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
Ranasinghe, Kamalini G; Hinkley, Leighton B; Beagle, Alexander J et al. (2017) Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants. Brain 140:2737-2751
Bernier, Patrick J; Gourdeau, Christian; Carmichael, Pierre-Hugues et al. (2017) Validation and diagnostic accuracy of predictive curves for age-associated longitudinal cognitive decline in older adults. CMAJ 189:E1472-E1480
Moga, Daniela C; Abner, Erin L; Wu, Qishan et al. (2017) Bladder antimuscarinics and cognitive decline in elderly patients. Alzheimers Dement (N Y) 3:139-148
Sposato, Luciano A; Ruíz Vargas, Estefanía; Riccio, Patricia M et al. (2017) Milder Alzheimer's disease pathology in heart failure and atrial fibrillation. Alzheimers Dement 13:770-777
Sturm, Virginia E; Perry, David C; Wood, Kristie et al. (2017) Prosocial deficits in behavioral variant frontotemporal dementia relate to reward network atrophy. Brain Behav 7:e00807
Scherling, Carole S; Zakrzewski, Jessica; Datta, Samir et al. (2017) Mistakes, Too Few to Mention? Impaired Self-conscious Emotional Processing of Errors in the Behavioral Variant of Frontotemporal Dementia. Front Behav Neurosci 11:189
Sennik, Simrin; Schweizer, Tom A; Fischer, Corinne E et al. (2017) Risk Factors and Pathological Substrates Associated with Agitation/Aggression in Alzheimer's Disease: A Preliminary Study using NACC Data. J Alzheimers Dis 55:1519-1528
Fernández-Fournier, Mireya; Perry, David C; Tartaglia, Maria Carmela et al. (2017) Precipitous Deterioration of Motor Function, Cognition, and Behavior. JAMA Neurol 74:591-596
Neu, Scott C; Pa, Judy; Kukull, Walter et al. (2017) Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol 74:1178-1189
Burke, Shanna L; O'Driscoll, Janice; Alcide, Amary et al. (2017) Moderating risk of Alzheimer's disease through the use of anxiolytic agents. Int J Geriatr Psychiatry 32:1312-1321

Showing the most recent 10 out of 501 publications