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IN THIS ISSUE PHARMACOTHERAPY OF ALZHEIMER'S DISEASE Acetylcholinesterase inhibitors continue to be tested for moderately severe AD Patients with moderately severe neocartical deficits should be targeted for cholinergic treatment Estrogen and donepezil is more effective in women with AD than donepezil alone It's too soon to conclude whether NSAIDS are beneficial in AD TREATMENT OF BEHAVIOURAL SYMPTOMS OF DEMENTIA Risperidone is associated with reducing aggression in elderly patients with dementia FUNCTIONAL CHANGES IN DEMENTIA Assessment of IADLs can help to identify older subjects with early dementia Functional measures may help clinicians select suitable interventions for patients with AD EPIDEMIOLOGY OF DEMENTIA IN CANADA-CSHA 2 Elderly dementia patients have higher mortality rates than those without it Cognitive decline increases in the elderly whotake calcium-channel blockers

EDITORIAL COMMENT

PHARMACOTHERAPY OF ALZHEIMER'S DISEASE Cholinesterase inhibitors (CI) have efficacy in treating symptoms associated with AD in mild to moderate stages (Gauthier, 1999). This efficacy may well extend into the moderate to severe stages since neocortical cholinergic deficits were not found to be significant until the severe stages of pathologically confirmed AD (Davis et al, 1999). Results of the international (primarily Canadian) study of donepezil in moderate to severe stages of AD will soon be available. The therapeutic effects of CI may be enhanced by estrogens in post-menopausal women, as was demonstrated with donepezil in a retrospective analysis (McRae et al). A prospective study is under way to confirm this important finding. On the other hand, NSAIDS should not be used for the management of AD symptoms, despite strong epidemiologic evidence to suggest a protective role, considering the lack of efficacy of the diclofenac-misoprostol combination (Scharf et al, 1999). Data will soon be available on the safety and efficacy of COX-2 selective inhibitors for the symptomatic treatment of AD. The excellent review by Wolfe et al (N Eng J Med, 340, 1888-1899, 1999) on NSAIDS and GI toxicity will be useful to interested readers.

Acetylcholinesterase inhibitors in the
treatment of Alzheimer's disease

Cholinergic markers in elderly patients
with early signs of Alzheimer disease

The effect of donepezil in combination
with estrogen in women with AD

THOMAS.MCRAE, JOHN ORAZE, NORMAN RELKIN, NEW YORK, NY

In this large, open-label study of community-based patients with mild to moderate Alzheimer's disease (AD) (n=1034), the cognitive performance of post-menopausal women was compared in those taking donepezil alone (n=449) or with estrogen (n=105) or with estrogen plus progesterone (n=49). Donepezil treatment was initiated at 5 mg/day and was increased to 10 mg/day at Week 4. Patients were evaluated using the standardized Mini-Mental State Examination (SMMSE), and were compared controlling for age and baseline SMMSE. In the Week 12 last observation carried forward analysis, mean improvement from baseline SMMSE was 1.06 for donepezil alone, 1.66 for donepezil, estrogen and progesterone (p=0.24) and 1.80 for donepezil and estrogen (p=0.04), with a similar pattern of results at Weeks 4, 8 and 12. This study supports the possibility that use of estrogen and a cholinesterase (ChE) inhibitor, in this case donepezil, results in better cognitive enhancement in women with AD than does a ChE inhibitor alone.

A double-blind, placebo-controlled trial
of diclofenac/misoprostol in Alzheimer's disease

TREATMENT OF BEHAVIOURAL
SYMPTOMS OF DEMENTIA

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EDITORIAL COMMENT

The tolerability and efficacy of low-dose risperidone relative to haloperidol and to placebo has been established in patients with dementia (De Deyn et al, 1999). The accompanying editorial by J. Cummings and D. Knopman (Neurology 53, 899-901, 1999) highlights the therapeutic value of the atypical neuroleptics (risperidone, olanzapine, quetiapine) and anticonvulsants (carbamazapine, valproate) in the management of behavioural symptoms of dementia. These medications are not a substitute but a complement to adequate staffing and proper environmental management of these symptoms.

A randomized trial of risperidone, placebo,
and haloperidol for behavioral symptoms of dementia

FUNCTIONAL CHANGES IN DEMENTIA

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EDITORIAL COMMENT

Since interference with functional abilities is a requirement for the diagnosis of dementia, there is a major interest in finding which instrumental activities of daily living (IADL) are most affected in early dementia. This issue is important in randomized clinical trials (RCT) that aim at delaying conversion from mild cognitive impairment to dementia with treatments such as alpha-tocopherol, donepezil, or COX-2 selective inhibitors. In a large scale epidemiology study from France, the following IADL were most sensitive for detection of early dementia: changes in ability to use the telephone, transportation, medication and finances (Barberger-Gateau et al,1999). These items are included in the Disability Assessment for Dementia (DAD) scale, developed in Canada and widely used in RCT (Gelinas et al, 1999).

Functional impairment in instrumental activities of daily living:
an early clinical sign of dementia?

Development of a functional measure for
persons with Alzheimer's disease:
the disability assessment for dementia

EPIDEMIOLOGY OF DEMENTIA
IN CANADA -- CSHA 2

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Mortality in elderly Canadians with and without dementia:
a five-year follow-up

Calcium-channel blockers and cognitive function in elderly people:
results from the Canadian Study of Health and Aging