Tiffany W. Chow, MD, MSc, Baycrest Health Sciences Rotman Research Institute, and Ross Memory Clinic; University of Toronto Depts. of Medicine (Neurology Division) and Psychiatry (Geriatric Psychiatry Division).

Abstract
Much of the published clinical research in dementia has focused on diagnostic biomarkers and neuroimaging analyses that are not yet validated for routine clinical practice or on unsuccessful clinical drug trials. Primary care providers can nonetheless make a significant difference in the management of patients with dementia and their families, based on appropriate referrals of non-Alzheimer's dementia cases to specialists and supporting informal caregivers.
Frontotemporal degeneration, a non-Alzheimer's dementia that strikes in the 6th decade of life, provides many opportunities for the entire healthcare team to educate and back families up through a harrowing neurodegenerative illness. This paper is intended to highlight for primary care physicians what can be done and how to accomplish it through a team approach. Some concepts, such as a switch from medicalized views of "behavioural and psychiatric symptoms of dementia" to "Responsive Behaviours" can be generalized across dementia etiologies, but the age at onset and marked social disability and dysfunction caused by frontotemporal degeneration warrant some additional guidelines to assure the safety and highest quality of life possible for the patient and those around him. In particular, refitting a day program to accommodate clients with frontotemporal degeneration and attending to the needs of children who find themselves in informal caregiver roles are addressed.
Keywords: caregiver, dementia, frontotemporal dementia, primary progressive aphasia.

Simone Pomati, MD, PhD, Centre for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, Luigi Sacco Hospital, Milan, Italy.
Francesca Clerici, MD, PhD, Centre for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, Luigi Sacco Hospital, Milan, Italy.
Stefano Defendi, MD, Centre for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, Luigi Sacco Hospital, Milan, Italy.
Silvia Bovo, MD, Centre for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, Luigi Sacco Hospital, Milan, Italy.
Claudio Mariani, MD, Chair of Clinical Neurology, University of Milan; Centre for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, Luigi Sacco Hospital, Milan, Italy.

Frontotemporal dementia (FTD) is a progressive condition characterized by atrophy of the frontal and/or temporal lobes. Three main clinical syndromes have been described (behavioural variant, progressive nonfluent aphasia, and semantic dementia). The symptoms reflect the anatomical distribution of the pathological changes rather than the precise histological subtype. Frontotemporal dementia is a genetically complex disorder with a strong likelihood of inheritance, mainly transmitted as an autosomal dominant trait. Mutations in microtubule associated tau protein and progranulin have been reported in several families affected by FTD. The treatment is directed to the control of the behavioural disturbances through pharmacological and nonpharmacological approaches.
Key words: frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, neuropsychology, progranulin.

Weerasak Muangpaisan, MD, FRCPT, Assistant Professor, Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand; visiting fellow, Harris Manchester College, University of Oxford, Oxford, U.K.

Cases of dementia are increasing due to longer life expectancy of the world population. Physicians should be able to recognize common dementia syndromes. After excluding reversible causes of dementia, there are four common dementia syndromes, which are Alzheimer’s disease, vascular dementia, dementia with Lewy body, and frontotemporal dementia. The key points of clinical differences of these dementia syndromes are summarized in this article.
Key words: Alzheimer’s disease, vascular dementia, dementia with Lewy body, frontotemporal dementia, Parkinson’s disease.

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.

Lan Xiong, MD, PhD, CHUM Research Centre, Notre-Dame Hospital, Montréal Hospital, Montréal, QC.
Claudia Gaspar, PhD, CHUM Research Centre, Notre-Dame Hospital, Montréal Hospital, Montréal, QC.
Guy A. Rouleau, MD, PhD, FRCPC, CHUM Research Centre, Notre-Dame Hospital, Montréal Hospital, Montréal, QC.

Both Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are genetically complex and heterogeneous disorders. Although fully penetrant (causal) mutations leading to predominantly familial early onset AD have been identified in three genes (APP, PSEN1, and PSEN2), they only account for a small fraction of AD patients. PSEN1 is considered the most frequently mutated gene in early onset AD. Mutations in the microtubule-associated protein tau (MAPT) gene have been reported in up to 50% of hereditary cases of FTD. One partially penetrant genetic risk factor (APOE4) has been established for the more common late-onset form of AD. Despite advances in elucidating the genetic epidemiology of AD and FTD, the etiology for most patients with dementia remains unclear.

Key words: Alzheimer’s disease, frontotemporal dementia, genetics, linkage, mutation.

Andrew Kertesz, MD, FRCP(C), Director of Cognitive Neurology, St. Joseph’s Health Center, University of Western Ontario, London, ON.
David Munoz, MD, FRCP(C), Department of Pathology, St. Michael’s Hospital, University of Toronto, Toronto, ON.

Frontotemporal dementia (FTD or Pick’s disease) is a relatively common but underdiagnosed form of presenile dementia. Estimated prevalence is 20% of dementias and 50% of dementia in patients under age 65. Common presentations are disinhibition with indifference; progressive aphasia; semantic dementia; unexplained falls, vertical gaze palsy, and dysarthria; and dementia with motor neuron disease. Neuroimaging is essential to exclude a slow tumour. Tau mutations are found in some families. Atypical neuroleptics and antidepressants can effectively treat some of the characteristics of FTD.

Key words: frontotemporal dementia, Pick’s disease, primary progressive aphasia, corticobasal degeneration, progressive supranuclear palsy.