SPECT imaging of GABA sub(A)/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment

Purpose: The involvement of neocortical and limbic GABA sub(A)/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 GABA sub(A)/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. Methods: [ super(123)I]Iomazenil and [ super(99m)Tc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [ super(123)I]iomazenil imaging in 5, only [ super(99m)Tc]HMPAO imaging in 4, and both [ super(123)I]iomazenil and [ super(99m)Tc]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 [ super(123)I]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 2years 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 GABA sub(A)/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [ super(99m)Tc]HMPAO rCBF imaging is more sensitive than [ super(123)I]iomazenil GABA sub(A)/BZD receptor imaging in detecting prodromal AD.