Philip Dopp, BSc

The disturbing statistics with regard to the prevalence of osteoporosis among older women are well known. By 65 years of age, one in four women have experienced an osteoporotic fracture, and the rate of incidence rises to one in two by the age of 75. The incidence of hip fractures among women in the United States is 2 per 1000 patient years by the age of 65 and 30 per 1000 patient years by the age of 85.1 More importantly, hip fractures in the elderly are associated with a high mortality rate. Both men and women are between two and five times more likely to die during the first 12 months following a hip fracture when compared to age and sex matched controls without hip fractures. Given this and other serious consequences, there is much interest in discovering factors that can prevent or slow the rate of development of this disease.¹

Pathophysiology of Osteoporosis
Osteoporosis is the generalized, progressive diminution in bone tissue mass per unit volume which causes skeletal weakness, even though the remaining bone is normal morphologically. It is well known that factors that decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures include family history, white race, female gender, estrogen deficiency, low dietary levels of calcium and vitamin D, limited physical activity or immobility and medications such as corticosteroids.^1,2 Currently, there has been an increased interest in determining the role that genetic factors play in the pathogenesis of osteoporosis.

Internet Databases Offer Easy Access to Relevant Genetic Information

Kathleen Jaques Bennett, BSc, BSc, MSc

Familial hypertrophic cardiomyopathy (FHCM) is an inherited disorder that results in the thickening and stiffening of the myocardium, primarily in the left ventricle.¹ This disorder runs in families and may appear late in life. FHCM is produced by mutations in at least eight autosomal genes that are responsible for the synthesis of the sarcomeric filament proteins. These genes vary in terms of where the mutations are located.² FHCM is present in less than 0.5% of the population and has been associated with sudden death.³ The disorder varies both in its severity and in its clinical features, with more variants still being identified. There is some phenotypic heterogeneity with FHCM but the disorder is highly correlated in its physical expression to the mutation and its location, especially within families. Internet-based databases now exist to describe the characteristics of FHCM, specific mutations and loci, the epidemiology and the type of hypertrophy and the prognosis.⁴ FHCM has been a disorder associated with young people but was recently identified as having a late-onset variant that develops after age 50. This late-onset FHCM results from mutations in the gene for cardiac myosin-binding protein C (MBP-C) and cardiac troponin T (TNN-T).

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.

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.

Genetic Identification Promises Individually-tailored Treatments

Julia Krestow, BSc MSc

Mental illness is a term describing a group of disorders, all of which profoundly affect an individual's ability to think, feel, and act, and which result in a substantially diminished capa-city to cope with the ordinary demands of life. Mental illness can strike irrespective of age, gender, or race.¹ Although mental disorders were recognized as illnesses in the mid-18th century, suspicion and fear often overshadowed understanding. Gradually, advances in the fields of psychiatry, behavioural science, neuroscience, biology, and genetics have replaced trepidation with knowledge. Some common mental illnesses are schizophrenia, bipolar affective disorder and depression.

Researchers and clinicians have worked for decades to reduce the suffering of those with disabling disorders, and current treatments can alleviate symptoms for many. Unfortunately, there is no curative treatment, and the treatments which do exist can have side effects. Research has long shown that the risk of developing mental illness increases if another family member is similarly affected; this suggests a strong hereditary component. Exciting developments in molecular genetics and the neurosciences explain the cautious optimism in terms of insight gained into the causes of mental disorders.

Two Theories Linking DNA Damage and Aging: Free Radical/Oxidation vs. Telomere Shortening

Ruwaida Dhala-Vakil, BSc, MSc

There are many factors involved in human aging, and significant progress has been made in this field over the last few decades. Recent evidence from cloned calves suggests that scientists may not merely be able to reverse the cellular damage accumulating with age--they may, in fact, be able to prolong cell life. The cells from these cloned animals lived longer in culture and had longer telomeres than their normal counterparts. If this extension of the cellular life span can be translated into longer life for the entire organism, the calves may live fifty percent longer than normal.¹ Additionally, studies on antioxidants show that transgenic Drosophila (the fruit fly), which overexpress antioxidant genes, live 34% longer than controls.² This article will focus on both the free radical/oxidation theory of aging, and the role of telome-rase in aging.

Free Radical/Oxidation Theory of Aging
In 1956, Denham Harman suggested that there is an age-related accumulation of reactive oxygen species (ROS) which causes damage to cellular components. The damage is targeted to the proteins and DNA in the nucleus and mitochondria, as well as to the proteins and lipids in the cell membrane, and the proteins of the cytoplasm. Mitochondrial DNA is located near the inner mitochondrial membrane, close to the sites where free radicals form.

Recognizing the Clinical Features of Delirium can Save the Lives of the Hospitalized Elderly

Nariman Malik, BSc

Confusion in the elderly is a common problem. Its onset may be acute or chronic and progressive in nature. Confusion may be a symptom of delirium or dementia but it may also be associated with psychoses and affective disorders, in particular major depression.¹ This article focuses on delirium, one of the most common and frequently unrecognized causes of confusion in the elderly.

Delirium is a syndrome of disturbed consciousness, attention and cognition or perception, which develops acutely, fluctuates during the course of the day, and is a direct physiologic consequence of a general medical condition.^2-4 Delirious patients may also have psychomotor and emotional disturbances. In most cases, delirium is reversible upon treatment of the underlying medical condition.¹ Currently, a great deal of attention is being focused on this condition because of the huge impact it has on patients and their families, as well as on patient care costs. Delirium is a phenomenon that is common in hospitalized patients, and is associated with high morbidity and mortality rates, and significantly extended lengths of hospital stay.⁵

The incidence of delirium increases progressively after the fourth decade of life.

A. Mark Clarfield, MD

I had almost been convinced by Mrs. C. that her friend Sarah, after 50 years of friendship, had actually turned on her. On the surface, the story presented by my patient, who appeared well-groomed and intelligent, was certainly quite believable. I had read far more incredible tales in the Toronto Globe and Mail.

Apparently, the friendship between the two ladies went back many years. They had been born in the same little poverty-stricken Jewish shtetl (farming village) in Poland just after the turn of the century. They had both moved to Montreal where they married and brought up their respective families. The two ladies and their families shared summer holidays "at the lake," as well as their children's birthdays, baseball games and graduation celebrations and weddings.

Later in life, after both were widowed, the two women moved into separate but adjacent apartments in a subsidized seniors' home. They exchanged keys so that each could look after the other's apartment when the need arose.

It was just last year, my patient informed me, "that of all people"; Sarah had started stealing from her. First it was just little things, such as a quart of milk. But lately, as the stakes got higher and jewelry began to go missing, my patient became concerned. She confronted her friend Sarah who "blew her stack.

Christopher B. Overgaard, MSc, MD

Atrial Fibrillation and Elderly Patients
Atrial fibrillation (AF) is by far the most common cardiac arrhythmia, and is most prevalent among the elderly. One large study found that 70% of all patients with AF were between 65 and 85 years of age.¹ Many underlying conditions have been associated with the development of AF, including diabetes, hypertension, pulmonary disease, thyrotoxicosis, cardiomyopathy, and nonspecific conduction defects; the AF patient population is, therefore, a heterogeneous one.² Regardless of underlying cardiac pathology, this arrhythmia is associated with a doubling of mortality and is a very significant health issue for elderly patients.

AF occurs through the propagation of random waves of intra-atrial reentry, with many macroreentrant circuits moving throughout the atrial muscle.³ This chaotic pattern results in a random irregular rhythm, a significant decrease in stroke volume and cardiac output, and the risk of thrombus formation due to atrial stasis. Systemic embolization from an atrial clot is considered to be the most devastating, albeit potentially preventable, consequence of this disease process.²

Atrial Fibrillation, Stroke, and Bleeding Risk
Elderly patients with atrial fibrillation are at a fourfold higher risk of suffering a stroke than the age-matched general population.

Tracey Tremayne-Lloyd, BA, LL.B,
Tremayne-Lloyd Partners
Toronto, Ontario

More than just the catch-phrase of the day, 'Living Wills' appeared to be the answer for increasing patient control in end-of-life decisions, and a much sought-after solution for an aging population (but one that is increasingly sophisticated about treatment options). The issue of Living Wills was explored in the May/June 1998 edition of Geriatrics and Aging in an article entitled 'Living Wills Ease Patient's Fear' by Lawrence J. Papoff (please see our web site www.geriatricsandaging.com for this article). Recent research has demonstrated that the Living Will is an instrument well-liked by physicians and patients for its capacity to empower patients with independence when facing a life-threatening condition, but it is still surprisingly under-used. It is important for physicians treating geriatric patients to be aware of the extent to which Living Wills can be incorporated into their practice, and to consider their role in educating patients about the issue.