A specific relationship between hippocampal CA1 subfield atrophy and episodic memory encoding in amnestic mild cognitive impairment

Abstract

uptake ratios were calculated within a ROI including frontal, temporoparietal, and retrosplenial cortices (FLR-ROI), using the cerebellum as reference region. Based on a FLR-threshold of 1.15, subjects were divided into PIBpositive (+) and -negative (-). Three age-matched groups were studied: A) 12 PIB(-) cognitively normal elderly controls, B) 12 PIB(+) cognitively normal elderly controls and C) 13 PIB(+) MCI-patients. Voxel-based and ROI-based statistical analyses were performed. The overlap between hypometabolism andWBC-abnormalities inMCI was used to define a ROI to extract values for correlation analysis between different modalities. Results: Group comparison between MCI and PIB(-) controls revealed significant hypometabolism and regionally overlapping WBC-reductions in MCI in posterior cingulate cortex/precuneus (typical cortical hubs, see figure 1). PIB-FLR values were negatively correlated with FDG-values (r 1⁄4 -0.67) and WBC-values (r 1⁄4 -0.42) and a linear positive correlation was found between FDG and WBC-values (r 1⁄4 0.51) across the entire population (groups A, B and C). These results survived correction for age and grey matter density.Conclusions: These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer-pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.