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

Dementia Defined Decline in cognitive function from baseline

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 p.1079; Gauthier S et al. Lancet :

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

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

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

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.

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

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

Dementia Drugs

Dementia Drugs Card Sort

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

Efficacy Rogers: Neurology,

Trinh NH et al. JAMA Jan 8;289(2):

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

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

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

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 Mar 8; 366(10):

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

Dementia and End of Life Issues