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Alzheimer

Alzheimer’s Disease and Related Disorders Annual 2001

Alzheimer’s Disease and Related Disorders Annual 2001

Teaser: 

Editors: Gauthier S, Cummings JL

Reviewed by: Dr. Barry Goldlist, Editor in Chief, Geriatrics & Aging.

As is my usual practice when reviewing multi-authored textbooks, I immediately went to the list of contributors to see how representative they were of the broad community of experts. In this book, only two of the contributors are from countries other than the United States. One of these, Dr. Serge Gauthier, the eminent Canadian neuroscientist, also acts as an editor. Despite this relative imbalance, the book is excellent and of value to any physician with an interest in Alzheimer disease. Specialists and researchers will particularly enjoy the cutting-edge scientific chapters, including one on amyloid processing by Dr. Greg Cole, and Dr. Gauthier's thoughtful perspective on the past failures and future prospects of the use of muscarinic agonists in Alzheimer disease. Any physician, whether primary care provider or specialist, could benefit from the chapters on depression in dementia, the use of antipsychotic drugs in dementia and the management of late stage dementia. I was particularly impressed by the scientific rigour of the chapter on assessing competency for treatment consent capacity and financial capacity by Marson and Briggs.

With any such text, the lag between writing the chapter and publication means that the latest information cannot always be included. The same week that I reviewed this book, for example, I read an article in the Archives of Neurology on increased B-secretase activity in the Alzheimer disease brain that potentially contradicted some of the assumptions about disease pathogenesis in the book's first chapter. Although I enjoyed Professor Schelten's scholarly review of neuroimaging in the evaluation of dementia, I am not sure there is Level 1 evidence for his assertion that one MRI examination during the course of a dementia evaluation can hardly be judged to be optional any more.

Despite these minor quibbles, this is an excellent book that can be profitably read by any physician who cares for patients with dementia, particularly of the Alzheimer type.

Assessing the Response of Patients with Alzheimer Disease to Cholinesterase Inhibitors

Assessing the Response of Patients with Alzheimer Disease to Cholinesterase Inhibitors

Teaser: 

Serge Gauthier, MD, FRCPC, Neurologist, McGill Centre for Studies in Aging, McGill University, Montreal, QC.

Introduction
The advent of cholinesterase inhibitors (CI) as regular prescription drugs for the treatment of Alzheimer disease (AD) in mild to moderate stages has created opportunities for a proactive role among primary care practitioners with interest in a geriatric practice. The Canadian Consensus Conference on Dementia original report,1 and its update,2 clearly support the role of primary care physicians in the diagnosis and treatment of AD. A new challenge is the assessment of response to CI in individual patients. This review will examine the evolving expectations of response to treatment since 1986, when tacrine was first described as an effective drug,3 and will conclude with current realistic goals at therapeutic doses of donepezil, rivastigmine and galantamine--improvement in apathy peaking after three months of therapy and one year of stability for cognitive, functional and behavioural symptoms, followed by a decline parallel to natural history.4

Responders in Randomized Clinical Studies
The early descriptions of the response to CIs such as tacrine, included 'return to playing golf,'3 which set treatment expectations to a return to previous complex activities. A Canadian double-blind multicentre study did not find such dramatic effects.

Vitamin E and Alzheimer Disease

Vitamin E and Alzheimer Disease

Teaser: 

Jenny F.S. Basran, BSc, MD, and David B. Hogan MD, FACP, FRCPC
Division of Geriatric Medicine, University of Calgary, Calgary, AB.

Introduction
Recently, there has been growing interest in the use of vitamins for the treatment of various health conditions. One study has estimated that 35-54% of older Canadians take some form of vitamin or mineral supplement.1 Oxidative stress has been theorized to be an important contributor to select conditions, particularly those involving the cardiovascular and central nervous systems. Vitamin E is the only fat-soluble, chain-breaking antioxidant found in biological membranes4 and, therefore, has been investigated for its use in the treatment of ischemic cardiovascular disease in recent landmark studies such as the Heart Outcome Evaluation Study (HOPE)2 and Heart Protection Study (HPS).3

How Does Vitamin E Work?
Vitamin E is a generic term for chemical derivatives of tocopherol and tocotrienol.5 There are eight naturally occurring forms, but only a-tocopherol is found in human plasma, has the highest bioactivity and is the form used for medicinal purposes. a-tocopherol is found naturally in vegetable oils, almonds, sunflower seeds, walnuts, sweet potato, liver, wheat germ and egg yolk.6 Synthetic forms are available as vitamin capsules and in fortified foods.

The Presentation of Aphasia in Alzheimer Disease and Other Neurological Disorders

The Presentation of Aphasia in Alzheimer Disease and Other Neurological Disorders

Teaser: 

Karl Farcnik, BSc, MD, FRCPC, Psychiatrist, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.
Michelle Persyko, Psy.D, C.Psych, University of Toronto, Toronto, ON.
C. Bassel, M.A., University of Toronto, Toronto, ON.

Introduction
Aphasia has been described as a disorder of verbal communication due to an acquired lesion (or lesions) of the central nervous system involving speech production and/or comprehension.1 Aphasia does not involve deficits in global processes of communication, but only in its linguistic component, as evidenced by patients' ability to communicate through other means (e.g., complex nonverbal gestures).2 Aphasia is an integral part of the clinical presentation in Alzheimer Disease (AD). It is also an important diagnostic feature of other neurological disorders, which may be distinctive or overlap with AD. Clinicians should have a conceptual understanding of the different forms of aphasia as well as the conditions with which they are associated. The authors will review the diagnosis, assessment and treatment of aphasia, in the context of AD, Primary Progressive Aphasia (PPA), Frontotemporal dementia (FTD) and stroke.

The major types of aphasia can be classified as either fluent or nonfluent.

Genetic Counselling and Testing for Alzheimer Disease

Genetic Counselling and Testing for Alzheimer Disease

Teaser: 

Wendy S. Meschino, MD, CCFP, FRCPC, FCCMG
Clinical Geneticist,
North York General Hospital,
Toronto, ON.

 

"My mother has Alzheimer disease. Can I be tested to see if I carry the gene?" Such questions from patients are likely to be a familiar refrain to many physicians. While there is a great deal of discussion regarding the potential hereditary aspects of Alzheimer disease (AD), genetic testing is not appropriate for the vast majority of patients or their unaffected relatives. Genetic testing is possible only in selected situations where there is a significant family history of early-onset disease. In this article, we will explore how to take a family history of Alzheimer disease, how to recognize when genetic testing is appropriate, the critical issues to be discussed in genetic counselling and a brief review of the genes identified to date which are associated with familial Alzheimer disease (FAD).

In taking a family history, it is important to inquire about affected and unaffected relatives on both sides of the family. Details of the family history may be recorded in pictorial form as a pedigree (Figure 1). A minimum of three generations should be noted including siblings, parents, aunts, uncles, cousins and grandparents.

A New Treatment for Patients with Alzheimer Disease

A New Treatment for Patients with Alzheimer Disease

Teaser: 

G. Tong, MD, PhD
Jody Corey-Bloom, MD, PhD
Department of Neurosciences,
University of California San Diego, CA, USA.

 

Introduction
Alzheimer disease (AD), the most common form of dementia in the elderly, is characterized clinically by multiple cognitive deficits, including memory loss, visuospatial impairment, disorientation and language dysfunction. These features are often accompanied by behavioural and mood changes. A definitive diagnosis of AD can only be made by biopsy or autopsy. The major neuropathological features of AD are neuritic plaques and neurofibrillary tangles.

Cholinergic neurotransmission in the central nervous system (CNS) plays a key role in memory, attention, learning and other cognitive processes. Although other neurotransmitter deficiencies (e.g., noradrenaline, dopamine, serotonin and glutamate) have been noted, the cognitive impairments seen in AD patients have been largely attributed to decreased cholinergic neurotransmission. AD, in part, is characterized by the loss of neurons in basal forebrain cholinergic cells, especially in the nucleus basalis of Meynert, which projects to the cerebral cortex and hippocampus.

Alzheimer’s Disease--Treatable and With What

Alzheimer’s Disease--Treatable and With What

Teaser: 

A. Mark Clarfield

Several years ago at a public ceremony, a member of Europe's royalty forgot where she had put her reading glasses. Her husband may have thought that his regal spouse was showing signs of early Alzheimer's disease. However, Her Royal Highness clearly remembered that she wore glasses. In this distinction lies the difference between normal aging and dementia.

However, when the family doctor is concerned that a patient is suffering from one of the dementias--an insidious loss of higher cerebral functions including memory, judgment, affect, orientation, behaviour and language skills--further differentiation must be made. Most demented patients suffer from Alzheimer's disease or from brain damage resulting from multiple strokes. Unfortunately, in either of these situations there are few available treatments that can either reverse or limit the ongoing brain damage. For a fortunate few with a reversible cause for the dementia, early treatment can actually result in a significant improvement in the cognitive dysfunction.

Only a decade ago, the highest medical authorities held that anywhere from 20-40% of dementias were reversible. However, meta-analyses of the data indicated that reversibility occurred in no more than 11% of cases.1,2 Even more recent community-based studies indicate that, unfortunately, most dementias are incurable (although certainly not unmanageable); probably less than 1% fall into the reversible category.

Alzheimer’s Patients: When Should They be Told

Alzheimer’s Patients: When Should They be Told

Teaser: 


Clinical and Ethical Perspectives

Michael Gordon, MD, MSc, FRCPC
Vice President of Medical Services,
Baycrest Centre for Geriatric Care,
Professor of Medicine,
University of Toronto,
Toronto, ON.

David Goldstein, PhD
Director, Centre for Knowledge Transfer,
Baycrest Centre for Geriatric Care,
Professor of Psychology,
University of Toronto,
Toronto, ON.

The daughter told me (MG) that Dr. L. was prescribing Donepezil to her 87-year-old mother. "Do you agree with her decision?" she queried, then added, "We won't use the "A" word will we?" This recent exchange reflects the anxiety and fear that accompanies the communication of a diagnosis of Alzheimer's disease. It presents many complex clinical, legal and ethical problems, which may be challenging to many physicians.

Physicians are generally expected to communicate honestly and directly with their patients on matters of clinical significance. For patients suffering from Alzheimer's and other dementias, such straightforward communication may not always be appropriate. The patient may not be aware of his or her own cognitive changes and family members may balk at the idea of communicating such a devastating diagnosis. The physician may be left with a clinical and ethical conundrum: the desire to communicate honestly with the patient may conflict with the compelling desire to concur with the wishes of the patient's family.

Great Strides in the Year 2000, Great Hope for 2001

Great Strides in the Year 2000, Great Hope for 2001

Teaser: 

In the year two thousand we made great strides towards our goal of eradicating the suffering from Alzheimer's disease.

The brains of people with AD contain plaques of a peptide called b-amyloid, which many researchers believe causes dementia. b-amyloid is formed when a protein called amyloid precursor protein (APP) is broken down by the enzymes b- and g-secretase. In 1999, a group from Elan Pharmaceuticals demonstrated that vaccination with the b-amyloid peptide prevented plaque development in a mouse model of AD. However, at this stage it was not known if this reduction in the development of plaques would actually translate into improved cognitive function.

Three studies published in Nature at the end of last year suggest that this may, in fact, be the case. In the first paper, Chen et al., using a murine model of AD, provided evidence of age-dependent learning deficits that are associated with increasing levels of b-amyloid peptide. In the other two papers, the researchers examined, also in murine models of AD, the effects of immunization with the b-amyloid peptide on learning and memory, as well as on brain damage. Similar to the previous study, they both found a reduction in the formation of amyloid deposits in the brains of these mice. Perhaps more importantly, they show that immunization also allows the mice some protection from the learning deficits that normally accompany plaque formation.

Janus et al., show that when the mice are immunized with the b-amyloid peptide in the b-pleated sheet conformation that is eventually deposited, they produce antibodies that are specific to that particular conformation. What results is a reduction in the formation of plaques and the number of amyloid fibrils, without a significant reduction in the overall levels of b-amyloid peptide. This suggests that there may be a more toxic form of b-amyloid that can be specifically targeted without reducing, the potentially less harmful, soluble form of the protein. However, the second group used a more soluble form of the peptide and still found reductions in the proportion of the brain's neocortical and hippocampal regions that is covered by amyloid plaques. Both groups suggest that by only slightly reducing the deposition of b-amyloid we may protect the brain against the progression of AD.

The next step will be for pharmaceutical manufacturers to conduct preliminary trials on the safety of the vaccination, before larger scale testing can begin on its therapeutic effectiveness. The researchers believe clinical trials could begin on human subjects within the year.

References

  1. Chen G, et al. Nature 2000;408:975-79.
  2. Janus C, et al. Nature 2000;408:979-82.
  3. Morgan D, et al. Nature 2000;408:982-85.

The Importance of the Primary Care Practitioner in the Diagnosis and Management of AD

The Importance of the Primary Care Practitioner in the Diagnosis and Management of AD

Teaser: 

Serge Gauthier, MD, FRCPC
McGill Centre for Studies in Aging,
Montreal, Canada 

Alzheimer's disease (AD) is the most common cause of dementia, worldwide. It is well known that the incidence and prevalence of AD increase with age; therefore, because of the increasing longevity of our populations, and the large cohort of baby-boomers coming to maturity, more and more people will be affected by this condition. Fortunately, there are encouraging results from studies on symptomatic therapy and there is reason to hope that we may achieve long term stabilization and preventive treatment. This review will emphasize the important role of the primary care practitioner in the diagnosis and management of AD.

Clinical presentation of Alzheimer's disease
The Global Deterioration Scale describes the progression of AD as seven steps (Table 1), which is useful to describe the natural history of AD. This scale is familiar to most families who are caring for a patient with AD, and the primary care practitioner is often asked to describe the patient's current stage.