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.
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.
|Sturm, Virginia E; Yokoyama, Jennifer S; Eckart, Janet A et al. (2015) Damage to left frontal regulatory circuits produces greater positive emotional reactivity in frontotemporal dementia. Cortex 64:55-67|
|Wagshal, Dana; Sankaranarayanan, Sethu; Guss, Valerie et al. (2015) Divergent CSF ? alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 86:244-50|
|Bloch, Lian; Haase, Claudia M; Levenson, Robert W (2014) Emotion regulation predicts marital satisfaction: more than a wives' tale. Emotion 14:130-44|
|Possin, Katherine L; LaMarre, Amanda K; Wood, Kristie A et al. (2014) Ecological validity and neuroanatomical correlates of the NIH EXAMINER executive composite score. J Int Neuropsychol Soc 20:20-8|
|Ranasinghe, Kamalini G; Hinkley, Leighton B; Beagle, Alexander J et al. (2014) Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum. Neuroimage Clin 5:385-95|
|Sanders, David W; Kaufman, Sarah K; DeVos, Sarah L et al. (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:1271-88|
|Lehmann, Manja; Ghosh, Pia M; Madison, Cindee et al. (2014) Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients. J Neurol Neurosurg Psychiatry 85:266-73|
|Sanchez-Juan, Pascual; Ghosh, Pia M; Hagen, Jayne et al. (2014) Practical utility of amyloid and FDG-PET in an academic dementia center. Neurology 82:230-8|
|Henry, Maya L; Wilson, Stephen M; Ogar, Jennifer M et al. (2014) Neuropsychological, behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: a longitudinal and post-mortem single case analysis. Neurocase 20:100-9|
|Lee, Suzee E; Khazenzon, Anna M; Trujillo, Andrew J et al. (2014) Altered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. Brain 137:3047-60|
Showing the most recent 10 out of 279 publications