This project, entitled """"""""Mapping Early Network Dysfunction in FTD and AD"""""""" will develop novel network connectivity analyses with the goal of improving early detection and diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD). Normal cognitive and behavioral functions require coordinated activity, within large-scale, distributed networks. Emerging data from human studies and animal disease models suggest that specific networks may develop early, tell-tale aberrations during incipient neurodegenerative disease. To explore this possibility, we will use functional connectivity MRI (fcMRI) and diffusion spectral imaging (DSI) to study 60 patients with FTD, 20 asymptomatic FTD gene mutation carriers, 15 patients with AD, and 30 healthy controls. We hypothesize that network connectivity mapping will link each clinical syndrome to a specific intrinsic brain network, will prove capable of detecting early disease, and will provide new insights into symptom pathogenesis.
Our aims are (1) to detect network alterations in early stage FTD and AD, (2) to compare the ability of fcMRI, DSI, and conventional structural MRI to detect network-level dysfunction in presymptomatic FTD gene mutation carriers, and (3) to correlate FTD and AD symptoms with network connectivity disruption. The knowledge gained could provide a first step toward a novel, non- invasive imaging biomarker for early FTD and AD and clarify the network basis for FTD, AD, and other neuropsychiatric disorders that target the brain at the network level.

Public Health Relevance

This project will investigate the specific brain networks disrupted in frontemporal dementia and Alzheimer's disease. The goal of the research is to use neuroimaging to clarify where in the brain these diseases begin and how network dysfunction leads to symptoms. Further developed, these methods could improve early detection and diagnosis and provide a sensitive biomarker for following the effects of treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG023501-09
Application #
8375367
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2012-04-15
Budget End
2013-03-31
Support Year
9
Fiscal Year
2012
Total Cost
$152,711
Indirect Cost
$56,111
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Burette, Alain C; Judson, Matthew C; Li, Alissa N et al. (2018) Subcellular organization of UBE3A in human cerebral cortex. Mol Autism 9:54
Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M et al. (2018) Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging. J Neurosci 38:530-543
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
Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M et al. (2018) A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. J Alzheimers Dis 63:1347-1360
Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642
Vatsavayai, Sarat C; Nana, Alissa L; Yokoyama, Jennifer S et al. (2018) C9orf72-FTD/ALS pathogenesis: evidence from human neuropathological studies. Acta Neuropathol :
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
Brent, Robert J (2018) Estimating the monetary benefits of medicare eligibility for reducing the symptoms of dementia. Appl Econ 50:6327-6340
Miller, Zachary A; Rosenberg, Lynne; Santos-Santos, Miguel A et al. (2018) Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy. JAMA Neurol 75:728-737
Ossenkoppele, Rik; Rabinovici, Gil D; Smith, Ruben et al. (2018) Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 320:1151-1162

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