Richard A. Wells, MD, DPhil, FRCP(C), Assistant Professor of Medicine, University of Toronto; Staff Physician, Leukaemia Group, Princess Margaret Hospital; Scientist, Ontario Cancer Institute, Toronto, ON.

In myelodysplastic syndrome (MDS), genetic mutations in bone marrow stem cells result in production of defective blood cells. These defective cells fail to meet the intrinsic "quality control" standards of the bone marrow and are not released into the circulation, leading to anemia, leukopenia or thrombocytopenia. In some, but not all, patients with MDS, there also is a greatly increased risk of development of acute myelogenous leukemia. Until very recently, therapeutic options in MDS were extremely limited. This article reviews recent advances in risk-based classification of MDS, and describes new therapies that promise to revolutionize our approach to patients with this disorder.
Key words: myelodysplastic syndrome, bone marrow, anemia, acute myelogenous leukemia.

Sudeep S. Gill, MD, FRCP(C), Research Fellow, Division of Geriatric Medicine, University of Toronto and Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, ON.
Shabbir M.H. Alibhai, MD, MSc, FRCP(C), Staff Physician, Department of Medicine, University Health Network, Toronto, ON.

Folate deficiency is relatively common in older adults. There is now growing interest in the roles played by folate and B vitamins in the metabolism of homocysteine. Recent studies have suggested a link between elevated levels of homocysteine and the risk of Alzheimer disease. In this article, we will focus on the physiology and pathophysiology related to folate and homocysteine metabolism. We have also included a discussion of the laboratory evaluation of these compounds. Finally, we review the evidence supporting the relationships between folate deficiency, hyperhomocysteinemia and the development of dementia.
Key words: folic acid, vitamin B12, deficiency diseases, homocysteine, dementia.

12 Deficiency in the Elderly

Sudeep S. Gill, MD, FRCP(C), Research Fellow, Division of Geriatric Medicine, University of Toronto and Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, ON.
Shabbir M.H. Alibhai, MD, MSc, FRCP(C), Staff Physician, Department of Medicine, University Health Network, Toronto, ON.

Vitamin B12 deficiency is a common disorder in older adults, but its diagnostic work-up and management can be complex. In this article, we review the metabolic pathways involving vitamin B12 and the various pathologies that can interfere with these pathways. This discussion provides a framework to understand the following section, which outlines an approach to the clinical examination, laboratory evaluation and treatment of subjects with suspected vitamin B12 deficiency.
Key words: vitamin B12, folic acid, deficiency diseases, dementia, aging.

Vikas Gupta MD, MRCP(UK), MRCPath, Department of Medical Oncology and Hematology, Princess Margaret Hospital/University Health Network; University of Toronto, Toronto, ON.

Old age is usually considered a significant risk factor for venous thromboembolism (VTE), and the incidence of VTE increases exponentially with age. Associated comorbid conditions such as heart failure, postoperative states, malignancy and long-term immobility contribute considerably towards the higher incidence of these hypercoagulable disorders in this subgroup of patients. The optimal, cost-effective laboratory work-up for underlying thrombophilic or hypercoagulable states is not clear in older patients. The main aim of this article is to review the inherited thrombophilic disorders and discuss their clinical relevance in older patients.
Key words: hypercoagulable disorders, thrombophilia, venous thromboembolism, risk factors.

With the popularity of herbs, botanicals and other natural remedies continuing to explode, a unique web-based resource recently launched by Memorial Sloan-Kettering Cancer Center will help fill the information gap for both medical practitioners and the general public.

The web resource includes monographs on 135 agents, providing clinical summaries of each, as well as the purported uses, mechanisms of action, adverse reactions, drug interactions and links to scientific research and critiques. The website provides invaluable information for physicians that is comprehensive and current, and will be continually updated by the Chief of Integrative Medicine at MSKCC and a pharmacist and botanicals expert. Discover what you don't know at: http://www.mskcc.org/aboutherbs.

A novel brain mapping technique has provided the first quantitative, dynamic visualization of the spreading wave of cortical atrophy in the brains of living patients with Alzheimer disease (J Neurosci 2003;23:994-1005).

Using this unique mapping method, Australian neuroscientists were able to visualize dynamic patterns of atrophy in 52 high-resolution MRI scans of 12 patients with AD and 14 elderly matched controls. Based on these scans, dramatic time-lapse videos were created, showing sequential loss of gray matter in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, while sparing sensori-motor areas. The visualized patterns of cortical atrophy correlated with the AD patients' progressively declining cognitive ability and mirrored the sequence of neurofibrillary tangle accumulation observed at autopsy. AD patients were found to lose an average of 5.3% grey matter per year compared to a loss of only 0.9% in the healthy volunteers.

In the future, such images may offer researchers a potent tool for assessing the impact of therapies on dementia as well as for evaluating the spread of the disease.

Is it possible that virtual reality--the stuff of Matrix movies and futuristic fantasy--helps elderly stroke survivors along the road to recovery? Researchers from the University of Toronto think it's a question worth investigating, and have already begun a pilot study of stroke survivors 60 years and older to explore the possible benefits of this immersive, interactive, 3-D computer experience.

Theoretically, the researchers explain, virtual reality can encourage competence, expression and pleasure in leisure activities in older stroke survivors. They believe that virtual reality has the potential to offer people with disabilities greater control over events in their environment, thereby contributing to a sense of competence and satisfaction with life.

How might this be possible? The Mandala® Gesture Xtreme virtual reality system uses a video camera as a capturing and tracking device to give the user the sense of being immersed in the virtual environment. The user sees herself on a television screen while the virtual reality system responds to her movements. The user does not have to wear, touch or hold anything, making this system especially ideal for the disabled elderly. By means of the system's video gesture capability, the user's movements (reaching, bending) trigger visible or invisible icons to score points and manipulate animations, such as playing a virtual drum kit.

One concept the investigators use to illustrate how disabled elderly interact with and may benefit from virtual environments is entexturing--the awareness of the body with respect to a variety of sensory stimuli (space, light, colour, sound) and the regulation of activity surrounding the body in order to produce a finely articulated and satisfying whole. In the virtual environment shown here, the user was required to reach out to the sides and across her body to hit the various drums placed around her. By hitting the drums, the user is executing an activity by responding to auditory and visual stimuli, creating a rhythm and expressing creativity.

The use of virtual reality, according to the investigators, can be a positive addition to the lives of people recovering from stroke. Although they will be focusing on the social and psychological benefits of virtual reality, the potential physical gains, such as improved balance and range of motion, merit exploration as well.

Margda Wærn, MD, PhD, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg, Sweden.

Seniors who commit suicide often consult their doctors a short time before they take their lives, but few communicate their suicide intent. Rather, they may focus on somatic complaints. This paper reviews the literature on the connection between physical illness and suicide. Recent research shows that over half of those who commit suicide late in life suffer from serious physical illness or impairment. The association between physical illness and suicide may be stronger in men than in women. Since most physically ill persons who commit suicide suffer from depression, depression should be treated aggressively in seniors with concomitant physical disorders.
Key words: suicide, suicide attempts, physical illness, depression, elderly.

Ron Keren, MD, FRCPC, Clinical Director, University Health Network and Whitby Mental Health Centre Memory Clinics; Assistant Professor, University of Toronto, Toronto, ON.

In recent years, a number of observational studies have shown that when consumed in moderation, alcohol may contribute to healthy living, reducing the risks of both coronary artery disease and dementia. While the ill effects of excessive drinking on cognition have been extensively described, there are no clinical or pathological consensus criteria defining alcohol-induced dementia. In fact, its existence as a distinct entity is controversial. More research on the effects of alcohol on the brain is needed in order to advise patients on the potential risks and benefits of alcohol consumption.
Key words: alcohol consumption, dementia, prevention, cognition, Wernicke-Korsakoff.

Rory H. Fisher, MB, FRCP(Ed)(C), Director, The Regional Geriatric Program of Toronto and Interdepartmental Division of Geriatrics, Faculty of Medicine, University of Toronto, Toronto, ON.

The impact of the Romanow Report on the elderly is reviewed here. Recommendations for a Health Council, modernization of the Canada Health Act, improved home care and a National Drug Agency would benefit all elderly Canadians. However, the current unmet needs of the elderly, the value of specialized geriatric services and the developments in other jurisdictions are not recognized. The Romanow Commission fails senior citizens by ignoring their current unmet needs.
Key words: Romanow Report, recommendations, elderly.