Chris MacKnight, MD, MSc, FRCPC, Associate Professor, Department of Medicine, Dalhousie University, Halifax, NS.

Three cholinesterase inhibitors are available in Canada for the treatment of mild and moderate Alzheimer’s disease. As the three agents differ in their pharmacology, switching among them does sometimes make sense. Switching may be necessary because of intolerance, lack of response, and occasionally loss of response. This article will describe how and when to switch cholinesterase inhibitor.
Key words: Alzheimer’s disease, treatment response, cholinesterase inhibitors, switching, dementia.

David F. Tang-Wai, MDCM, FRCPC, Assistant Professor, University of Toronto; Division of Neurology, University Health Network Memory Clinic, Toronto Western Hospital, Toronto, ON.

Alzheimer’s disease is the most common cause of dementia among older adults. After a century of research, there have been significant scientific advances in the understanding of this disorder. Over the past 15 years, treatment for Alzheimer’s disease exists but it is symptomatic and its effects are modest at best. Currently, newer disease-modifying treatments are being investigated that have the potential of slowing the progression of the disease.
Key words: Alzheimer’s disease, disease-modifying agents, amyloid, tau, neuroprotection.

Elise J. Levinoff, MSc, BSc, University of Ottawa, Faculty of Medicine, Ottawa, ON.

Dementia is a neurological disease that is associated with aging. The incidence and prevalence of dementia is increasing as the population continues to age. The two most common forms of dementia are Alzheimer’s disease (AD) and vascular dementia (VaD). Although these two forms of dementia represent different pathologies and different clinical presentations, they share similar risk factors. It is important to distinguish between the two forms of dementia because of the differing treatments, and because the risk factors for each are often preventable. This article will discuss the classification, risk factors, and diagnosis of AD and VaD, and present distinguishing characteristics between them.
Key words: dementia, Alzheimer’s disease, vascular dementia, stroke, memory.

Yosuke Wakutani, MD, Centre for Research in Neurodegenerative Diseases, Departments of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, ON.
Peter St. George-Hyslop, MD, Centre for Research in Neurodegenerative Diseases, Departments of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, ON.
Ekaterina Rogaeva, PhD, Centre for Research in Neurodegenerative Diseases, Departments of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, ON.

There are ~200 human diagnostic categories presenting as or accompanying dementia (interested readers may investigate the database Online Mendelian Inheritance in Man, a catalog of human genes and genetic disorders, at www.ncbi.nlm.nih.gov/ genome/guide/human/). Many forms of dementia are associated with deposition of different aberrant proteins in the brain. Familial aggregation in Alzheimer’s disease (AD), frontotemporal dementia (FTD), and other forms of dementia implies the presence of inherited susceptibility factors. Many forms of dementia remain genetically unexplained; however, linkage analyses suggest that most of them are complex disorders with several underlying genetic factors. Here we provide an update on known genes responsible for dementia with the strongest focus on AD and FTD, which are the most common forms of dementia.
Key words: dementia, Alzheimer’s disease, gene, APP, APOE, frontotemporal dementia.

D. Larry Sparks, PhD, Senior Scientist and Head, Roberts Laboratory for Neurodegenerative Disease Research, Sun Health Research Institute, Sun City, AZ, USA.

The primary care physician is often pressed with first-line treatment of Alzheimer’s disease (AD). A number of FDA-approved therapies are available. Emerging data indicate that circulating cholesterol levels may influence progression of the dementing disorder. A recent pilot, proof-of-concept, placebo-controlled clinical trial suggests that the cholesterol-lowering medication atorva-statin provides benefit in treating mild-to-moderate AD. Although not approved for the treatment of AD, statin therapy might be considered in the setting of elevated cholesterol levels--even when LDL/HDL ratios are acceptable.
Key words: Alzheimer’s disease, cholesterol, statins, dementia, atorvastatin.

Andrew R. Frank, MD, Alzheimer’s Disease Center, Mayo Clinic College of Medicine, Rochester, MN, U.S.A.
Ronald C. Petersen, MD, PhD, Alzheimer’s Disease Center, Mayo Clinic College of Medicine, Rochester, MN, U.S.A.

Mild Cognitive Impairment (MCI) describes a state of abnormal cognitive functioning that is insufficient to warrant a diagnosis of dementia. While dementia requires that activities of daily functioning be compromised due to cognitive symptomology, the diagnosis of MCI can be made earlier, in the absence of such functional impairment. In MCI, the patient must present with cognitive complaints (or someone who knows the patient well must present them on the patient's behalf), and these complaints must be corroborated by abnormalities on standardized cognitive testing. The diagnosis of MCI alerts the clinician to a higher risk of future development of dementia and provides an ideal target population that may benefit the most from “disease-modifying” cognitive therapies currently in development.
Key words: mild cognitive impairment, MCI, Alzheimer’s disease, dementia, early diagnosis, treatment.

Emerging drug therapies for dementia are increasingly chosen to tackle molecular targets important in Alzheimer’s disease (AD) pathobiology. Amyloid oligomers, amyloid deposits, and neurofibrillary tangles (NFTs) are characteristic findings in AD. Hence, drugs that interfere with these proteinaceous aggregates are receiving the most attention: a) alpha, beta, and gamma secretase modulators, b) inhibitors of amyloid beta (Ab) aggregation, and c) anti-Ab immunologic strategies. Oxidative stress and inflammatory reactions appear part of a loop of neurotoxicity with the proteinacous aggregates. Antioxidants and anti-inflammatory compounds have thus received much attention. Finally, other compounds may work by a variety of other mechanisms.
Key words: Alzheimer’s disease, amyloid, secretase inhibitors, antioxidants, anti-inflammatory agents.

The accredited CME learning activity based on this article is offered under the auspices of the CE department of the University of Toronto. Participating physicians are entitled to one (1) MAINPRO-M1 credit by completing this program, found online at www.geriatricsandaging.ca/cme

Lonn Myronuk, MD, FRCPC, Member of the Canadian Academy of Geriatric Psychiatry; President, GeriPsych Medical Services, Inc., Parksville, BC.

Progress in basic neuroscience has brought disparate clinical phenotypes of dementia together in categories based on common pathophysiological processes. Degenerative dementias are all proteinopathies featuring abnormal processing and CNS accumulation of different proteins in different neuroanatomic distributions dictating patterns of presentation of clinical symptoms and potential responsiveness to treatment. Alzheimer’s disease (AD) is an amyloidopathy. Dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and multiple system atrophy (MSA) are synucleinopathies. Frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy, and corticobasal degeneration are tauopathies. Vascular dementia (VaD) has been considered a distinct pathophysiologic process yet may exist on a continuum with AD. Currently available dementia treatments are not specific for a single disorder, yet not all dementias are treatment responsive. Exclusion of otherwise treatable depressive disorders and metabolic derangements as well as surveillance for deleterious cognitive effects of medication remain central to the assessment and treatment of the older adult with cognitive complaints. Identification of those syndromes for which certain medications may be contraindicated, as well as those that may be selectively responsive to particular compounds, will continue to increase in importance as our range of therapeutic options widens over the coming years.
Key Words: Alzheimer’s disease, Lewy body, frontotemporal lobar degeneration, vascular dementia, differential diagnosis.

Ging-Yuek Robin Hsiung, MD, MHSc, FRCPC, Assistant Professor, Division of Neurology, Department of Medicine, UBC Clinic for Alzheimer Disease & Related Dementias, University of British Columbia, Vancouver, BC.

Dementia care represents a significant burden to our society. Although we are still far from any cure for dementia, there are several medications available for symptomatic management of Alzheimer’s disease and vascular dementia. These agents not only improve the cognitive and behavioural symptoms of dementia but may also help maintain patients’ functional independence and lessen caregiver stress. There are also a number of clinical trials currently in place to investigate new agents for treatment of Alzheimer’s disease. This article reviews the current medications available for Alzheimer’s disease and vascular dementia, as well as a number of promising agents that are under investigation.
Key words: Alzheimer’s disease, vascular dementia, cholinesterase inhibitors, donepezil, galantamine, rivastigmine, memantine.

Raj C. Shah, MD, Rush Alzheimer’s Disease Center; Department of Family Medicine, Rush University Medical Center, Chicago, IL, USA.
David A. Bennett, MD, Rush Alzheimer’s Disease Center; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

Mild cognitive impairment (MCI), the presence of cognitive difficulties without having dementia, is viewed as a preclinical state for Alzheimer’s disease (AD) or another dementing illness. With the burden of AD expected to increase, research efforts have focused on interventions to delay the progression of MCI to AD. In this review, we first discuss the current conceptual understanding of MCI. Then, we outline a simplified approach to help clinicians diagnose MCI. Finally, we provide an overview of how to address the clinical needs of individuals with MCI.
Key words: mild cognitive impairment, Alzheimer’s disease, diagnosis, prognosis, treatment.