Deficits in acquisition and retention of new information, two core features of early Alzheimer disease (AD), are generally observed before the clinical onset of dementia. Mild cognitive impairment (MCI) is a descriptive term that has been used to describe the transitional or borderline state between normal aging and onset of Alzheimer disease. Earlier identification and treatment of MCI is of urgent clinical interest since the elderly are the fastest growing segment of the U.S. population, and approximately 12-15 percent of MCI cases convert to AD each year. This pilot-project is a functional MRI (fMRI) study of learning and forgetting in normal aging and MCI. With recent advances in the cognitive neuroscience of memory and statistical processing of functional images, it is now possible to detect dynamic changes in neural activation associated with the acquisition and retention of new information. In this pilot project, we propose to study 15 MCI and 15 demographically matched healthy, cognitively normal adults between ages 60 and 85 with an event- related verbal learning paradigm during fMRI scanning. Subjects will also receive neuropyschological testing with emphasis on aspects of memory.
Specific Aims : 1. Characterize the neural response during learning of temporally spaced, repeating information in MCI and healthy controls. We expect that in normal controls activations associated with repeated exposure will decrease over time, a phenomenon known as repetition suppression or adaptation; this 'learning' effect will be evident in the left anterior hippocampus. In contrast, MCI patients will not show this effect-thus, each word will be perceived as novel despite repeated presentation. The learning effect will be assessed with linear as well as exponential models of adaptation. 2. Neuropsychological functioning (verbal memory scores) will be related to activation in the MCI group: Greater severity of psychometric memory deficit will be related to less adaptation within the hippocampus. Once patterns of activation are established in MCI and controls, longitudinal designs can be implemented and other patient groups such as those with depression and various forms of mild dementia can be investigated. Thus, we expect that the results from this pilot grant will be useful in guiding hypotheses for future funded experiments that further our understanding of the neural substrates of memory and its breakdown in MCI and related disorders. Such knowledge may be useful in identifying subjects at risk for AD for earlier intervention as treatments become available.
| Johnson, Sterling C; Baxter, Leslie C; Susskind-Wilder, Lana et al. (2004) Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment. Neuropsychologia 42:980-9 |
| Johnson, Sterling C; Baxter, Leslie C; Wilder, Lana S et al. (2002) Neural correlates of self-reflection. Brain 125:1808-14 |
