Michael J. Passmore, MD, FRCPC, Clinical Assistant Professor, Department of Psychiatry, Geriatric Psychiatry Program, University of British Columbia, Vancouver, BC.

The following review uses case studies to illustrate the importance of a biopsychosocial approach to the assessment and management of behavioural and psychological symptoms of dementia (BPSD). Practical BPSD assessment strategies are reviewed, in addition to evidence-based and guideline-supported recommendations for acute and long-term BPSD management.
Key words: dementia, behaviour, agitation, antipsychotic, memantine.

The accredited CME learning activity based on this article is offered under the auspices of the CE department of the University of Toronto. Participating physicians are entitled to one (1) MAINPRO-M1 credit by completing this program, found online at www.geriatricsandaging.ca/cme

David B. Hogan MD, FACP, FRCPC, Professor and Brenda Strafford Chair in Geriatric Medicine, University of Calgary, Calgary, AB.

A number of agents are available for treatment of Alzheimer’s disease (AD). They include drugs with a specific indication for AD, nutritional supplements, herbal preparations, and drugs approved for other conditions. Cholinesterase inhibitors (ChEIs) such as donepezil, galantamine, and rivastigmine are modestly effective for mild to moderate stages of AD. Memantine has a slight, beneficial effect on moderate to severe stages of AD. As ChEIs and memantine have different mechanisms of action, they can be used together. Antioxidants, B vitamins, anti-inflammatories, HMG-CoA reductase enzyme inhibitors, and sex steroids can not be recommended for the treatment of AD at the present time.
Key words: Alzheimer’s disease, drug therapy, cholinesterase inhibitors, memantine, dementia.

Ging-Yuek Robin Hsiung, MD, MHSc, FRCPC, Assistant Professor, Division of Neurology, Department of Medicine, UBC Clinic for Alzheimer Disease & Related Dementias, University of British Columbia, Vancouver, BC.

Dementia care represents a significant burden to our society. Although we are still far from any cure for dementia, there are several medications available for symptomatic management of Alzheimer’s disease and vascular dementia. These agents not only improve the cognitive and behavioural symptoms of dementia but may also help maintain patients’ functional independence and lessen caregiver stress. There are also a number of clinical trials currently in place to investigate new agents for treatment of Alzheimer’s disease. This article reviews the current medications available for Alzheimer’s disease and vascular dementia, as well as a number of promising agents that are under investigation.
Key words: Alzheimer’s disease, vascular dementia, cholinesterase inhibitors, donepezil, galantamine, rivastigmine, memantine.

Ging-Yuek Robin Hsiung, MD, MHSc, FRCPC and Howard Feldman, MD, FRCPC, Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC.

In the past decade, there have been numerous advances in our understanding of the molecular biology and pathogenesis of Alzheimer disease (AD). Although to date no pharmacological treatments have been shown to alter the pathology of AD, several medications have been proven to offer symptomatic improvement and to delay the progression of cognitive, behavioural and functional deficits. This article reviews the currently available medications for management of cognitive symptoms in AD, as well as other promising drugs that are under investigation.

Key words: Alzheimer disease, management, cholinesterase inhibitors, donepezil, memantine.

Introduction
An estimated 8% of the Canadian population over age 65 suffers from dementia, of which 60–70% is caused by Alzheimer disease (AD). The incidence of dementia doubles for every five years of increased age between 65 and 85 years.¹ The management of dementia is a significant burden to our health care system, with an estimated annual cost of $3.9 billion in 1991.² Epidemiologic studies suggest that if the symptoms of dementia can be delayed by just two years, prevalence will decrease by 25%, with significant savings to the long-term care of these individuals.

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.

Miriam Vale
Bachelor of Journalism

The latest, and, perhaps, most newsworthy advances in Alzheimer's research were presented at the popular hot topics session on July 13. The topics that were presented ranged from a discussion of age-related memory deficits in transgenic mice, to use of the drug memantine for the treatment of moderately severe to severe AD.

Dr. David Morgan of the University of South Florida's College of Medicine presented data showing that Ab vaccination blocked cognitive deficits in double transgenic mice carrying mutant amyloid precursor protein (APP) and mutant presenilin 1 (PS1).

The development of transgenic mice models with age-related deficits in learning and memory are quite useful for testing whether therapeutic approaches to AD could potentially reduce or prevent dementia. Using these double transgenic mice, the group found that they could detect the presence of a working memory deficit in mice doing the six-arm radial water maze task. According to Morgan, this test is similar to the registration and recall components of the clinical examination for dementia.

The underwater maze resembles a wheel with six spokes. In this test, the mice must find a hidden underwater platform in one of six channels joined at a central area. The mice must learn the location of the platform over four consecutive learning trials; they are then tested for retention 30 minutes after the last learning trial. The cycle is repeated everyday with only the location of the platform altered so that the mice cannot use reference memory to find it.

The researchers found that 12-month-old and 15-month old mice that had received a course of vaccinations from 4-months of age onwards performed as well as wild-type mice (control mice), in that they learned to navigate the maze with few errors. By contrast, age-matched, non-immunized, transgenic mice were unable to learn the task. The researchers also found that15-month old mice that received a shorter course of the vaccination reached almost the same performance level as the controls. However, the 'short-term' vaccination mice had almost no reduction in their Ab burden when compared to nonimmunized mice, suggesting that the plaques were not responsible per se for the observed cognitive deficits. The radial arm water maze is a sensitive measure of changes in working memory performance because it separates working memory from reference memory. Morgan expects that it may be effective in longitudinal studies

Dr. Barry Reisberg of New York University's School of Medicine, presented his findings from a placebo-controlled six-month trial of the drug memantine for the treatment of patients with moderately severe to severe AD. Memantine is a fast, voltage-dependent NMDA-receptor antagonist. It blocks the NMDA receptor in the presence of the sustained release of low glutamate concentrations and thereby attenuates the function of the NMDA receptor. The presentation only included phase III of the trial, which evaluated the efficacy and tolerability of memantine. The drug, which is already in use in Germany, may also be useful for the treatment of advanced dementia. Pre-clinical data suggest that the drug has symptomatic and neuroprotective properties. The 28-week double-blind trial tested the efficacy of the drug in 32 American centres. The eligibility of patients for the trial was based on their having been diagnosed with AD with a severity rating of five or six on the Global Deterioration Scale. Patients received either 10mg memantine or placebo. Though both treatment groups worsened over the trial period, overall the decline was smaller for the memantine treatment group. It produced statistically significant improvements in clinical global changes, function and cognition. Memantine also appeared to be safe and well tolerated by the study participants. According to Reisberg, "Neuroprotective properties of memantine, in addition to the symptomatic treatment effects reported, may have contributed to these results."