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 #
2P01AG019724-11
Application #
8287310
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (02))
Project Start
2012-09-01
Project End
2017-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
11
Fiscal Year
2012
Total Cost
$114,904
Indirect Cost
$41,522
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bergeron, David; Gorno-Tempini, Maria L; Rabinovici, Gil D et al. (2018) Prevalence of amyloid-? pathology in distinct variants of primary progressive aphasia. Ann Neurol 84:729-740
Björkhem, Ingemar; Patra, Kalicharan; Boxer, Adam L et al. (2018) 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome. Front Neurol 9:756
Pottier, Cyril; Zhou, Xiaolai; Perkerson 3rd, Ralph B et al. (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558
Theofilas, Panos; Ehrenberg, Alexander J; Nguy, Austin et al. (2018) Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans. Neurobiol Aging 61:1-12
Eser, Rana A; Ehrenberg, Alexander J; Petersen, Cathrine et al. (2018) Selective Vulnerability of Brainstem Nuclei in Distinct Tauopathies: A Postmortem Study. J Neuropathol Exp Neurol 77:149-161
Burette, Alain C; Judson, Matthew C; Li, Alissa N et al. (2018) Subcellular organization of UBE3A in human cerebral cortex. Mol Autism 9:54
Deleon, Jessica; Miller, Bruce L (2018) Frontotemporal dementia. Handb Clin Neurol 148:409-430
Zakrzewski, Jessica J; Datta, Samir; Scherling, Carole et al. (2018) Deficits in physiological and self-conscious emotional response to errors in hoarding disorder. Psychiatry Res 268:157-164
Rojas, Julio C; Bang, Jee; Lobach, Iryna V et al. (2018) CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP. Neurology 90:e273-e281
Hua, Alice Y; Sible, Isabel J; Perry, David C et al. (2018) Enhanced Positive Emotional Reactivity Undermines Empathy in Behavioral Variant Frontotemporal Dementia. Front Neurol 9:402

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