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Dementia. Caroline Harada, M.D. Associate Professor of Medicine UAB Division of Gerontology, Geriatrics, and Palliative Care November 2013. Dementia Defined. Decline in cognitive function from baseline. Epidemiology. Dementia in the US population Over 65: 5-10% Over 85: 30-50%.
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Dementia Caroline Harada, M.D. Associate Professor of Medicine UAB Division of Gerontology, Geriatrics, and Palliative Care November 2013
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, 4th Ed. Cassel et al, Eds. 2003. p.1079; Gauthier S et al. Lancet 2006. 376: 1262-1270.
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, 5th Ed, 2013
Dementia types 5% Other 5-10% DLB 5-10% Vascular 15-20% Mixed 60% Alzheimer Disease
Alzheimer Disease • 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 ClinProc, 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
Acetylcholinesterase Inhibitors • Donepezil (Aricept) • Galantamine (Razadyne) • Rivastigmine (Exelon)
Efficacy Rogers: Neurology, 1998.136-145
Efficacy: Cholinesterase Inhibitors Statistically significant? Yes. Clinically significant? Maybe? Adverse effects: nausea, vomiting, diarrhea, dizziness, tremor, and bradycardia 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. 2012 Mar 8; 366(10):893-903
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