Functional Connectivity of Entorhinal Cortex in Alzheimer's Disease
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by prominent memory impairment, executive dysfunction, language, construction, and visuospatial deficits. In AD, the accumulation of neurofibrillary tangles neuritic plaques, and other associated neuropathology, results in widespread disruption of cortical connections. The entorhinal cortex (EC) is a region of cortical gray matter in the medial temporal lobe important in memory processing, and has been identified as the first structure affected in AD. The current study investigated the functional connectivity of the EC in AD and normal control (NC) subjects using functional connectivity magnetic resonance imaging (fcMRI). Additional goals of the study were to examine relationships between EC functional connectivity, EC volume, and neuropsychological measures of episodic memory and global cognitive ability. Nine NC and seven AD subjects were imaged using a 3.0 Tesla magnetic resonance scanner while resting quietly. Compared to the NC group, AD subjects exhibited significantly reduced functional connectivity with the EC in prefrontal cortex (BA 47, 10, 6, 9,&8), right superior temporal areas (BA 22&39), right fusiform gyrus (BA 37), and right perirhinal/entorhinal cortex (BA 35) extending into the hippocampus. Areas of significantly increased functional connectivity in AD subjects included bilateral inferior frontal gyrus (BA 47), left middle frontal gyrus (BA 46), left entorhinal/parahippocampal cortex (BA 28), and the left putamen. No significant relationships were detected among EC functional connectivity, EC volume, and cognitive measures. The findings of reduced EC connectivity in frontal and temporal association areas in AD are consistent with what is known about the progression of pathophysiology of AD, and provide support for the use of fcMRI in examining cortical connectivity patterns. Increased EC connectivity in prefrontal cortex may reflect the presence of compensatory mechanisms in the neural connections of AD patients. The lack of correlations among EC connectivity, EC volume, and neuropsychological measures suggests that more complex relationships among the variable may exist than was hypothesized. Future research investigating the relationships between functional integrity and structural volume, and how these variables relate to cognitive performance is needed.