The purpose of this study is to examine different etiologies and cognitive profiles of mild cognitive impairment (MCI), a clinical characterization originally defined to identify individuals in the preclinical phase of Alzheimer's Disease (AD). It is now clear that a large portion of individuals with MCI do not progress to AD, thus understanding MCI becomes a more general problem for the aging population. We propose that hippocampal dysfunction and vascular disease are two possible etiologies of MCI that may lead to different cognitive profiles of MCI. It is possible that the episodic memory deficit used to classify MCI is, in some cases, a secondary effect of deficits in working memory. There is some evidence that white matter signal hyperintensities (WMH), an indication of cerebrovascular disease, are correlated with deficits in working memory. Thus, we predict that individuals with MCI and high WMH will have deficits in working memory that lead to deficits in episodic memory Using hippocampal atrophy as a marker for hippocampal dysfunction, we predict that individuals with MCI and hippocampal atrophy will show classic episodic memory deficits with normal working memory. We will also examine the mechanisms of memory impairments in these groups of individuals with MCI by using fMRI to compare patterns of brain activity during performance on working memory and episodic memory tasks. We predict that MCI individuals with WMH will show reduced activation in the dorsolateral prefrontal cortex, an area known to be involved in working memory, during performance on a working memory task. In contrast, we predict MCI individuals with hippocampal atrophy will show reduced hippocampal activation during performance on an episodic memory task.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31MH065082-01A1
Application #
6552038
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Curvey, Mary F
Project Start
2002-08-01
Project End
2005-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$25,047
Indirect Cost
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Nordahl, Christine Wu; Ranganath, Charan; Yonelinas, Andrew P et al. (2006) White matter changes compromise prefrontal cortex function in healthy elderly individuals. J Cogn Neurosci 18:418-29