SPECT imaging of GABAA/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment

Sabina Pappatà, Andrea Varrone, Caterina Vicidomini, Graziella Milan, Caterina De Falco, Valeria Sansone, Alessandro Iavarone, Marco Comerci, Elisa Loré, Maria Rosaria Panico, Mario Quarantelli, Alfredo Postiglione, Marco Salvatore

Research output: Contribution to journalArticle

Abstract

Purpose The involvement of neocortical and limbic GABAA/ benzodiazepine (BZD) receptors in Alzheimer's disease (AD) is controversial and mainly reported in advanced stages. The status of these receptors in the very early stages of AD is unclear and has not been explored in vivo. Our aims were to investigate in vivo the integrity of cerebral cortical GABAA/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. Methods [123I] Iomazenil and [99mTc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [ 123I] iomazenil imaging in 5, only [99mTc]HMPAO imaging in 4, and both [123I]iomazenil and [99mTc]HMPAO imaging in 5). Region of interest (ROI) analysis and voxel-based analysis were performed with cerebellar normalization. Results Neither ROI analysis nor voxel-based analysis showed significant [123I]iomazenil binding changes in MCI patients compared to control subjects, either as a whole group or when considering only those patients with MCI that converted to AD within 2 years of clinical follow-up. In contrast, the ROI analysis revealed significant hypoperfusion of the precuneus and posterior cingulate cortex in the whole group of MCI patients and in MCI converters as compared to control subjects. Voxel-based analysis showed similar results. Conclusion These results indicate that in the very early stages of AD, neocortical and limbic neurons/synapses expressing GABAA/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [99mTc]HMPAO rCBF imaging is more sensitive than [123I]iomazenil GABAA/BZD receptor imaging in detecting prodromal AD.

Original languageEnglish
Pages (from-to)1156-1163
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume37
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Alzheimer
  • Benzodiazepine receptors
  • Cerebral perfusion
  • Iomazenil
  • Mild cognitive impairment
  • SPECT

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Pappatà, S., Varrone, A., Vicidomini, C., Milan, G., De Falco, C., Sansone, V., Iavarone, A., Comerci, M., Loré, E., Panico, M. R., Quarantelli, M., Postiglione, A., & Salvatore, M. (2010). SPECT imaging of GABAA/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment. European Journal of Nuclear Medicine and Molecular Imaging, 37(6), 1156-1163. https://doi.org/10.1007/s00259-010-1409-1