Emerging drug therapies for dementia are increasingly chosen to tackle molecular targets important in Alzheimer’s disease (AD) pathobiology. Amyloid oligomers, amyloid deposits, and neurofibrillary tangles (NFTs) are characteristic findings in AD. Hence, drugs that interfere with these proteinaceous aggregates are receiving the most attention: a) alpha, beta, and gamma secretase modulators, b) inhibitors of amyloid beta (Ab) aggregation, and c) anti-Ab immunologic strategies. Oxidative stress and inflammatory reactions appear part of a loop of neurotoxicity with the proteinacous aggregates. Antioxidants and anti-inflammatory compounds have thus received much attention. Finally, other compounds may work by a variety of other mechanisms.
Key words: Alzheimer’s disease, amyloid, secretase inhibitors, antioxidants, anti-inflammatory agents.

K. Farcnik, MD, FRCP(C), Psychiatrist, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.
M. Persyko, PsyD, CPsych, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.

Significant work has been done in the treatment of Alzheimer disease (AD) since cholinesterase inhibitors (CI) were approved in Canada five years ago. This has led to a better understanding of these drugs in terms of their different properties, therapeutic efficacy and indications for switching, and their use has since been extended to the treatment of AD with vascular pathology. Other treatments for AD, such as estrogens and non-steroidal anti-inflammatory drugs (NSAIDs), have also been evaluated further, while newer treatments, including a vaccine for AD, are currently in development. Although research outcomes have not always been positive, a significant effort is being made to achieve greater impact in a disease that is becoming ever more prevalent.

Cholinesterase Inhibitors
Currently, the CIs are the only class of drugs that have been proven efficacious in the symptomatic treatment of AD.¹ There are two types of CIs: acetyl and butyryl. Butyrylcholinesterase levels in the brain increase with the progression of AD, whereas levels of the enzyme acetylcholinesterase decrease.² The CIs approved in Canada that have demonstrated efficacy as well as a favourable safety profile are donepezil, rivastigmine and galantamine.