Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography

Objective The cause of the reduced regional cerebral blood flow (rCBF) in the posterior cingulate cortex in the early stage of Alzheimer's disease has not been clarified. In Alzheimer's disease, the posterior cingulate cortex itself shows little neuropathologic degeneration, and a hypothesis explaining such a discrepancy is that the functional impairment in the posterior cingulate cortex reflects remote effects caused by degeneration in distant but connected areas, such as the entorhinal cortex. To test the hypothesis, we investigated the functional connectivity between the entorhinal cortex and posterior cingulate cortex. posterior cingulate cortex, anterior cingulate cortex, lingual gyri and left middle temporal gyrus (P < 0.001), was observed in Alzheimer's disease. Control subjects also showed a similar correlation in the limbic and paralimbic systems, but not in the posterior cingulate cortex. Methods Sixty-one patients with probable Alzheimer's disease at a very early stage and 61 age-matched healthy controls underwent both brain structural magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Voxel-based morphometry was performed on MRI data to identify clusters of significantly reduced grey matter concentration in patients with Alzheimer's disease relative to controls, which were set as volumes of interest (VOIs) for correlation analyses of SPECT images. We then used adjusted rCBF values in the VOIs as covariates of interest in statistical parametric mapping. Results Voxel-based morphometry demonstrated a significant reduction in grey matter concentration in the bilateral entorhinal cortex in Alzheimer's disease. A positive correlation between rCBF in the entorhinal cortex as VOI and that in the limbic and paralimbic systems, including the posterior cingulate cortex, anterior cingulate cortex, lingual gyri and left middle temporal gyrus (P < 0.001), was observed in Alzheimer's disease. Control subjects also showed a similar correlation in the limbic and paralimbic systems, but not in the posterior cingulate cortex. Conclusion These results indicate that rCBF changes in the posterior cingulate cortex may be closely related to those in the entorhinal cortex in patients with Alzheimer's disease, thereby supporting the'remote effect' hypothesis.