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.

Serge Gauthier, MD, FRCPC, McGill Centre for Studies in Aging, Montréal, QC.

Functional disability is an important component of Alzheimer’s disease. A number of scales are available to measure activities of daily living (ADL) throughout the course of disease, including instrumental as well as self-care activities. A randomized clinical study comparing donepezil to a placebo in moderate-to-severe stages of AD showed a stabilization of ADL decline over six months for patients on donepezil. Less time for ADL care was required by caregivers of patients on donepezil compared to those on placebos.

Key words: Alzheimer, therapy, activities of daily living, donepezil, caregiving time

Introduction
The importance of decline in activities of daily living (ADL) in older adults with dementia has been recognized in the condition’s diagnostic criteria, described as “significant impairment in social or occupational functioning” in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

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.

Eleanor Brownridge

Until recently, many general practitioners have been hesitant to diagnose Alzheimer's Disease (AD), especially at the mild and moderate stages. They believe that patients and their families don't want to hear this bad news and therefore don't push the issue.

"We have to work hard to change the attitudes of physicians," says Dr. Ron Keren, geriatric psychiatrist with the University Health Network, Toronto General Hospital. "We have to move away from stigmatizing Alzheimer's and start approaching it as any other serious disease. We need to talk frankly, openly and honestly with our patients." Research from the United States has shown that 80 percent of seniors want to know if they have dementia. Dr. Keren, who also practices at the Toronto Rehabilitation Institute and the Whitby Health Centre, says that in over seven years he has never had a patient who didn't want to know the state of his disease. "If you can't talk about it, how can you treat it?"

With the recent decisions of Ontario and Manitoba to reimburse donepezil (Aricept) in those provinces, physicians now have a treatment for mild to moderate dementia of the Alzheimer's type that can bring hope to all patients and their families, not just those who can afford it.

Donepezil inhibits the activity of acetylcholinesterase, thereby increasing levels of acetylcholine in the brain.

Donepezil (Aricept), is now being reimbursed to eligible Ontario patients by the Ontario Drug Benefit Program. Donepezil received Health Protection Branch (HPB) approval in August 1997. Until now, however, donepezil has not been reimbursed by any provincial health plan, including Ontario's public drug program which covers senior citizens and those on social assistance. People wanting donepezil have had to pay for it themselves or have it reimbursed by private insurance.

Effective June 1, 1999, eligible ODBP beneficiaries will have the cost of donepezil reimbursed. There are two categories of coverage. Those who have already been on donepezil treatment for more than 60 days, have a confirmed diagnosis of mild to moderate AD and meet the ODBP program criteria will be eligible for reimbursement of donepezil by the ODBP.

Others with a confirmed diagnosis and who meet the ODBP and program criteria but who have never taken donepezil (or have taken it for less than 60 days) will be enrolled in a 12-week trial prescription program, with the medication provided free of charge by Pfizer. The trial prescription program is administered by an independent pharmacy and healthcare company, Caremark Ltd., based in Mississauga, Ontario.

The patient and caregiver also will receive a Pfizer-sponsored program of educational material about AD, including a video, called TriAD and a patient diary. The physician will continue to be supplied with diagnostic and other support tools to help him or her evaluate and track the patient's progress.

At the end of the 12-week trial prescription program, those patients who have benefited from the treatment will be eligible for continuing treatment reimbursed by the Ontario government. All patients receiving reimbursement will be reviewed annually to ensure they are still benefiting from the treatment and thus remain eligible for reimbursement.

The major instrument used to measure eligibility and effectiveness will be the Mini Mental Status Exam (MMSE). A score of 30 represents full cognitive ability; persons with impairment caused by AD score lower and their scores diminish over time as the disease takes its toll on cognitive function.

To be eligible for coverage, persons with mild to moderate AD will have to have and maintain an MMSE score between 10 and 26. A score that drops below 10 is indicative of advanced cognitive impairment of the later stages of AD, for which treatment with donepezil would not be appropriate.

Patients, caregivers or healthcare professionals seeking more information about reimbursement for donepezil can call toll-free to 1-800-510-6141.

Extracts from the leaves of the Ginko biloba tree and Vitamin E are just two of the therapies being investigated for the treatment of Alzheimer's Disease

Neil Fam, BSc, MSc

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized clinically by a gradual onset of progressive memory loss with deterioration in patients' social and occupational function. Changes in mood, behaviour and perception are also problematic aspects of the disease. Neuropathologically, AD is associated with the formation of amyloid plaques and neurofibrillary tangles, with impaired synaptic function and neuronal cell death. In particular, patients with AD suffer the loss of cholinergic, noradrenergic and dopaminergic neurons. Loss of acetylcholine neurotransmission in brain areas involved in learning and memory is thought to underlie many of the cognitive symptoms of AD. This concept forms the basis of current therapeutic strategies which aim to increase available acetylcholine levels in the brain by inhibition of acetylcholinesterase.

Olya Lechky

A new multi-national clinical trial of donepezil (Aricept) confirms and augments the encouraging findings from previous multi-centre studies that the drug significantly improves cognition and global functioning in patients with mild to moderate Alzheimer's Disease (AD).

Presented by Dr. Serge Gauthier and colleagues at the McGill Centre for Studies in Aging in Montreal, the new trial provided the international (including Canadian) data showing efficacy and safety. Following HPB approval of donepezil last August, Canadian physicians for the first time have a highly specific, effective, non-toxic and well-tolerated drug with which to treat the rapidly growing number of older people affected by this progressive and ultimately fatal disease.

According to Dr. Gauthier, the large multi-centre trial published in Neurology (January 1998) showed that donepezil improved memory, orientation and the use of language in addition to the performance of daily functions such as bathing, dressing and eating. The new trial, reported at the 5th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy in April in Geneva, Switzerland, confirmed these findings.