Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of progression to dementia

Abstract

[(18)F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild Cognitive Impairment (MCI), supporting the presence or the exclusion of Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies MCI definition. In this study, we aimed to evaluate the predictive role of single-subject voxel-based maps of [(18)F]FDG distribution generated through statistical parametric mapping (SPM) in the progression to different dementia subtypes in a sample of 45 MCI. Their scans were compared to a large normal reference dataset developed and validated for comparison at single-subject level. Additionally, Aβ42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up (mean 28.5 ± 7.8 months) assessed subsequent progression to AD or non-AD dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases, none of them progressing to dementia; 2) the typical temporo-parietal pattern suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in 7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral or bilateral temporo-medial hypometabolism without the typical AD pattern, and they all remained stable. In our sample, objective voxel-based analysis of [(18)F]FDG-PET scans showed high predictive prognostic value, by identifying either normal brain metabolism or hypometabolic patterns suggestive of different underlying pathologies, as confirmed by progression at follow-up. These data support the potential usefulness of this SPM [(18)F]FDG PET analysis in the early dementia diagnosis and for improving subject selection in clinical trials based on MCI definition.

Keywords: Alzheimer's disease; Dementia diagnosis; Mild Cognitive Impairment; PET imaging; [18F]FDG.

Fig. 1

The SPM-t maps of hypometabolism of eight MCI cases, as example: PET patterns corresponding to Alzheimer's disease (A, B), behavioral variant of frontotemporal dementia (C, D), semantic variant of primary progressive aphasia (E), corticobasal degeneration (F), dementia with Lewy bodies (G, H). Yellow/red scales shown in SPM maps are regions which are hypometabolic in MCI patient in comparison to the normal control database (see text for details).

Fig. 2

The SPM-t map of hypometabolism of an amnestic single domain MCI with mTLD-pattern displayed on axial view of an MRI standardized structural scan showing a selective temporo-mesial hypometabolic pattern (A). Axial T1-weighted MRI images showing mild-moderate selective temporo-mesial atrophy more pronounced on the left side (B). L = left; R = right.