin for the treatment of behavioral symptoms in Alzheimer's disease patients with agitation and aggression. Am J Geriatr Psychiatry 2009;17:174.
Retz W, Rosler M, Sitzmann L, Becker T. Clozapine in treatment of neuropsychiatric diseases in the elderly. [German] Fortschr Neurol Psychiatr1997;65:347-53.
Klein C, Gordon J, Pollak L, Rabey JM. Clozapine in Parkinson’s disease psychosis: 5-year follow-up review. Clin Neuropharmacol 2003;26:8-11.
Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol 2010; 67:996.
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Mehrabian, Albert (1981). Silent Messages: Implicit Communication of Emotions and Attitudes (2nd ed.). Belmont, CA: Wadsworth.
www.aoa.govwww.alz.orgwww.alzheimers.orgwww.parkinson.orgwww.pdf.orgwww.adaparkinson.orgwww.nfcacares.orgwww.nadsa.orgwww.medicare.govwww.ssa.govwww.fpanet.org
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