Olfactory tract dysintegrity and cortical metabolic change in aging and MCI

Abstract

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Objectives: Olfactory dysfunction is an early feature of Alzheimer’s disease (AD). We hypothesized that mild cognitive impairment (MCI) would show olfactory tract (OT) dysintegrity through diffusion tensor imaging (DTI) and correlate to neuronal dysfunction seen in the central olfactory system on PET.

Methods: MCI (n=7, 75.2±6.5 yrs.) and normals (age-matched subset: n=8, 75.3±7.5 yrs. and all: n=25, 48 – 88 yrs) had standard brain FDG-PET and DTI with 32 gradients on a 3T MRI. Fractional anisotropy (FA) maps were generated (DTIstudio). PET and FA images in each subject were coregistered and mapped stereotactically (NEUROSTAT). Individual MCI PET images were compared to a normal database to verify typical ‘AD pattern’ hypometabolism. VOI analysis of FA and FDG images was performed. Voxel-wise correlation between OT FA values and metabolic activities was performed over the entire brain.

Results: Five MCI showed metabolic patterns of AD. These subjects showed OT degeneration (FA_MCI=0.29±0.4 and FA_NORM=0.22±0.04, p≤0.01) and metabolic reduction (p≤0.05) in posterior (PC) and anterior cingulate (AC), Parieto-temporal (PT), and parahippocampal gyri and amygdala (AMG). OT degeneration in normal aging was associated with fronto-temporal metabolic alteration, which became more robust with MCI included (med. frontal z=4.8, hippocampus/AMG z=4.2, AC z=4.2 and insula/med. temporal z=3.9). MCI, but not normals showed additional correlated metabolic changes in areas typically involved in AD (PC z=4.5 and PT z=4.4).

Conclusions: Olfactory tract degeneration correlated with metabolic changes in the central olfactory system and progressive changes associated with probable AD processes in MCI, indicate co-existing olfactory tract pathophysiology in aging and AD.

Research Support: RO1NS045254