Cortical Deactivation in Mild Cognitive Impairment: High-Field-Strength Functional MR Imaging

Abstract

To prospectively identify brain regions in which task-related changes in activation during a memory encoding task, measured with functional magnetic resonance (MR) imaging, correlate with degree of memory impairment across Alzheimer disease (AD), mild cognitive impairment (MCI), and elderly control subjects. The institutional review board approved this HIPAA-compliant study, and each patient gave written informed consent. Seventy-five subjects (mean age, 72.9 years+/-7.2 [standard deviation]; 37 men, 38 women)-13 patients with mild AD, 34 individuals with amnestic MCI, and 28 healthy elderly control subjects-were imaged at 4.0 T during novel encoding (NE) and familiar encoding (FE) of face-name pairs presented within a block design for later retrieval. Blood oxygen level-dependent (BOLD) changes were assessed across the entire brain for each group. Between-subject analysis identified brain regions demonstrating a monotonic increase or decrease in activation magnitude, from control subjects to patients with MCI to patients with mild AD. BOLD response was also correlated with score on the delayed portion of the California Verbal Learning Test (CVLT). In controls, the task elicited positive activation (NE>FE) in the dorsolateral prefrontal, lateral parietal, and medial temporal regions, and negative activation (FE>NE) in the midline frontal and parietal regions. Along the spectrum from control subjects to patients with AD, there was decreasing activation in the medial temporal lobe (MTL), including the hippocampus and parahippocampal and fusiform gyri, and increasing activation in the posteromedial cortices (PMCs), primarily in the precuneus and posterior cingulate gyrus. Activation magnitude in the PMCs significantly (P<.001, r=-0.502) correlated with CVLT score. Compared with activation in the MTL, deactivation in the PMCs could be a more sensitive marker of early AD at functional MR imaging.