AOA/ACOFP 113th Annual Convention and Scientific Seminar Las Vegas, Nevada Alzheimer's Disease Brain Failure, Stopping the Momentum Katherine E. Galluzzi, DO, CMD, FACOFP dist. Monday, October 27, 2008 9:00-11:00am CME/CEU Information The American College of Osteopathic Family Physicians is accredited by the American Osteopathic Association Council to sponsor continuing medical education for osteopathic physicians. The American College of Osteopathic Family Physicians designates the lectures and workshops for Category 1A credit on an hour-for hour basis, pending approval by the AOA CCME. ACOFP is not responsible for the content.
DISCLOSURE OF FINANCIAL RELATIONSHIPS WITHIN 12 MONTHS OF DATE OF THIS FORM Speaker Name: Katherine E. Galluzzi, DO, CMD, FACOFP dist Have you, or any of your immediate family, had a financial relationship or interest with any proprietary entity producing health care goods or services within the past 12 months? Yes If you answered Yes to the question above, please indicate the relationship(s): Relationships: Speakers' Bureau* If other: Organization/Clinical Area Involved: Pfizer/Eisai - Alzheimer's Disease *If you checked Speakers Bureaus: Did you participate in company-provided speaker training related to your proposed topic? No Did you travel to participate in this training? No Did the company provide you with slides of the presentation in which you were trained as a speaker? No Did the company pay the travel/lodging/other expenses? No Did you receive an honorarium or consulting fee for participating in this training? No Have you received any other type of compensation from the company? Please specify: No When serving as faculty for ACOFP, will you use slides provided by a proprietary entity for your presentation/handout materials? Will your topic involve information or data obtained from commercial speaker training? DISCLOSURE OF UNLABELED/INVESTIGATIONAL USES OF PRODUCTS Will the content of your material(s)/presentation(s) in this CME activity include discussion of unapproved or investigational uses of products or devices? Will touch on emergent therapeutic area of vaccination against B-amyloid. I have read the ACOFP policy on full disclosure. If I have indicated a financial relationship or interest, I understand that this information will be reviewed to determine whether a conflict of interest may exist, and I may be asked to provide additional information. I understand that failure or refusal to disclose, false disclosure, or inability to resolve conflicts will require the ACOFP to identify a replacement.
What is your age? Mild Cognitive Impairment: What s in Your Cranium? Katherine E. Galluzzi, D.O., CMD, FACOFP dist. Professor and Chair Department of Geriatrics Philadelphia College of Osteopathic Medicine 1. 20 35 2. 36 50 3. 51 65 4. 66 75 5. I d rather not say What is your gender? 1. male 2. female Are you being treated for hypertension? 1. yes 2. no 1
Are you being treated for hyperlipidemia? 1. yes 2. no How do you rate your memory? 1. excellent 2. very good 3. fair 4. poor 5. I d rather not say Dementia COGNITIVE CONTINUUM Normal Mild Cognitive Impairment Dementia A clinical syndrome having major impact on an aging individual Alzheimer s Disease Parkinson s Disease Dementia with Lewy Bodies Vascular Dementia 2
Dementia of Alzheimer Type Neurodegenerative process that results in cognitive deficits which cause significant decline in social or occupational functioning and represent a substantial decline in previous level of functioning Other causes are not responsible for the deficits The deficits do not occur exclusively during delirium Mild Cognitive Impairment Transitional state between the cognitive changes of normal aging and the fully developed features of dementia Peterson, RC. Seminars in Neurology 2001;27(1):22-31 Original Criteria Memory complaint, preferably qualified by an informant Memory impairment for age and education Preserved general cognitive function Intact activities of daily living Not demented Adapted from Reisberg B et al. Am J Psychiatry 1982;139:1136-1139 Cognitive complaint Not normal for age, not demented Cognitive decline, essentially normal ADL s YES MCI NO Amnestic MCI Memory impaired? Non-amnestic MCI Memory Single non-memory YES Impairment NO YES cognitive domain NO only? Impairment? Amnestic MCI Single domain Amnestic MCI Multiple domains Non-amnestic MCI Single domain Petersen RC. J Intern Med 2004;256:183-194. Non-amnestic MCI Multiple domains M C I D E M E N T I A DEGENERATIVE VASCULAR OTHER Alzheimer s disease Frontotemporal dementia Dementia w/ Lewy Bodies Vascular dementia; vascular cognitive impairment Neoplasm Metabolic Psychiatric Normal pressure hydrocephalus NOS Peterson RC, O Brien J. J Geriatric Psychiatry Neurol 2006;19:147-154 3
Modified from: Brumback RA, Leech RW: Alzheimer's Disease: Pathophysiology and the hope for therapy. Journal of the Oklahoma State Medical Association. 1994; 87:103-111. Dementia Evaluation Routine Mental Status Examination evaluates: level of consciousness orientation attention visuo-spatial skills mood/personality Folstein Mini Mental State Exam: www.carstensfreeforms.com Clock Drawing test Why is early identification important? 1. cure is possible 2. medications to slow progression are available 3. there is a therapeutic window of efficacy for treatment 4. identification allows for anticipatory guidance 5. it isn t 4
> 67% of individuals are moderately demented at the time of diagnosis! Gifford DR & Cummings JL1999 Neurology;52:224-227 Measures to Predict Progression to AD Cognitive Domains Amnestic Mild Cognitive Impairment Subtype Apolipoprotein E4 (ApoE4): carrier status in several studies was shown to be a risk factor 1 Inability to benefit from semantic clues may indicate more rapid progression 2 Structural Neuroimaging: studies suggest that atrophy of hippocampal formation predicts the rate of progression from MCI to AD 3 Memory Executive function Visual spatial perception Verbal functioning Attention Information processing speed Motor skills Executive functioning 1. Aggarwal NT et al. Neurocase2005;11:3-7; Peterson RC et al. Ann NY AcadSci1996;802:58-69 2. Dubois B, Albert ML. Lancet Neurol 2004;3:246-248 3. Jack CR, Petersen et al. Neurology 1999;52:1397-1403; Jack CR et al. Neurology 2005;65:1227-1231 5
Verbal Memory Forming new associations between items is critical for establishing episodic memory 10 pairs of words to study followed by a recognition test Tests immediate recognition memory and delayed recognition memory Adapted from Mindstreams TM Cognitive Health Assessment Version 2.1 NeuroTrax Corporation 2003 dish - bird dog - candle pillow - key tree - icicle deer - rug cat - lamp lake - plug date - rug piano - pinecone bottle - chair lake 1. house 2. plug 3. jeep 4. soup Non-verbal Memory Better predictor of early AD than verbal tests (Kawas, Corrada et al 2003) Immediate recognition, delayed recognition memory Eight simple geometric patterns note their orientation Recognition test consists of four possible alternatives Adapted from Mindstreams TM Cognitive Health Assessment Version 2.1 NeuroTrax Corporation 2003 6
1. 2. 3. 4. 1. 2. 3. 4. 7
Visual Spatial Imagery Test Assesses abstract spatial ability Computer-generated everyday scene containing a red pillar (rectangle) Four views of the scene are presented at the bottom of the screen Which of the four views corresponds to the view of the scene from the location of the pillar? Adapted from Mindstreams TM Cognitive Health Assessment Version 2.1 NeuroTrax Corporation 2003 1. 2. 3. 4. Stroop Interference Well-established cognitive test (MacLeod, 1991) Measures facility with which an individual can shift perceptual set to conform to changing demands Shown to discriminate among brain-damaged individuals, those with schizophrenia, Parkinson s and Huntington s disease Interference effect is greater for those with frontal lobe damage than for other groups cat 8
red 1. 2. red 1. 2. 9
Verbal Rhyming Impairment in verbal fluency is a telltale sign of dementia Test assesses higher-order verbal skill Which word rhymes with the object presented Language skills, semantic knowledge 1. 2. Adapted from Mindstreams TM Cognitive Health Assessment Version 2.1 NeuroTrax Corporation 2003 1. ring 2. art 3. spoon 4. gold 1. choose 2. pin 3. bench 4. rabbit 10
Verbal Naming Assesses basic verbal skills Language skills, semantic knowledge Adapted from Mindstreams TM Cognitive Health Assessment Version 2.1 NeuroTrax Corporation 2003 1. ring 2. shell 3. heart 4. gold CERAD * Word Battery 1. piano 2. pinecone 3. wrench 4. winch dream score bowl pillow bell game snow peacock rice harmonica * Consortium for Establishing A Registry for Alzheimer Disease 11
Mild Cognitive Impairment Clinical Trials Sponsor Compound n Duration (yr) Primary Outcome Rate of Prog (%) Result ADCS Donepezil Vitamin E 769 3 AD 16 Partially positive Novartis Rivastigmine 1018 3-4 AD 9 Negative J & J 2 trials Galantamine 2048 2 CDR 5 Negative Merck Rofecoxib 1457 3-4 AD 5 Negative Adapted from Peterson RC. Semin Neurol 2007; 27(1):22-31 How do you rate your memory now? 1. excellent 2. very good 3. fair 4. poor 5. I d rather not say 12