期刊
NEURODEGENERATIVE DISEASES
卷 9, 期 4, 页码 176-186出版社
KARGER
DOI: 10.1159/000335876
关键词
Functional MRI; Clinical trial; Episodic memory; Biomarker; Dementia
资金
- NIA National Institute on Aging [K23 AG027171, RO1 AG027435]
- Harvard-Massachusetts Institute of Technology Health Sciences & Technology Pfizer-Merck
- NIH National Institutes of Health
- Forest Pharmaceuticals
- Harvard Center for Neurodegeneration Repair
- Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (NIA National Institute on Aging) [P50 AG05134]
- Geriatric Research, Education and Clinical Center (GRECC) at the Edith Nourse Rogers Memorial (ENRM) Veterans Administration (VA) Bedford Medical Center
- Forest Research Institute
- Eisai Pharmaceuticals
- Forest Pharmaceuticals Inc.
- H. Lundbeck A/S
- Merck Co Inc.
- Merz Pharmaceuticals
- Novartis AG
- Elan
- Pfizer
- Bristol-Myers-Squibb
- NIH/NIA [K23, R01, P50]
Background: Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown. Objective: To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months. Methods: Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT). Results: Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus. Conclusion: Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies. Copyright (C) 2012 S. Karger AG, Basel
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