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Recent Additions to our Alzheimer’s Disease Arsenal

Recent Additions to our Alzheimer’s Disease Arsenal

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New Cognitive Enhancers Prevent Breakdown of Acetylcholine

Karl Farcnik, BSc, MD, FRCPC
Michelle Persyko, Psy.D, C.Psych

Psychiatrist,
Division of Geriatric Psychiatry,
University Toronto
Part-time staff,
Toronto Western Hospital

Introduction
Acetylcholinesterase (AchE) inhibitors have now become the medications of choice for first-line therapy in the treatment of Alzheimer's Disease (AD).1 In Canada, there are currently only two drugs that have been approved for the treatment of mild to moderate Alzheimer's Disease; these are donepezil (Aricept)2 and rivastigmine (Exelon).3 They have greater central specificity, and a much more favourable side effect profile, than do earlier AchE inhibitors such as tacrine (Cognex). Their role in the treatment of this disease is significant, since research is showing that they impact not only on the cognitive deficits associated with AD, but also help to preserve activities of daily living (ADL) and decrease behavioural problems. Cognition and ADL are both areas that are affected by Alzheimer's disease.4 Administration of these medications has been shown to be beneficial throughout the disease process. This paper describes donepezil and also rivastigmine, which is the newest AchE inhibitor that has been approved in Canada.

Manipulation of Dopaminergic Pathways is Mainstay of Pharmacological Treatment of PD

Manipulation of Dopaminergic Pathways is Mainstay of Pharmacological Treatment of PD

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The history of the use of pharmaceuticals to alleviate the symptoms of Parkinson's disease (PD) began 125 years ago, when belladonna alkaloids were first used in an attempt to control severe drooling in patients suffering from PD. These alkaloids possess anticholinergic activity, and unexpectedly, they alleviated other characteristic symptoms of PD, which include tremor, rigidity, akinesia and postural instability. However, it was not until 1958 that researchers discovered the presence of high levels of dopamine in the striatum of the brain and showed that the dopamine precursor (levodopa or L-dopa) reversed the tranquillization and parkinsonian-like motor impairments induced by treatment with reserpine. This set the stage for the development of the first real pharmacotherapy for treatment of PD.

Sanjiv CC, DM,
Tsui JKC, MD, FRCPC
Neurodegenerative Disorders Centre,
University of British Columbia,
Vancouver, BC, Canada

Dopaminergic Agents
At present, there is no pharmacological cure for Parkinson's disease (PD) and only the symptoms of the disease can be treated. There is no firm evidence to support the notion that any drug has a neuroprotective action in PD; therefore, the mainstay of current drug therapy is the manipulation of the dopaminergic pathways.

Levodopa (L-DOPA)
L-dopa is the most commonly prescribed medication for the treatment of PD.

How to Differentiate Between PD and Other Parkinsonian Syndromes

How to Differentiate Between PD and Other Parkinsonian Syndromes

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Janis Miyasaki, MD, FRCPC
Mount Sinai Hospital,
Movement Disorders

Each year Parkinson's disease (PD) affects 4.5-21 people out of every 100,000. The prevalence rate is 200/100,000 members of the population. As the population ages, the prevalence can be expected to increase since the risk of developing PD steadily increases with each decade of life.1 The cardinal symptoms of PD are tremor, rigidity, akinesia and postural instability.2 A patient is diagnosed with Parkinson's disease based on him/her having a history consistent with PD, and showing the clinical signs on examination. Therefore, the physician must be familiar with the classic appearance of each sign of PD and with the alternative diagnoses that are implied by any variance in symptoms.

Tremor
The tremor in PD is classically 3-5 Hz and is described as pill-rolling, due to the rhythmic opposition of the index finger and thumb. Tremor is seen at rest, however, in some cases it may only be seen if the patient is distracted by the use of manoeuvres such as mental arithmetic. While the patient is walking, the affected arm will often shake. Anxiety markedly increases the tremor, whereas it abates during sleep. Tremor may also be seen with postural maintenance or during a physical action. If the postural or kinetic component of the tremor is predominant, the physician should consider an enhanced physiologic tremor or essential tremor as the diagnosis.

Refinements to Surgical Treatment for Parkinson’s Disease

Refinements to Surgical Treatment for Parkinson’s Disease

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Basal Ganglia Motor Circuit is Target Site for Surgical Intervention

Farooq I. Khan, MD,
Robert Chen, MBBChir, MSc, FRCPC
Movement Disorders Centre,
Division of Neurology,
Toronto Western Hospital,
University of Toronto

Parkinson's Disease (PD) was first described by James Parkinson in 1817, and is a neurodegenerative disease that is characterized by tremor, bradykinesia, rigidity and postural instability. It results from the degeneration of the dopaminergic neurons in the substantia nigra (pars compacta) causing alterations in the basal ganglia circuitry; this circuitry is responsible for modulating and facilitating motor function through the cerebral cortex. The evolution of the treatment for PD has relied on both pharmacological and surgical approaches, arguably the most important of which was the discovery of levodopa in the early 1960s. Since then a number of other pharmacological agents such as monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, and dopamine agonists, have played a vital role in the amelioration of disability arising from this disease. Unfortunately, long term pharmacotherapy, especially with levodopa, has caused problems of its own, namely the occurrence of fluctuation and dyskinesia. For these and other reasons that will be discussed, surgery has offered a ray of hope to combat this eventually crippling disease.

Serendipity and the Origin of the Lens Implant in Cataract Treatment

Serendipity and the Origin of the Lens Implant in Cataract Treatment

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In 1942, a young British flight surgeon, Ridley, made an outstanding discovery that was to shape the future of cataract treatment. Cataracts result from the clouding of the lens of the eye, which leads to blurred vision. As with the lens of a camera, the lens of the eye functions by focussing light rays onto the retina at the back of the eye, which then transmits this visual information to the brain. For the light to pass through and reach the retina, the lens must remain clear. Cataracts result when the natural lens of the eye becomes cloudy; they are not the product of a growth or the accumulation of film over the eye.

While examining injured fighter pilots, Ridley noted that when plastic slivers from the shattered windshield of an airplane cockpit entered the eye, some pilots had a severe reaction, whereas other pilots had no reaction at all. At the time, the accepted belief was that any foreign material entering the eye would cause a severe reaction until it was removed. Ridley wanted to understand why some pilots showed no reaction to the presence of a piece of plastic in their eye. Further investigation led him to realize that it was only the pilots of Spitfires who did not suffer any complications, whereas pilots flying all other British fighter planes--including captured German pilots flying Messerschmitts--were all severely affected. The young surgeon then discovered that Spitfire plastic came from a different company, ICI, that produced a type of plastic material, polymethyl methacrylate, which could be tolerated by the human eye.

When the war ended in 1945, Ridley turned his attention to cataract surgery. Treatment at the time involved removing the diseased cataract lens and giving the patient thick, heavy glasses that limited their peripheral vision and magnified objects by 30 %. Ridley decided that a better technique for cataract treatment would be to replace the human lens with a lens made of the plastic that he had discovered during the war. On 19 November 1949, at St. Thomas's Hospital in London, he performed the first lens implant on a cataract patient.

Today the treatment of cataracts still relies solely on surgical techniques; there is no medication or diet that can stop a cataract once it has begun to form. A cataract may develop rapidly over a period of a few months or it may grow very slowly over several years. Typically, this process only occurs in a single eye, although eventually, often after months or years, a cataract may develop in the second eye. Most cataracts are related to aging, although they may also be congenital, the result of a medical problem such as diabetes or of a trauma to the eye.

A cataract rarely causes damage if it is left in the eye, except in cases in which there is blurred vision. There are very rare cases, however, of cataracts, when left in the eye long past the stage of blindness, causing inflammation and glaucoma. With the current methods of removal, surgery can be performed successfully at any stage of cataract development.

The only treatment for a cataract is the removal of the cloudy lens. There are various methods of surgically removing a cataract, and the specialist must decide which method is most suitable for each individual patient. For a description of the three main surgical procedures that are available for cataract extraction, and a list of the advantages and disadvantages of these techniques, please see the full article by Dr. Marvin Kwitko on our web site at www.geriatricsandaging.ca.

Dr. Marvin Kwitko performed his first lens implant operation at Bellechasse Hospital in Montreal in 1967. In 1968 he joined St. Mary's Hospital, and under the former chief, Dr. Gaston Duclos, continued this work there. Dr. Kwitko has trained more than 350 surgeons from Canada, the U.S. and abroad. He is currently the Chief of Opthalmology at St. Mary's Hospital in Montreal and an Associate Professor of Ophthalmology at McGill University.

Intramuscular Form of Atypical Antipsychotic Announced

Intramuscular Form of Atypical Antipsychotic Announced

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Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging

Due to a favourable side effect profile and high efficacy when compared with typical antipsychotics, atypical drugs are becoming increasingly recommended as first-line treatments for agitation and psychosis related to schizophrenia, manic depression, and behavioural disturbances associated with dementia. At the recent XXII International Congress of Neuro- psychopharmacology (CINP) in Brussels, a new study evaluating an intramuscular (IM) form of Olanzapine (Zyprexa) was presented. An IM form of antipsychotics can be crucial for the rapid control of a patient's psychotic symptoms in an emergency setting. This is the first time that an atypical antipsychotic is available in IM form. The study has just been completed and will be published shortly. Dr. Karena Meehan, M.D., clinical research physician for Eli Lilly and Company and the lead physician for the IM project with responsibility for the Canadian and American groups, agreed to answer a few questions about recent studies on Olanzapine and the use of this drug in the elderly.

Q: Your group has recently presented data comparing the effect of a new IM-formulation of the antipsychotic olanzapine with IM-haloperidol. What were the objectives and the results of your study?

A: The study was designed to compare olanzapine with an older typical antipsychotic.

Cancer, Cellular Senescence and Longevity--The Telomere Connection

Cancer, Cellular Senescence and Longevity--The Telomere Connection

Teaser: 

Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging

The relationship between aging and cancer has its basis in cell cycle alterations. While multiple factors affect cell cycle progression, recent research has directed a great deal of attention to telomere length as a key factor affecting mammalian cell proliferation. This article discusses recent findings with respect to the role of telomeres and telomerase in cancer, cellular aging, and longevity.

Telomeres are short DNA repeats located at the ends of eukaryotic chromosomes. Telomeres cap chromosomal ends preventing the loss of important genes during cell division. With every cell division, the length of telomeres decreases unless it is corrected by telomerase, a ribonucleoprotein enzyme that extends the telomeres by adding hexameric nucleotide repeats to the ends of chromosomes. In humans, telomeres are short, and telomerase activity is low in many somatic tissues but is present in germ cells, activated leukocytes, and stem cells from a variety of organs. The study of telomeres has been hampered by the fact that classical animal models, such as mice, have highly active telomerase. This results in long telomeres that do not shorten enough during the animal lifespan to play a significant role in cellular aging. Recently, a genetically altered telomerase-deficient mouse model has been created by a group of researchers at Harvard.

Overcoming Glaucoma: Laser versus Incisional Surgical Approaches

Overcoming Glaucoma: Laser versus Incisional Surgical Approaches

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Choice of Treatment is not Limited by Age but is Case-Specific

Robert M Schertzer, MD, FRCSC
Glaucoma & Anterior Segment Surgery
Multimedia Technology
Medical Director Visual Field and Optic Nerve Head Imaging Units
VHHSC/UBC Eye Care Centre

When pharmaceutical treatment of glaucoma proves ineffective, several surgical options remain available. In fact, some types of glaucoma may be best handled with immediate surgical intervention, even without prior medical management. Ocular surgery is any procedure that causes an alteration in the structure of the eye and can be laser (using a light) or incisional (using microsurgical blades). The type of surgical intervention indicated will depend on the mechanism of the glaucoma.

Laser surgery
There are three types of laser surgery used in treating glaucoma: trabeculoplasty, iridotomy, and cycloablation.

Trabeculoplasty, usually performed with an Argon green laser, is the application of laser energy next to the drainage channels (trabecular meshwork) around the circumference of the iris inside the eye (the coloured part of the eye.) This is used only for open-angle types of glaucoma, especially chronic ("primary") open angle glaucoma, pseudoexfoliation glaucoma, or pigmentary glaucoma.

Pharmaceutical Management of Glaucoma

Pharmaceutical Management of Glaucoma

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Reviewing the Major Classes of Antiglaucoma Medication

Catherine M. Birt, MA, MD, FRCSC
Sunnybrook & Women's College
Health Science Centre,
Assistant Professor,
University of Toronto

Medical management of glaucoma is a field that has expanded dramatically over the past five or six years. Since aging is one of the major risk factors for the development of glaucoma, it is an area that is of great relevance to anyone managing geriatric patients. The purpose of this article is to review the five major classes of antiglaucoma medications, the drugs that are currently available in each class, their indications and their side effects.

Glaucoma is considered to be an optic neuropathy with characteristic optic nerve damage (with loss of the neuroretinal rim and an increased cup-to-disc ratio) and visual field changes (with arcuate field defects progressing to complete loss of peripheral vision). Intraocular pressure (IOP) is not part of the definition of the disease, as many people with statistically elevated IOP do not develop the neuropathy, and many patients with statistically normal IOP do. Intraocular pressure is considered a major risk factor for the development of glaucoma. Other risk factors include advanced age, race, positive family history, myopia, and systemic factors such as diabetes and hypertension. Glaucoma is generally divided into open versus closed angle, and each of these can be subdivided into primary and secondary subtypes.

The Psychosocial Cost of Sensory Deprivation

The Psychosocial Cost of Sensory Deprivation

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Kathleen Jaques Bennett, BSc, BSc, MSc

In Ontario, 71% of the individuals with poor vision are over 65 years of age. To make matters worse, these seniors often suffer from additional sensory deprivation in the form of hearing loss.1 Sensory deprivation can be defined as the partial or complete loss of any of the five senses. It can lead to embarrassment, social isolation, depression, or the labelling of the patient as demented or infantile by family and caregivers. Vision and hearing loss are strongly correlated to an increased risk of mortality over a five-year period,2 probably because the psychosocial effects take an enormous toll on the afflicted individual. The partial or complete loss of the senses can lead to diminished quality of life, and may predispose an elderly person toward other conditions.

Types of Sensory Deprivation
Sensory deprivation can involve the loss of only one sense, or the combined loss of several senses. The loss of visual acuity associated with age often begins with the development of presbyopia. Presbycusis, the loss of hearing, is more prevalent among men than women.7 As well, touch, taste and smell become less acute with time. All of these forms of sensory deprivation undermine an elderly person's ability to live independently, increasing dependence on caregivers, and can result in the infantilization of the elderly individual. When sensory loss is coupled with another condition such as diabetes, the handicap becomes even more severe.