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
Naasan, Georges; Rabinovici, Gil D; Ghosh, Pia et al. (2016) Amyloid in dementia associated with familial FTLD: not an innocent bystander. Neurocase 22:76-83
Barton, Cynthia; Ketelle, Robin; Merrilees, Jennifer et al. (2016) Non-pharmacological Management of Behavioral Symptoms in Frontotemporal and Other Dementias. Curr Neurol Neurosci Rep 16:14
Ranasinghe, Kamalini G; Rankin, Katherine P; Pressman, Peter S et al. (2016) Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration. JAMA Neurol 73:1078-88
Yokoyama, Jennifer S; Marx, Gabe; Brown, Jesse A et al. (2016) Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav :
Vatsavayai, Sarat C; Yoon, Soo Jin; Gardner, Raquel C et al. (2016) Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia. Brain 139:3202-3216
Schott, Jonathan M; Crutch, Sebastian J; Carrasquillo, Minerva M et al. (2016) Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease. Alzheimers Dement 12:862-71
Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L et al. (2016) Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease. Brain 139:2528-39
Mair, Waltraud; Muntel, Jan; Tepper, Katharina et al. (2016) FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease. Anal Chem 88:3704-14
Silva, M Catarina; Cheng, Chialin; Mair, Waltraud et al. (2016) Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability. Stem Cell Reports 7:325-40
Nascimento, Camila; Suemoto, Claudia K; Rodriguez, Roberta D et al. (2016) Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample. Brain Pathol 26:177-85

Showing the most recent 10 out of 497 publications