The long-term objective of this project is to understand the changes in brain and cognitive function that take place before the onset of the clinical symptoms of Alzheimer's disease. Mild cognitive impairment (MCI) is a diagnostic term describing elderly individuals with an isolated episodic memory deficit that is often a transition state between normal aging and Alzheimer's disease (AD). Thus, the study of MCI offers insight into the changes in brain and cognitive function that occur before the widespread cognitive deficits of Alzheimer's disease are present. Neuropathological studies suggest that the degree of neuropathology in the neo-cortex is likely to be a critical difference between MCI and AD. The proposed experiments will evaluate neo-cortical function in MCI using psychological and neurophysiological methods by (1) assessing basic cognitive processes thought to reflect neo-cortical function, and (2) measuring cortical potentials directly, using non-invasive event-related potentials.
The Specific Aims are: (1) to test the hypothesis that elementary cognitive functions (processing speed, attention) are impaired in MCI, (2) to test the hypothesis that cortical interactions between prefrontal cortex and sensory cortices are compromised in MCI, and (3) to determine if brain activity and behavioral measures can predict subsequent conversion to AD in individual MCI subjects, using a longitudinal study design. The proposed experiments are important because they will advance our understanding of the brain and cognitive changes that accompany the development of Alzheimer's disease. Experimental findings may also have clinical applications for determining the risk of conversion from MCI to Alzheimer's disease in individual MCI patients, and could provide objective measures of treatment efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG019681-01A1
Application #
6542992
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Buckholtz, Neil
Project Start
2002-09-15
Project End
2006-08-31
Budget Start
2002-09-15
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$256,113
Indirect Cost
Name
University of California Irvine
Department
Neurology
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Irimajiri, Rie; Golob, Edward J; Starr, Arnold (2010) ApoE genotype and abnormal auditory cortical potentials in healthy older females. Neurobiol Aging 31:1799-804
Golob, E J; Ringman, J M; Irimajiri, R et al. (2009) Cortical event-related potentials in preclinical familial Alzheimer disease. Neurology 73:1649-55
Irimajiri, Rie; Michalewski, Henry J; Golob, Edward J et al. (2007) Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment. Brain Res 1145:108-16
Golob, Edward J; Irimajiri, Rie; Starr, Arnold (2007) Auditory cortical activity in amnestic mild cognitive impairment: relationship to subtype and conversion to dementia. Brain 130:740-52
Wang, Huali; Golob, Edward J; Su, Min-Ying (2006) Vascular volume and blood-brain barrier permeability measured by dynamic contrast enhanced MRI in hippocampus and cerebellum of patients with MCI and normal controls. J Magn Reson Imaging 24:695-700
Ray, Kimberly M; Wang, Huali; Chu, Yong et al. (2006) Mild cognitive impairment: apparent diffusion coefficient in regional gray matter and white matter structures. Radiology 241:197-205
Bennett, Ilana J; Golob, Edward J; Parker, Elizabeth S et al. (2006) Memory evaluation in mild cognitive impairment using recall and recognition tests. J Clin Exp Neuropsychol 28:1408-22
Chen, Ya-Fang; Wang, Huali; Chu, Yong et al. (2006) Regional quantification of white matter hyperintensity in normal aging, mild cognitive impairment, and Alzheimer's disease. Dement Geriatr Cogn Disord 22:177-84
Golob, Edward J; Ovasapyan, Vahagn; Starr, Arnold (2005) Event-related potentials accompanying motor preparation and stimulus expectancy in the young, young-old and oldest-old. Neurobiol Aging 26:531-42
Irimajiri, R; Golob, E J; Starr, A (2005) Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive impairment. Clin Neurophysiol 116:1918-29

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