Sunday March 16 NEUROCOGNITIVE DISORDERS, THE DSM-5, AND INFORMED TREATMENT CHOICES

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1 Sunday March 16 Breakfast Symposium at the AAGP 2014 Annual Meeting The Renaissance Orlando at SeaWorld, Orlando, Florida Room Crystal A-C 7:30 am Breakfast Buffet 8:00 am Symposium 9:30 am Conclusion NEUROCOGNITIVE DISORDERS, THE DSM-5, AND INFORMED TREATMENT CHOICES Provided by the American Association for Geriatric Psychiatry. Supported by an educational grant from Forest Research Institute, Inc., a wholly-owned subsidiary of Forest Laboratories Inc.

2 George T. Grossberg, MD Samuel W. Fordyce Professor Department of Neurology & Psychiatry Department of Anatomy and Neurobiology Department of Internal Medicine Division of Geriatric Medicine, Dementia, Health Aging Saint Louis University School of Medicine St. Louis, MO

3 Reminder Presentation slides and course booklet will be available for download at AAGP2resources

4 Sunday March 16 Breakfast Symposium at the AAGP 2014 Annual Meeting The Renaissance Orlando at SeaWorld, Orlando, Florida Room Crystal A-C 7:30 am Breakfast Buffet 8:00 am Symposium 9:30 am Conclusion NEUROCOGNITIVE DISORDERS, THE DSM-5, AND INFORMED TREATMENT CHOICES Provided by the American Association for Geriatric Psychiatry. Supported by an educational grant from Forest Research Institute, Inc., a wholly-owned subsidiary of Forest Laboratories Inc.

5 George T. Grossberg, MD Samuel W. Fordyce Professor Department of Neurology & Psychiatry Department of Anatomy and Neurobiology Department of Internal Medicine Division of Geriatric Medicine, Dementia, Health Aging Saint Louis University School of Medicine St. Louis, MO

6 George T. Grossberg, MD Disclosures Research/Grants: Accera, Inc.; Avanir Pharmaceuticals, Inc.; Noven Pharmaceuticals, Inc. Consultant: Forest Laboratories, Inc.; Lundbeck; Novartis Corporation; Otsuka Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Company Safety Monitoring Boards: Merck & Co., Inc.; Newron

7 W. Vaughn McCall, MD, MS Case Distinguished University Chair Department of Psychiatry and Health Behavior The Medical College of Georgia Georgia Regents University Augusta, GA

8 W. Vaughn McCall, MD, MS Disclosures Research/Grants: Merck; National Institute of Mental Health (NIMH)

9 Learning Objective 1 Review and apply changes in the DSM-5 as related to a diagnosis of neurocognitive disorders during annual assessments

10 Learning Objective 2 Implement the latest available treatment approaches as part of an individualized treatment plan aligned to the particular stage of Alzheimer s disease including pharmacologic and non-pharmacologic approaches

11 Case Presentation Mr. J. is a 80 year old male He was diagnosed 4 years ago with dementia, Alzheimer s type. At the time of diagnosis, he was started on donepezil 5 mg/d and increased over time to 10 mg/d. His follow up treatment was primarily with his PCP. After consultation with his PCP, Mr. J. reluctantly moved in with his son David and his family, one year ago, because of concerns about him living alone and not being able to care for himself (cooking, driving a car, managing finances).

12 Case Presentation David, his son, requested an appointment with a geriatric psychiatrist because Mr. J. has been more confused lately and quite irritable at times and has gotten into arguments with a neighbor.

13 DSM-5 Terminology: An Update Delirium Major Neurocognitive Disorder Minor Neurocognitive Disorder Replaces DSM-IV Delirium, Dementia and Amnestic and Other Cognitive Disorders Jeste D. DSM-5 Neurocognitive Disorders Work Group American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

14 DSM-5 Cognitive Domains Complex attention Sustained and divided attention, processing speed Executive ability Planning/ decision making Learning and memory Immediate and recent recall, free recall, cued recall and recognition Language Expressive and receptive Visuoconstructionalperceptual activity Construction and visual perception Social cognition Emotions and behavioral regulation Jeste D. DSM-5 Neurocognitive Disorders Work Group American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

15 DSM-5 Delirium Disturbance in attention and awareness Develops over short period of time, and tends to fluctuate in severity during the day An additional cognitive domain disturbance Physiologic consequence of a medical condition, substance intoxication or withdrawal, toxin exposure, or multiple etiologies American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

16 Major Neurocognitive Disorder (A Syndrome) Including What Was Formerly Known as Dementia A. Evidence of significant cognitive decline in one or more cognitive domains 1. Significant cognitive decline noted by patient, informant, or clinician 2. Objective evidence of substantial impaired cognition, preferably by standard neuropsychological testing B. Cognitive deficits interfere with independence in everyday activities C. Cognitive deficits do not occur exclusively in context of delirium American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

17 Major Neurocognitive Disorder Due to Alzheimer s Disease A. Criteria met for major neurocognitive disorder B. Insidious onset and gradual progression of impairment in one or more cognitive domains American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

18 Major Neurocognitive Disorder Due to Alzheimer s Disease (cont d.) C. Criteria met for probable AD: 1. Either: Evidence of a causative AD genetic mutation (< 1% of all AD) 2. Or: All three of the following: - Decline in memory and learning plus at least one other cognitive domain - Steady, gradual decline without extended plateaus - No evidence of mixed etiology American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

19 Major Neurocognitive Disorder Due to Alzheimer s Disease (cont d.) D. Not better explained by cardiovascular disease, another neurodegenerative disorder, or another mental, neurologic, or systemic disorder American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

20 Mild Neurocognitive Disorder Previous referred to as MCI Evidence of modest cognitive decline in one or more cognitive domains Mild cognitive decline noted by individual, caregiver, or provider Modest impairment documented, preferably by standard neuropsychologic testing Cognitive deficits do not interfere with capacity for independence in everyday activities Cognitive deficits do not occur exclusively in context of delirium MCI = mild cognitive impairment American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed

21 Biomarkers in AD Focus shifted to the identification of AD and treatment in the early clinical stages, as well as before cognitive symptoms emerge during the long preclinical stage Neurodegeneration in AD is estimated to start 20 to 30 years before the first clinical symptoms become apparent. An early diagnosis with reliable biomarkers is essential to distinguish between mild AD, and other dementia types Can serve as a guide for treatment Sutphen CL, et al. Biol Psychiatry Sep 5. [Epub ahead of print]. PMID:

22 The Office-Based Assessment of Neurocognitive Disorder A careful history from a family member/reliable informant Quantify cognitive function, e.g., The Mini Mental State Exam (MMSE), The Montreal Cognitive Assessment (MOCA), St Louis University Mental Status Evaluation (SLUMS) ADL screening (Barthel Inventory or Katz ADL Scale) Screening neurological exam Laboratory (CMP(complete metabolic profile), CBC, TSH, B12/ Folate; UA; (RPR, HIV testing, if indicated); some also recommend: Vitamin D level; CRP; homocysteine level. MRI or CT (old stroke, tumor, NPH, frontotemporal atrophy) Complete neuropsychological testing (if available) Repeat cognitive assessment in six-to-twelve months to confirm/ clarify diagnosis, measure disease trajectory Importance of early recognition TSH = thyroid stimulating hormone; CBC = complete blood count; BUN = blood urea nitrogen; LFT = liver function test; CMP = Complete metabolic profile; UA = urinalysis; RPR = Rapid Plasma Reagin; CRP = c-reactive protein; NPH = normal pressure hydrocephalus Weiner MF, Lipton AM. Clinical Manual of Alzheimer Disease and Other Dementias

23 Treatment Approaches

24 Psychosocial Treatment for AD Improve mood and reduce agitation by increasing pleasurable and decreasing aversive activities for patient and caregiver Decrease agitation in long-term care by matching environment to patient s individual characteristics Discuss modifiable risk factors Alzheimer s Association support groups enhance caregiver knowledge and sustain morale Kurz A. Nervenarzt. 2013;84(1): PMID:

25 Psychosocial Treatment for AD Best accomplished in a collaborative care network Psychosocial interventions include: Cognitive and social stimulation, behavioral-oriented therapies, and caregiver support. Other approaches include validation therapy, reminiscence therapy, reality orientation Studies demonstrate: Improved self-care, emotional well-being, and cognitive function as well as a reduction in risk for, or a delay in, nursing home placement. Universally recommended as initial approach for behavioral symptoms of neurocognitive disorders Geldmacher DS, Kerwin DR. Prim Care Companion CNS Disord. 2013;15(4). pii: PCC. 12r Epub 2013 Aug 29. PMID: Grossberg G, Kamat S. Alzheimer's: The Latest Assessment & Treatment Strategies. Jones and Bartlett Publishers, LLC pp

26 Current Treatments For AD Offer Modest Benefits All ChEIs (donepezil, rivastigmine, and galantamine) are approved for mild to moderate AD; donepezil and rivastigmine also is approved for moderate to severe AD in the US Memantine is approved for moderate to severe AD, either alone or in combination with ChEIs, 1 and for mild AD in some countries (e.g., Russia, Mexico) Until recently, the maximum approved doses were donepezil 10 mg/day, rivastigmine 9.5 mg/24h, galantamine 24 mg/day and memantine 20 mg/day 1 These dosages are associated with modest beneficial effects in managing cognitive deterioration in patients with moderate to severe AD 2,3 1. Singh I, Grossberg.GT. Curr Psychiatry 2012; 11 (6): PMID none. 2. Raina P, et al. Ann Intern Med 2008; 148 (5): PMID: Cummings J. New Engl J Med 2004; 351 (1): PMID:

27 FDA-Approved Treatments for AD Drug Maximum daily dose Mechanism of action Tacrine 160 mg/day ChEI Donepezil 10 mg/day ChEI Rivastigmine 12 mg/day ChEI Galantamine 24 mg/day ChEI Memantine Galantamine ER Rivastigmine transdermal system 20 mg/day NMDA receptor antagonist 24 mg/day ChEI 13.3 mg/day ChEI Donepezil mg/day ChEI Memantine XR 28 mg/day NMDA receptor antagonist Indication Mild to moderate AD All stages of AD All stages of AD Mild to moderate AD Moderate to severe AD Mild to moderate AD Mild to moderate AD Moderate to severe AD Moderate to severe AD Common side effects/comments Nausea, vomiting, loss of appetite, diarrhoea. First ChEI to be approved, but rarely used because of associated possible hepatotoxicity Nausea, vomiting, loss of appetite, diarrhoea, sleep disturbance Nausea, vomiting, diarrhoea, weight loss, loss of appetite Nausea, vomiting, diarrhoea, weight loss, loss of appetite Dizziness, headache, constipation, confusion Nausea, vomiting, diarrhoea, weight loss, loss of appetite Nausea, vomiting, diarrhoea, weight loss, loss of appetite Nausea, vomiting, diarrhoea Dizziness, headache, constipation, confusion ER/XR = extended release Singh I, Grossberg GT. Curr Psychiatry 2012; 11 (6): PMID: None.

28 Case Presentation At the first appointment, you meet with Mr. J. and his son, David David explains that his father has gotten worse in the last few months. He keeps thinking that he is back in his previous apartment and keeps misplacing and looking for lost items, such as his watch, keys, remote control. He states that his father seems to be very frustrated with his Alzheimer s disease

29 Mr. J. s History and Medications Mr. J's medical history Knee replacement (15 years ago) Hip replacement (6 years ago) Mild osteoarthritis Medications NSAID (ibuprofen) Donepezil 5 mg/d increased to 10 mg/d over time

30 Mr. J. s MMSE Assessment Mr. J./Total Orientation to time 3/5 Orientation to place 3/5 3-word registration 1/3 Attention and calculation 3/5 Word recall 1/3 Language 4/8 Visuospatial copying 0/1 Total 15/30 MMSE = Mini Mental State Exam

31 Is there a rationale for combination treatment of cholinesterase inhibitor and memantine?

32 Glutamatergic and Cholinergic Pathways Limbic system Nucleus basalis Neocortical assoc. areas Glutamatergic Cholinergic Ent. cortex Dentate gyrus CA3 CA1 Septum Subiculum Parsons CG, et al. Neurotox Res. 2013;24(3): PMID:

33 Memantine Alone and in Combination with Donepezil Significantly Improved Spatial Memory Acquisition Memory acquisition Young 3xTg-AD mice (6 months of age) Latency, mean ± SEM [s] # * # # # # * * * N = 30 *p < 0.05, memantine-donepezil vs sucrose; #p < 0.05, memantine vs sucrose Day Martinez-Coria H, et al. Poster presented at ECNP, % Sucrose Donepezil 1 mg/kg/day Memantine 30 mg/kg/day Memantine + donepezil

34 Combination Therapy for Alzheimer's Disease Review of combination studies in mild-tomoderate and moderate-to-severe AD by Patel and Grossberg demonstrated: Combination therapy (CT) with cholinesterase inhibiters (donepezil, galantamine, rivastigmine) plus memantine showed better outcomes than for placebo add-on with respect to measures of cognition, daily function, behavior and global outcome The strongest evidence supporting the superiority of CT over ChEI monotherapy derives from a 24-week pivotal phase III clinical trial of addition of memantine to chronically stable donepezil treatment in highly selected subjects with moderate to severe AD Patel L, Grossberg GT. Drugs Aging. 2011;28(7): PMID:

35 Clinical Benefits of Combination Therapy 4 Severe Impairment Battery (SIB) Mean change from baseline Memantine combination therapy Placebo + donepezil -4 Baseline Study week N = 404 *p <.05; **p <.01; ***p <.001 vs. placebo + donepezil Tariot PN, et al. JAMA. 2004; 291 (3): PMID: Endpoint (LOCF) Improvement Worsening

36 Memantine Combination Therapy Benefits Function Mean change from baseline N = Activities of Daily Living inventory (ADCS-ADL 19 ) Memantine combination therapy Donepezil monotherapy -4 Baseline Study week *p <.05 vs. donepezil monotherapy Tariot PN, et al. JAMA. 2004; 291 (3): PMID: Endpoint (LOCF) Improvement Worsening

37 Most Frequent Adverse Events* (%) Total patients with AEs Discontinuations due to AEs Agitation Confusion Fall Influenza-like symptoms Dizziness Headache Urinary tract infection Urinary incontinence Accidental injury Upper respiratory tract infection Peripheral oedema Diarrhoea Faecal incontinence Combination (n = 202) Fewer 9.4 patients receiving combination 11.9therapy discontinued 7.9 due to AEs 2.0 Agitation possibly ameliorated with combination Confusion was therapy more common in patients receiving 7.4 combination therapy, but this 6.5 did not lead 6.9to more discontinuations Gastrointestinal 5.0 AEs possibly ameliorated 6.5 by memantine 5.0 combination therapy *Occurring in 5% of patients in either treatment group Tariot PN, et al. JAMA 2004; 291 (3): PMID:

38 Combination Therapy Superior to Monotherapy in Key Domains in Moderate AD (MMSE 10 19) p =.008 p =.008 p =.04 SMD (95% CI) Favours combination therapy Cognition Global Function Favours donepezil monotherapy Two 6-month, placebo-controlled studies Patients received either memantine combo therapy or donepezil alone N = 367 (186 memantine + donepezil 10 mg/ day; 181 donepezil 10 mg/day monotherapy) Atri A, et al. Alz Res Therapy. 2013; 5 (1): 6. PMID: None.

39 Patients Are Less Likely to Get Worse if Taking Combination Therapy in Comparison with Donepezil Alone Moderate to severe AD 8.7 p < Combination therapy Donepezil monotherapy Moderate AD 5.9 p < Patients with marked clinical worsening (%) Marked clinical worsening defined as a decline of 4 points on ADAS-Cog or 5 points on SIB, plus any decline on ADCS-ADL 19/23 and CIBIC-Plus Atri A, et al. Alz Res Therapy. 2013; 5 (1):6. PMID: None.

40 High-Dose Donepezil, Rivastigmine or Memantine: Is it the Next Step in AD Treatment? Recently, the FDA approved higher daily doses of rivastigmine TDS (13.3 mg/24h) for mild to moderate and severe AD 1 and donepezil (23 mg) and memantine (28 mg) for moderate to severe AD, on the basis of positive Phase III trial results 2-4 Studies have reported that combining a ChEI with memantine is well tolerated and may result in synergistic benefits by affecting different neurotransmitters in patients with moderate to severe AD 5,6 TDS = Transdermal system 1. Cummings J, et al. Dement Geriatr Cogn Disord. 2012;33(5): PMID: Farlow MR, et al. Clin Ther 2010;32 (7): ; PMID: Periclou & Hu. Poster presented at 11th ICAD. 2008; Chicago, USA 4. Grossberg GT, et al. CNS Drugs Jun;27(6): PMID: Tariot PN, et al. JAMA. 2004; 291 (3): PMID: Xiong G, et al. Geriatrics. 2005; 60 (6): PMID:

41 At Week 24, the Change in SIB Score was Significantly Greater with Donepezil 23 mg/day vs. 10 mg/day Least squares mean change from baseline in SIB total score (SE) Donepezil 23 mg/day, n Donepezil 10 mg/day, n * Study Week (OC) (LOCF) *** ** *** *** Baseline Donepezil 23 mg/day Donepezil 10 mg/day Clinical improvement Clinical decline In the OC population, the change in SIB score from baseline was significantly greater with donepezil 23 mg/day at Weeks 6 (p < 0.05), 12 (p < 0.001), 18 (p < 0.01), and 24 (p < 0.001) In both subgroups of patients concurrently taking and not taking memantine, the change in SIB score from baseline was significantly greater with donepezil 23 mg/day (p = and p= 0.007, respectively, vs 10 mg) *p < 0.05, **p < 0.01, ***p < between treatment groups; OC and ITT, LOCF population: SE =standard error; OC = observed cases; ITT =I ntent-to-treat; LOCF = last observation carried forward Farlow MR, et al. Clin Ther 2010; 32 (7): PMID:

42 Conclusions of the Farlow 2010 Study In patients with moderate to severe AD who were receiving a stable dose of donepezil 10 mg/day, donepezil 23 mg/day provided significantly greater cognitive benefit as measured using SIB Although no significantly greater effect on global functioning as measured by CIBIC-Plus was found with the dose increase, post hoc analyses suggested that more severely cognitively impaired patients (according to SIB) may experience a global benefit with an increase to the higher donepezil dose CIBIC = Clinicians Global Impression of Change Farlow MR, et al. Clin Ther. 2010; 32 (7): PMID:

43 Treatment with Memantine XR Significantly More Effective After 24 weeks vs. Placebo on Outcomes of Behaviour and Verbal Fluency Outcome Measure n Baseline a change from baseline Endpoint LMSD (95% CI) p value SIB Memantine/ChEI Placebo/ChEI ± ± ± ± (1.0, 4.2).001 CIBIC-Plus b Memantine/ChEI Placebo/ChEI N/A N/A 3.8 ± ± 1.2 N/A.008 ADCS-ADL 19 Memantine/ChEI Placebo/ChEI ± ± ± ± (-0.3, 1.8).177 NPI Memantine/ChEI Placebo/ChEI ± ± ± ± (-4.5, -0.8).005 Verbal fluency Memantine/ChEI Placebo/ChEI ± ± ± ± (0.2, 0.9).004 Week 24, LOCF; ITT population; CI =confidence interval; a Mean ± SD; b The CIBIC-Plus is a rating of change from baseline, thus, baseline scores are not applicable Grossberg GT, et al. CNS Drugs Jun;27(6): PMID:

44 Conclusions of a Phase III Study Memantine XR (28 mg), administered once-daily, is an effective and safe treatment for patients with moderate to severe AD, maintained on stable ChEI therapy Memantine XR, in combination with ChEI, provides significant benefits over placebo/chei on measures of: Cognition Global status Behavior Verbal fluency No data available comparing memantine XR 28 mg/d versus memantine 10mg bid N = 677 Grossberg GT, et al. CNS Drugs Jun;27(6): PMID:

45 Higher-Dose Rivastigmine Patch in Mild to Moderate Alzheimer s Disease 48-week, double-blind study in patients with mild-to-moderate AD ADAS-IADL and ADAS-Cog scored favored the 13.3 mg/24h patch The 13.3 mg/24h patch was statistically superior to the 9.5 mg/24h patch on the ADAS-IADL scale N= 207 N= 203 N= 207 N= 203 * p < 0.05, ** p < for 13.3 mg/24 h vs. 9.5 mg/24 h rivastigmine patch. ADAS-IADL = Instrumental Activities of Daily Living domain of the Alzheimer s Disease Cooperative Study Activities of Daily Living ADAS-Cog = Alzheimer s Disease Assessment Scale cognitive subscale Cummings J, et al. Dement Geriatr Cogn Disord. 2012;33(5): PMID:

46 Higher-Dose Rivastigmine Patch in Severe Alzheimer s Disease 24-week, double-blind, prospective, randomized study in patients with severe AD SIB score significantly favored the 13.3 mg/24h patch **P < versus 4.6 mg/24 h patch N = 356 N = 360 Farlow MR, Grossberg GT, et al. CNS Neurosci Ther Oct; 19(10) PMID:

47 Case of Mr. J. Mr. J. s dose of donepezil was increased to 23mg/d; dose of memantine XR was titrated slowly from 7mg/d to memantine XR 28 mg/d Over the next 6 months, there is no improvement in Mr. J.'s symptoms, his condition does not deteriorate. His agitation has diminished to minor frustration. Over the next year, Mr. J. s symptoms increased, with difficulty with personal hygiene, coordination and need for additional supervision

48 The Art of Sharing the Diagnosis of with Patients and Families When discussing results, include family members or others providing care Find a private/quiet location and schedule ample time for the visit Find out about their concerns and understanding of the disease and meaning of tests Explain findings, implications and limitations of results Address concerns about prognosis, expectations, and treatment options Grossberg GT, et al. Prim Care Companion J Clin Psychiatry. 2010;12:PCC. 09cs PMID:

49 Managing the Patient and Caregivers Discussing the clinical diagnosis of AD should be a process rather than an event and can best be accomplished over the course of several visits Ensure that the patient and caregivers understand that there is a problem that can be addressed by medical treatment and that will require additional resources to manage appropriately Grossberg GT, et al. Prim Care Companion J Clin Psychiatry. 2010;12(1):PCC. 09cs PMID:

50 Managing the Patient and Caregivers (cont d) Manage any misconceptions or myths the patient or family may have about AD Provide information about available resources and support organizations Encourage active life-style and socialization Discuss caregiver stresses Grossberg GT, et al. Prim Care Companion J Clin Psychiatry. 2010;12(1):PCC. 09cs PMID:

51 Clinical Connections Diagnosis of neurocognitive disorders can be guided by new diagnostic language in DSM-5 and when appropriate, by imaging or biomarkers Major and mild neurocognitive disorders exist on a spectrum of cognitive and functional impairment. Major neurocognitive disorders corresponds to the condition referred to in DSM-IV as dementia. Neuropsychological testing, with performance compared with norms appropriate to the patient's age, educational attainment, and cultural background, ideally is part of the standard evaluation of neurocognitive disorders and is particularly critical in the evaluation of mild neurocognitive disorders. If neuropsychological testing is unavailable, a variety of brief office-based or "bedside" assessments are available.

52 Clinical Connections (cont d.) Initiate an ongoing dialogue with patients and family/caregivers to educate them about neurocognitive disorders, modifiable risk factors and discuss quality of life issues Implement psychosocial interventions whenever possible

53 Clinical Connections (Cont d) There are few FDA-approved treatments for AD 1 Higher doses of agents have been approved and may be an option for patients who have maxed out on their AD therapy, or no longer respond to lower doses Donepezil (23 mg/day) 2 Rivastigmine TDS (13.3mg/24 hrs) 3 Memantine XR (28 mg/day) 2 Once-daily formulations can improve adherence Combining a ChEI with memantine is associated with slower cognitive decline and clinical benefits. 4 Therefore, it may be beneficial to assess the safety, tolerability, and efficacy of combination with higher doses of donepezil and memantine XR 1 1. Singh I, Grossberg GT. Curr Psychiatry 2012;11(6):20 29.PMID:None 2. Farlow MR, et al. Clin Ther 2010; 32 (7): PMID: Cummings J, et al. Dement Geriatr Cogn Disord. 2012;33(5): PMID: Atri A, et al. Alzheimer Dis Assoc Disord 2008; 22 (3): PMID:

54 Questions & Answers

55 Reminder Presentation slides and course booklet will be available for download at AAGP2resources

56 Reminder Evaluate this symposium online at