This application combines cutting-edge clinical phenotyping, imaging, pathology, and genetics to move the FID and dementia field forward. With this renewal we will test and, if indicated, modify new international research criteria for bvFTD and PPA developed in this PPG, and determine the added value of imaging and other biomarkers for diagnosis. While establishing parameters for recognizing bvFTD, PPA, CBS, and PSPS patients with AD versus FTLD pathology, we will improve antemortem recognition of molecular subtypes that are associated with FID, CBS, and PSP-S. Imaging is a focus in renewal, and multimodality imaging and ICN fMRI will be used to detect early changes in FTD and facilitate diagnosis. We believe that identifying molecular subtypes in vivo will be improved by the use of biomarkers from CSF and genetics. These new approaches come at a time when preventive and disease-modifying clinical trials are beginning in FTD and related disorders, trials that will require knowledge of the underlying molecular etiology for each clinical syndrome. While improving differential diagnosis, we hope to further understanding of the puzzling and troubling socio-emotional, executive control, and language problems that occur with FTD. In our first eight years we developed new cognitive and emotional tasks in Core A and in Dr. Levenson's Emotion Project 3. In Project 4, Drs. Miller and Gorno-Tempini employed novel and sophisticated approaches to studying different components of behavior in bvFTD and language in PPA. Project 5 developed tasks that probe executive control and self-awareness. We will continue to study these tasks for their underlying anatomy and diagnostic value. Beyond their relevance to patients with dementia, the tasks used in the PPG offer a new way to probe conditions with anatomy that overlaps with FTD, including autism, attention deficit disorder, schizophrenia, bipolar illness, obsessive-compulsive disorder and dyslexia.

Public Health Relevance

The Program will benefit the public health by advancing the understanding of front temporal dementia and identify the best diagnostic tools and potentially uncover treatment targets. If successful, this work could accelerate the search for new therapies for prevalent age-related neurodegnerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG019724-11
Application #
8214827
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (02))
Program Officer
Hsiao, John
Project Start
2001-07-01
Project End
2017-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
11
Fiscal Year
2012
Total Cost
$1,959,873
Indirect Cost
$607,509
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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