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Functional Interactions of the Entorhinal Cortex: An ¹⁸F-FDG PET Study on Normal Aging and Alzheimer’s Disease

¹ Department of Clinical Pathophysiology, Nuclear Medicine Unit, University of Florence, Italy
² Department of Neurological and Psychiatric Sciences, University of Florence, Italy
³ Neurological Clinic and Max-Planck-Institute for Neurological Research, University of Cologne, Germany

Alzheimer’s disease (AD) is a brain disorder characterized by reduced cerebral glucose metabolism (CMRgl) in several cortical regions. Evidence from neuropathology studies, animal models of AD, and ¹⁸F-FDG PET studies on cognitive impairment suggest that disrupted connections with the entorhinal cortex (EC) could be implicated in the emergence of the cortical hypometabolism. This ¹⁸F-FDG PET study assessed the functional interactions—that is, the intercorrelations between the EC and the whole brain in vivo—in normal aging and AD. Methods: Eighty-seven consecutive clinical AD patients underwent ¹⁸F-FDG PET scanning at rest. Thirty-five sex- and age-matched healthy elderly subjects were studied as controls (NC). A voxel-based correlation analysis was performed with statistical parametric mapping to assess significant correlations between relative CMRgl (rCMRgl) in the EC and the rest of the brain, for NC and AD patients. Results were considered significant at P < 0.001. Results: The pattern of EC functional interactions varies between normal aging and AD patients. In NC, the left and right EC were bilaterally correlated with several cortical and limbic regions, in accord with the major anatomic pathways identified in nonhuman primates. Alternatively, in AD patients, the EC correlations with the contralateral hemisphere were entirely lost, whereas those within the ipsilateral hemisphere were preserved only with the inferior temporooccipital (T–O) areas. Conclusion: This ¹⁸F-FDG PET correlation study indicates that AD-related processes lead to an altered functional relationship between the EC and several cortical and limbic regions, with respect to normal aging. Our results suggest that the assessment of coupled rCMRgl reductions between the EC and the ipsilateral T–O cortex, besides the typical pattern of cortical reduction, could increase ¹⁸F-FDG PET diagnostic sensitivity and further motivate its inclusion in the clinical assessment of AD.

Key Words: PET • ¹⁸F-FDG • Alzheimer’s disease • entorhinal cortex • functional interactions • connectivity • aging

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