Joe_2019_BMJ_367_l6217

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid beta in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.