2012 Medical School for Actuaries Nov. 6-7, 2012 Session #1: Alzheimer s Disease

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1 2012 Medical School for Actuaries Nov. 6-7, 2012 Session #1: Alzheimer s Disease Dylan Wint, M.D.

2 ALZHEIMER DISEASE Dylan Wint, M.D. Lou Ruvo Center for Brain Health DEFINITIONS Cognitive related to thinking, memory, judgment, perception Dementia acquired cognitive disorder with dysfunction in ADLs or IADLs ADL hygiene, ambulation, toileting eating, dressing IADL shopping, housekeeping, accounting, food/meds, technology 1

3 ALZHEIMER DISEASE MOST COMMON DEMENTIA 5.5 MILLION PEOPLE IN U.S. 1 NEW CASE EVERY 70 SECONDS 7.8 MILLION AMERICANS BY 2030 $172 BILLION ANNUALLY IN U.S. 35 MILLION PEOPLE WORLDWIDE NOT THE ONLY CAUSE OF DEMENTIA INCREASES WITH AGE % of Population With Dementia Prevalence (%) Age 2

4 COSTS RISING $ BILLIONS Alzheimer s Assn. Changing the Trajectory of AD, 2010 Cognitive SYMPTOMS Inability to learn/remember Spatial navigation problems Difficulty with planning Behavioral Irritability Apathy Depression Delusions 3

5 BRAIN ATROPHY Barrow Neurological Institute PLAQUES AND TANGLES PLAQUES Beta-amyloid Extracellular TANGLES Phospho-tau Intracellular Microscope view 4

6 AD: A LIFE-LONG PROCESS Education Exercise Brain fitness Antioxidant diet Heart health AD Less Likely AD More Likely Female sex E4 genotype Hypertension Diabetes Head trauma Smoking DEMENTIA: TIP OF THE AD ICEBERG Disability Death Cognitive and behavioral changes Brain shrinkage and dysfunction Protein accumulation, inflammation Researchgoddess.com Aging Genetics Lifestyle 5

7 DIAGNOSIS Obvious disease Disability Death Cognitive testing Cognitive and behavioral changes Brain imaging Brain shrinkage and dysfunction Brain biopsy Spinal fluid Brain imaging Protein accumulation DIAGNOSIS Obvious disease Cognitive testing Disability Death Cognitive and behavioral changes Brain imaging Brain shrinkage and dysfunction Brain biopsy Spinal fluid Brain imaging Protein accumulation 6

8 COGNITIVE TESTING Screening tests Brief (10-15 mins) Can be done by anyone Wide variety MMSE, MoCA, others Formal neuropsychological testing Usually a few hours Requires formal training Spotty insurance coverage SCREENING TESTS MoCA 7

9 SCREENING TESTS MoCA NEUROPSYCHOLOGICAL TESTING Rey-Osterreith Complex Figure 8

10 NEUROPSYCHOLOGICAL TESTING Boston Naming Test NEUROPSYCHOLOGICAL TESTING More sensitive than screening Detects disease that screening misses More specific than screening Can distinguish between different dementias Can detect other causes of cognitive change (malingering, depression, medication effects) 9

11 COGNITIVE TESTING Testing may need to be repeated Demonstrate progression Demonstrate stability Clarify findings New information DIAGNOSIS Obvious disease Disability Death Cognitive testing Cognitive and behavioral changes Brain imaging Brain shrinkage and dysfunction Brain biopsy Spinal fluid Brain imaging Protein accumulation 10

12 BRAIN IMAGING COMPUTERIZED AXIAL TOMOGRAPHY (CAT) Exclude other problems Large stroke Large tumor Advanced cases of dementia Poor at detecting AD characteristics Fast, cheap Mainly used if MRI unavailable BRAIN IMAGING MAGNETIC RESONANCE IMAGING (MRI) ADVANTAGES High resolution Small strokes Tumors Other dementias (vascular, FTD) Can detect AD characteristics Atrophy of hippocampus Parietal and temporal lobe atrophy 11

13 BRAIN IMAGING MAGNETIC RESONANCE IMAGING (MRI) DISADVANTAGES Cannot be used with pacemaker Long, loud Patient must stay still Claustrophobia-inducing MR IMAGES IN AD Hippocampus NORMAL ALZHEIMER Florida Alzheimer s Disease Research Center 12

14 BRAIN IMAGING POSITRON EMISSION TOMOGRAPHY (PET) Measures brain metabolism Characteristic pattern in AD Sensitive to change FDG-PET IMAGES IN AD HEALTHY AGING ALZHEIMER DISEASE MGHRadRounds.org 13

15 DIAGNOSIS Obvious disease Disability Death Cognitive testing Cognitive and behavioral changes Brain imaging Brain shrinkage and dysfunction Brain biopsy Spinal fluid Brain imaging Protein accumulation PROTEIN ACCUMULATION DeMeyer et al 2010 =Proven Alzheimer dementia 14

16 PROTEIN ACCUMULATION = Mild cognitive impairment, later developed dementia DeMeyer et al 2010 PROTEIN ACCUMULATION CEREBROSPINAL FLUID ANALYSIS ADVANTAGES Highly sensitive for AD Extremely specific for AD Early detection Measures physiologic processes DISADVANTAGES Only performed at reference labs Requires cerebrospinal fluid 15

17 PROTEIN ACCUMULATION SleepandNeurology.blogspot.com PROTEIN ACCUMULATION Amyloid Imaging Alzheimer dementia Normal cognition Normal cognition 16

18 PROTEIN ACCUMULATION AMYLOID PET SCAN ADVANTAGES PET scanners widely available Non-invasive (IV) Reflects physiologic process DISADVANTAGES Expensive Not completely predictive GENE TESTING Most AD is not genetic ApoE ε4 largest genetic influence 50-65% of AD patients carry ε4 3rare mutations (APP, PS1, PS2) 3% of all cases of AD Most are early onset (mid 50 s) 17

19 TREATMENT Treatments slow descent into disability Treatments beneficial even in late disease Behavioral symptoms must be addressed COGNITIVE TREATMENTS Cholinesterase inhibitors Tacrine (COGNEX) Donepezil (ARICEPT) Galantamine (RAZADYNE) Rivastigmine (EXELON) Glutamate antagonist Memantine (NAMENDA) Combine with cholinesterase inhibitors 18

20 COGNITIVE TREATMENT Slows Decline p= p< Improve CIBIC-plus Score p= Donepezil Placebo Weeks p< p= p< Decline Donepezil n= Placebo n= COGNITIVE TREATMENT Delays Placement Probability of Remaining at Home < 80 mg/day mg/day mg/day Days Knopman et al, Neurology,

21 BEHAVIORAL SYMPTOMS Mild Mod Sev Depression Agitation Anxiety Delusions Halluc BEHAVIORAL SYMPTOMS Hasten NH Placement 2000 Days to Placement Without Behaviors With Behaviors Phillips VL, Diwan S. JAGS 2003; 51:188 20

22 BEHAVIORAL SYMPTOMS Increase Cost of Care $US per year Indirect Direct Low Behavioral Symptoms High Behavioral Symptoms NPI: Neuropsychiatric Inventory Murman DL, et al. Neurology 2002; 59:1721 BEHAVIORAL TREATMENTS Agitation and aggression Antipsychotics Anti-adrenergic Antidepressants Environment Depression and anxiety Antidepressants Nonpharmacologic 21

23 BEHAVIORAL TREATMENTS Delusions and hallucinations Antipsychotics Environment Sleep disturbance Nonpharmacologic Melatonin Sedating antidepressants 22

24 COMBINATION TREATMENT Preserves Cognition Donepezil + Memantine Donepezil + Placebo Memantine + Placebo Placebo + Placebo MMSE Moderate to Severe AD, n=295 Mean MMSE= 9.1 ± % MMSE % MMSE Treated with donepezil 85% > 1 year 55% > 3 years Week Howard et al NEJM 2012 COMBINATION TREATMENT Preserves Function Donepezil + Memantine Donepezil + Placebo Memantine + Placebo Placebo + Placebo BADLS Moderate to Severe AD, n=295 Mean MMSE= 9.1 ± % MMSE % MMSE Treated with donepezil 85% > 1 year 55% > 3 years Visit Week Howard et al NEJM

25 CHOLINESTERASE INHIBITORS Donepezil (Aricept) Mild, moderate, severe AD 5, 10 mg daily tabs 5, 10 mg oral disintegrating tabs 23 mg XR tab Rivastigmine (Exelon) Mild, moderate AD or Parkinson dementia 1.5, 3, 4.5, 6 mg BID tabs 2 mg/ml liquid 4.6 mg, 9.5 mg daily patch Galantamine (Razadyne + generic) Mild, moderate AD 4, 8, 12 mg BID tabs 4mg/100 ml liquid 8,16, 24 mg daily SR cap 24

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