Semin Neurol 2019; 39(02): 251-263
DOI: 10.1055/s-0039-1683379
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Frontotemporal Dementia: A Clinical Review

Harri Sivasathiaseelan
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Charles R. Marshall
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
2  Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
,
Jennifer L. Agustus
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Elia Benhamou
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Rebecca L. Bond
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Janneke E. P. van Leeuwen
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Chris J. D. Hardy
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Jonathan D. Rohrer
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
,
Jason D. Warren
1  Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
29 March 2019 (online)

Abstract

Frontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as “molecular nexopathies,” a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Mutations in three major genes collectively account for a substantial proportion of behavioral presentations, with far-reaching implications for the lives of families but also potential opportunities for presymptomatic diagnosis and intervention. Predicting molecular pathology from clinical and radiological phenotypes remains challenging; however, certain patterns have been identified, and genetically mediated forms of frontotemporal dementia have spearheaded this enterprise. Here we present a clinical roadmap for diagnosis and assessment of the frontotemporal dementias, motivated by our emerging understanding of the mechanisms by which pathogenic protein effects at the cellular level translate to abnormal neural network physiology and ultimately, complex clinical symptoms. We conclude by outlining principles of management and prospects for disease modification.