1. CAROLINE HARADA, M.D. ASSOCIATE PROFESSOR OF MEDICINE UAB DIVISION OF GERONTOLOGY, GERIATRICS, AND PALLIATIVE CARE NOVEMBER 2013 Dementia

2. Dementia Defined Decline in cognitive function from baseline

3. Epidemiology Dementia in the US population  Over 65: 5-10%  Over 85: 30-50% Kennedy, GJ. Geriatric Medicine, 4 th Ed. Cassel et al, Eds. 2003. p.1079; Gauthier S et al. Lancet 2006. 376: 1262-1270.

4. DSM-5: Major Neurocognitive Disorder DSM-5: Major Neurocognitive Disorder Decline from prior level of performance in at least 1 cognitive domain: 1. Complex attention 2. Executive function 3. Learning and memory 4. Language 5. Perceptual-motor 6. Social cognition Based on history and quantified clinical assessment Interfering with independence in everyday activities Not exclusively with delirium, psychiatric disorders Diagnostic and Statistical Manual of Mental Disorders, 5 th Ed, 2013

5. Dementia types Alzheimer Disease Mixed Vascular DLB Other 60% 15-20% 5-10% 5%

6. Alzheimer Disease New diagnostic criteria published in 2011 New diagnostic criteria published in 2011  Clinical criteria  Insidious onset of months to years  Progression of cognitive decline  Amnestic or nonamnestic symptoms  Differential diagnosis of Alzheimer dementia  Biomarkers  Accumulation of amyloid beta  Neuronal injury

7. Vascular Dementia Due to large or small vessel disease Stepwise progression of symptoms Executive function and processing speed can decline first, followed by memory, language, etc.

8. Dementia with Lewy Bodies Characteristics  Prominent visual hallucinations  Parkinsonism (gait, balance, rigidity, bradykinesia- rest tremor less common)  Falls or gait difficulties  Fluctuations in cognition  Sensitivity to antipsychotics (extrapyramidal side effects) Also  REM sleep behavior disorder  Decreased sympathetic function Knopman DS. Mayo Clin Proc, 2006; Blass DM, Rabins PV. Annals Int Med, 2008

9. Clinical Evaluation History Physical Examination  Vascular disease  Neurological exam Laboratories  B12, TSH, RPR, HIV, Vit D Imaging  Brain CT or MRI Neuropsychological testing

10. Dementia Drugs

11. Dementia Drugs Card Sort

12. Acetylcholinesterase Inhibitors Donepezil (Aricept) Galantamine (Razadyne) Rivastigmine (Exelon)

13. Efficacy Rogers: Neurology, 1998.136-145

14. Trinh NH et al. JAMA. 2003 Jan 8;289(2):210- 6.

15. Statistically significant? Yes. Clinically significant? Maybe? Adverse effects: nausea, vomiting, diarrhea, dizziness, tremor, and bradycardia Efficacy: Cholinesterase Inhibitors Raina, P et al. Ann Intern Med. 2008

16. NMDA antagonist: Memantine (Namenda) Mechanism of action: inhibition of glutamate Randomized, placebo-controlled trials show similarly small (but statistically significant) benefits Reisberg B et al. NEJM 2003; Raina, P et al. Ann Intern Med. 2008

17. NMDA antagonist Memantine (Namenda) Reisberg B et al. NEJM 2003

18. FDA-approved only for moderate to severe dementia Adverse effects: minimal Benefit to combination therapy with cholinesterase inhibitors: unclear Howard R et al, N Engl J Med. 2012 Mar 8; 366(10):893-903

19. Drug candidates that to date have no proven efficacy Anti-inflammatories Statins Estrogen Antioxidants Gingko biloba Fish oil, omega-3 fatty acids Vitamin E Lowering homocysteine Alcohol, especially wine Huperzine Curcumin Nicotine Insulin & insulin sensitizers, ketones

20. Dementia and End of Life Issues