The overall long-term goal of this project is to assess the value of multimodality imaging for (1) differential diagnosis and early detection of FTD subtypes and related disorders, (2) for understanding the changes in the brain responsible for cognitive, linguistic, and emotional dysfunction in FTD and AD, and (3) to predict longitudinal changes in cognition and function in FTD. These goals will be accomplished by utilizing an integrated processing framework for multimodality neuroimages as well as modern multivariate statistical methods that allow simultaneous testing of variations across image modalities and across brain regions for maximally exploiting information from multimodality brain images.
Specific Aims are to: (1) Use multimodality neuroimaging to distinguish those subjects with non-AD clinical syndromes caused by Alzheimer's amyloid pathology from those without amyloid pathology. We hypothesize that although the changes of sMRI will be the dominant imaging features for differential diagnosis at later stages of disease, adding ASL, DTI, ICN fMRI, FDG PET will improve single subject prediction of subjects with FTD clinical syndromes associated with amyloid pathology determined by PIB imaging versus those associated with other pathologies. (2) Explore the brain-behaviour association of multimodality neuroimaging for the following cognitive and behavioral profiles: (a) motor speech impairment, (b) executive control, and (c) emotion. (3) Explore the predictive value of baseline brain-behavior associations for longitudinal decline and identify a combination of multimodality brain-behavior associations that best predicts the decline. The predictors will be various brain regions in the different imaging modalities and the outcomes will be the rate of change of cognitive function measured by CDR sum of boxes. The innovative nature of this project is the use of multimodality-multivariate analysis methods to investigate FTD and related neurodegenerative diseases. The long term significance of this project is that as these methods are developed, they will be used to explore improved methods for early detection, diagnosis, and monitoring of change, and ultimately will lead to improved patient assessment and development of improved treatments.

Public Health Relevance

The relevance of this project is that it will provide improved measures of changes in the brain in Frontotemporal dementia which will improve diagnosis, early detection, and clinical treatment trials of this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG019724-12
Application #
8531790
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
12
Fiscal Year
2013
Total Cost
$120,899
Indirect Cost
$56,553
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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

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