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

Cholinesterase inhibitors are a treatment option for most people with Alzheimer’s disease of mild to moderate severity. This article offers an approach to their use, based on the recommendations of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Treatment decisions must be individualized. Monitoring includes evaluating both safety and effectiveness, which entails more than just assessing cognition. Treatment is clinically beneficial when there is evidence of improvement, stabilization, or a slowing of the rate of decline seen prior to the start of treatment without unacceptable side effects.
Key words: dementia, Alzheimer’s disease, cholinesterase inhibitors, safety, effectiveness.

Kannayiram Alagiakrishnan, MD, MPH, FRCP(C), Associate Professor, Division of Geriatric Medicine, Department of Medicine, University of Alberta, Edmonton, AB.
Cheryl A. Sadowski, BSc(Pharm), PharmD, Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB.

Cholinergic deficits are seen in the brains of individuals with non-Alzheimer’s dementia. Antidementia drugs such as cholinesterase inhibitors and memantine have showed some cognitive and behavioural benefits in non-Alzheimer’s dementia trials, but more evidence is needed to define their role.
Key words: mixed dementia, cholinesterase inhibitors, Lewy body dementia, Parkinson disease dementia, vascular dementia.

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.

Chris MacKnight, MD, MSc, FRCPC, Associate Professor, Department of Medicine, Dalhousie University, Halifax, NS.

Three cholinesterase inhibitors are available in Canada for the treatment of mild and moderate Alzheimer’s disease. As the three agents differ in their pharmacology, switching among them does sometimes make sense. Switching may be necessary because of intolerance, lack of response, and occasionally loss of response. This article will describe how and when to switch cholinesterase inhibitor.
Key words: Alzheimer’s disease, treatment response, cholinesterase inhibitors, switching, dementia.

Sudeep S. Gill, MD, MSc, FRCPC, Assistant Professor, Division of Geriatric Medicine, Queen’s University, Kingston, ON.

Delirium is common among hospitalized older adults and is associated with significant morbidity and excess mortality. Despite its prevalence and consequences, delirium is often underrecognized and undertreated. Antipsychotic drugs are commonly used to manage symptoms of delirium, but few controlled trials exist to support their efficacy and safety in this setting. Several recent studies have focussed on preventing delirium in high-risk populations. Clinical trials have demonstrated benefits with multifaceted nonpharmacological interventions, but widespread implementation of these interventions has not yet occurred. Two recent drug trials evaluated an antipsychotic and a cholinesterase inhibitor to prevent delirium, but neither trial demonstrated a reduction in incident delirium. At present, the most promising approach involves targeted, multifactorial interventions that focus on preventing delirium in high-risk patient groups. More work is needed to facilitate the implementation of these evidence-based strategies.
Key words: delirium, prevention, treatment, antipsychotic drugs, cholinesterase inhibitors.

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.

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.htm

Ann Schmidt Luggen, PhD, GNP, Professor, Department of Nursing and Health Professions, Northern Kentucky University, Highland Heights, KY; Gerontological Nurse Practitioner, Evercare, Cincinnati, OH, USA.

Medical management of Alzheimer’s disease patients involves drugs that temporarily relieve or stabilize symptoms, or lessen the expected decline in cognition, function, and behaviour, but ultimately fail to halt progression of the disease. Commonly used agents in the management of early- to mid-stage dementias--albeit with modest outcomes--are the cholinesterase inhibitors (ChEIs). Antipsychotics have been used with mixed success to treat psychiatric symptoms that occur in 30-60% of patients with moderate-to-severe AD. In the terminal stages of dementia, palliation of symptoms and a focus on comfort care is important. Management of pain and relief from depression and anxiety are useful.

Key words: dementia, Alzheimer’s disease, cholinesterase inhibitors, behaviour, antipsychotics.

David F. Tang-Wai, MDCM, Department of Medicine (Neurology), University of
Toronto, University Health Network, Toronto, ON.

Keith A. Josephs, MST MD, Department of Neurology, Mayo Clinic, Rochester, MN, USA

Neurodegenerative diseases commonly affect cortical and subcortical structures, resulting in clinical features of mixed dementia and parkinsonism. Dementia, albeit an uncommon presenting feature of Parkinson’s disease, may become a complication with disease progression. In this review we discuss the relationship of dementia and parkinsonism. We outline a clinical approach to the diagnosis and management of dementia with Lewy bodies and emphasize the importance of understanding the complexity of the disease, for which in-depth knowledge of medication side-effect profiles is a must if treatment is to be undertaken. We also briefly discuss progressive supranuclear palsy, corticobasal syndrome, and vascular dementia with parkinsonism.

Key words: Parkinson’s disease, dementia with Lewy bodies, visual hallucinations, fluctuations, acetylcholinesterase inhibitors.

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.