Almost all Alzheimer's disease (AD) patients eventually develop anomia. Recent literature indicates that such word-finding problems are not monolithic. Lexical and semantic deficits can exist independently in AD patients, and both can impair word finding. The long-term goal of this R21 application is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in AD. Sixteen AD patients with lexical deficits, 16 AD patients with semantic deficits, and 16 normal controls will perform a picture naming task during functional MRI (fMRI), and activity from each group will be compared to activity from each other group in voxelwise t-test images. Main hypotheses are: (1) Patients with lexical deficits will demonstrate decreased activity relative to normal controls in left perisylvian regions that support lexical functions. (2) Patients with semantic deficits will show decreased activity relative to normal controls in both left inferior temporal cortex supporting semantic functions and left perisylvian cortex supporting lexical functions. Activity decrease in perisylvian cortex is expected not because of underlying neuropathology, but because this cortex is not adequately stimulated by semantic input from inferior temporal cortex. In post hoc analyses, activity in frontal cortex also will be examined to determine if the AD groups demonstrate compensatory activity increases in different frontal regions. Further, functional activity in the left inferior temporal and posterior perisylvian cortices will be correlated with measures of semantic and lexical deficits to determine if this activity correlates with these two impairments, respectively. In addition, structural images from the different groups will be compared using voxel-based morphometry (VBM) to assess regional differences in gray matter atrophy. It is expected that AD patients with lexical deficits will show the greatest atrophic changes relative to controls in left perisylvian cortex, and AD patients with semantic deficits will show the greatest atrophic changes relative to controls in left inferior temporal cortex. Finally, correlation images between fMRI signal intensities from picture naming and VBM intensities from anatomic images will be generated. It is expected that fMRI activity decreases in the left inferior temporal cortex during naming will correlate with degree of atrophy in this region in a combined analysis of all subject groups; however, according to the proposed model, fMRI activity decreases in the left perisylvian cortex will correlate with atrophy in that region only for the lexical deficit group and not for a combined analysis of all subjects. Once these different patterns of deficit are understood, interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease will improve quality of life for patients and families and will prolong independence, thereby delayin institutionalization and decreasing costs.

Public Health Relevance

The long-term goal of the proposed research is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in Alzheimer's disease. Once these different patterns of deficit are understood, different interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease process will improve quality of life for patients and their families and will prolong their independence, thereby reducing the need for institutionalization and decreasing health care costs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DC009247-03
Application #
8508024
Study Section
Language and Communication Study Section (LCOM)
Project Start
2009-09-01
Project End
2013-09-30
Budget Start
2012-07-01
Budget End
2013-09-30
Support Year
3
Fiscal Year
2010
Total Cost
$74,298
Indirect Cost
Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Crosson, Bruce (2013) Thalamic mechanisms in language: a reconsideration based on recent findings and concepts. Brain Lang 126:73-88
Meinzer, Marcus; Beeson, PĂ©lagie M; Cappa, Stefano et al. (2013) Neuroimaging in aphasia treatment research: consensus and practical guidelines for data analysis. Neuroimage 73:215-24
Meinzer, Marcus; Rodriguez, Amy D; Gonzalez Rothi, Leslie J (2012) First decade of research on constrained-induced treatment approaches for aphasia rehabilitation. Arch Phys Med Rehabil 93:S35-45
FitzGerald, David B; Crosson, Bruce A (2011) Diffusion weighted imaging and neuropsychological correlates in adults with mild traumatic brain injury. Int J Psychophysiol 82:79-85
Crosson, Bruce; Ford, Anastasia; McGregor, Keith M et al. (2010) Functional imaging and related techniques: an introduction for rehabilitation researchers. J Rehabil Res Dev 47:vii-xxxiv