An Estrogen Trial to Delay the onset of Alzheimer’s Disease in Memory-impaired Women

Dr. Mary Tierney
Senior Scientist and Director of
Geriatric Research
Sunnybrook and Women's College Health Sciences Centre

Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 64% of dementia cases in Canada. It is a progressive neurodegenerative disorder that currently afflicts more than 161,000 Canadians and is expected to affect approximately 800,000 by the year 2030.

A recent accumulation of laboratory, epidemiological and small clinical-trial studies suggest that estradiol, the principal gonadal hormone in females, may delay or prevent the onset of AD, and may also improve cognition in women with the disease. These observations raise the possibility that women taking postmenopausal hormone replacement thera-py (HRT) may be at significantly lower risk for AD. Thus, there is a compelling and urgent need for randomized, placebo-controlled clinical trials to determine whether estrogen replacement can prevent or delay the course of AD. This urgency is made greater by recent studies that have identified cognitive tests and genetic risk factors that enable earlier diagnosis of AD and enable the identification of those most at risk for the disease. For example, our previous research has shown that two neuropsychological tests and two demographic covariates (referred to below as the Alzheimer predictive index) predicted, over a two-year period, with 80% accuracy, the onset of AD in memory-impaired individuals without dementia.

Lithium--The Use of One of Psychiatry’s Oldest Drugs in Society’s Oldest Individuals

Sheldon Singh, BSc

Since the mid-19th century, it has been postulated that lithium, a small mono-valent cation, may be useful in the treatment of mania and depression. However, it was not until 1949, when Cade tested the effects of lithium on 10 patients with mania and depression, that its dramatic benefits were noted.¹ Today, lithium is the most extensively studied psychotropic medication. It has remained part of the treatment regimen for mood disorders and is the standard by which newer agents are frequently measured.²

This article will give an overview of the use of lithium in bipolar affective disorder with special consideration to the use of lithium in the elderly population.

Mechanism of Action of Lithium
Bipolar affective disorder or manic-depression is a very serious psychiatric disorder, characterized by abrupt switches from mania to depression. The etiology of this disturbance has not been identified. Research indicates that excess catecholamine activity may be present in the manic phase. It has been postulated that since anticholinergic agents cause mania, a decrease in the cholinergic system may also be involved in the manic phase. However, since the cholinergic system is also implicated in the depressive phase, the exact mechanism of catecholamine and cholinergic involvement in bipolar disorder remains to be elucidated.

Adapting Drug Dosage for Elderly with Anxiety

D'Arcy L. Little, MD, CCFP
Director of Education and Research
York Community Services, Toronto, ON

Epidemiology
Many studies and review articles have emphasized the fact that anxiety disorders, in general, are less prevalent among the elderly than among young adults.^1-5 However, some degree of controversy regarding the prevalence of anxiety among the elderly does exist in the literature. A recent review by A. Flint of the University of Toronto concludes that these disorders are rare in the elderly.¹ Fuentes and Cox of the University of Manitoba argue, on the other hand, that current research on anxiety in the elderly uses instruments and criteria that may not be valid vis-à-vis the elderly. It is their contention, therefore, that these instruments underestimate the validity of findings concerning anxiety in this age group.^1,2

Statistically, anxiety disorders are the second most common type of psychiatric disorder affecting older people next to cognitive impairment.² They are relatively common in late life, and are a cause of significant morbidity.⁸ While actual prevalence rates vary slightly from study to study, anxiety "feelings" reportedly occur in up to 20%² of the North American population of elderly people, and anxiety disorders in 3.5 to 5.5% in this population.

The Wonders of Acetaminophen: It Also Protects From Colon Cancer

91st annual meeting of the American Association for Cancer Research

While a number of analgesics are shown to inhibit tumour growth, anti-cancer properties of acetaminophen appear to work earlier during the neoplastic process. According to the recent research at the New York Medical College in Valhalla, acetaminophen can prevent the beginning of colon cancer by blocking the action of food mutagens. Treatment of rats with acetaminophen prior to the administration of 3,2'dimethyl-4-aminobiphenyl (a carcinogen, similar to the one formed during cooking) "produced a marked cytoprotective effect," Dr. Gary Williams, principal investigator of the study, said at the 91st annual meeting of the American Association for Cancer Research. While these results are very exciting, clinical trials with people at risk for colon cancer are necessary to determine whether administration of acetaminophen would reduce this risk in humans.

RALES Trial Overturns Convictions About Spironolactone’s Role in Treating Severe Heart Failure

Tawfic Nessim Abu-Zahra, BSc, MSc

Presently, the standard therapy for heart failure consists of treatment with an angiotensin-converting enzyme (ACE) inhibitor, furosemide (Lasix) or other loop diuretic, and the possible use of a b-blocker or a positive inotropic agent such as digoxin (Lanoxin).¹ The goals of this therapy are to decrease blood volume, increase cardiac contractility and inhibit the neuroendocrine effects of the renin-angiotensin-aldosterone system (RAAS). Since ACE inhibition suppresses aldosterone release, treatment with ACE inhibitors was considered sufficient for blocking the effects of aldosterone in patients with heart failure.^1,2 Thus, the addition of the aldosterone receptor antagonist spironolactone (Aldactone) was considered unnecessary and, given the threat of hyperkalemia, continued to be contraindicated.1 However, contrary to this conventional view, results of the Randomized Aldactone Evaluation Study (RALES) have shown that spironolactone treatment can reduce morbidity and mortality in patients with severe heart failure.

Clopidogrel versus Ticlopidine as Drug Therapies for Prevention of Cardiovascular Events

Shechar Dworski, MSc

Aspirin has been the traditional drug of choice for preventing cardiovascular events in cerebrovascular, cardiovascular, and peripheral vascular disease. However, many recent studies comparing aspirin to ticlopidine and clopidogrel in terms of efficacy and side effects, have produced results which favor these new antiplatelet drugs. Clopidogrel is the newer of the two drugs, and consequently, fewer studies have been done with it. Still, clopidogrel has shown promise as an alternative to ticlopidine; it is safer and has similar efficacy. However, studies are lacking to show that clopidogrel works equally well in all possible clinical situations, whereas ticlopidine's effectiveness has been proven in settings such as post-coronary stent insertion. Nevertheless, studies done with clopidogrel have shown it to be useful in many instances, such as secondary prevention after an initial cerebrovascular (TIA/ stroke) event. Most studies compare the two drugs against aspirin, but not directly against each other. Even so, it has become clear that clopidogrel produces fewer side effects, and is safer than ticlopidine. This article will present some of the information available about these two drugs to help the reader decide which antiplatelet agent to use.

Atypical Antipsychotics (including Risperidone and Olanzapine): Indications in Dementia

Philip Dopp, BSc

Dementia manifests itself in many ways within elderly populations. Given that symptoms associated with dementia, such as psychosis or behavioral disturbances, are common reasons for nursing home placement, it is not surprising that between 40% and 90% of residents of such institutions have some degree of dementia.^1,2 In recent years, atypical antipsychotics such as risperidone and olanzapine have been used with increasing frequency to deal with these distressing symptoms of dementia. Because of their favorable side effect profile, when compared to typical antipsychotics, and because studies have shown them to have equal, if not greater efficacy than typical antipsychotics, many geriatric psychiatrists recommend atypical antipsychotics as first-line treatment for psychosis and aggression in dementia.

The behavioral problems associated with dementia can be categorized as either non-aggressive or aggressive. Nonaggressive behavior includes wandering, pacing, bossiness, complaining and attention-seeking acts, while aggressive behavior includes hitting, pushing, scratching, biting, kicking and screaming. Management of these problems depends upon both the severity of the problem and the potential for the patient to harm themselves or others. In all cases, nonpharmacologic interventions, such as distracting the patient from the problem behavior, creating a structured environment for the patient and developing support groups for the caregiver, are appropriate.

Drug-Induced Depression--Diagnosis and Management

Kathleen Jaques Bennett, BSc, MSc

Drug-induced depression is a type of depression that is caused by a drug or combination of drugs. It can be difficult to diagnose and manage, especially in the elderly. A depression must first be diagnosed and a temporal relationship with a drug or drugs must be identified in order to make an accurate diagnosis of drug-induced depression. While there are a number of treatment options, the management of drug-induced depression is complicated if the drug is an indispensable medication. The management of this type of depression is further complicated if there is no substitute for the offending medication. Elderly people consume large numbers of prescription and non-prescription drugs. This group of people is often taking several drugs concurrently and has less tolerance for medications.¹ The elderly are particularly susceptible to drug interactions and adverse drug reactions (ADRs) which can lead to drug-induced depression.¹ This group also presents more difficulty in terms of managing the condition.