Differences of neural interactions between early and late onset Alzheimer’s disease: A network analysis

Abstract

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Objectives: Early-onset (EO) and late-onset (LO) Alzheimer’s diseases (ADs) are known to have different cognitive decline profiles and pathophysiology. The present study was designed to determine and compare the neural interactions underlying general cognitive function for the two subtypes of Alzheimer’s disease using FDG PET and path analysis.

Methods: FDG PET imaging was performed in 73 patients with EO AD (AD onset before 65 yr) (age 59.1± 5.7 y, 49 females/24 males, MMSE score 17.5±6.9), 47 patients with late onset AD (age 74.1±4.7 y, 33 females /14 males, MMSE 18.9±6.5) and 15 young (54.0±2.8 y, 6/9) and 20 aged (69.0±4.1 y, 12/8) healthy controls. For path analysis, five brain regions (middle and inferior frontal, inferior temporal gyri, inferior parietal lobule, and posterior cingulate) were selected in each hemisphere based on the results of the correlation analysis between MMSE score and regional brain glucose metabolism using SPM99. Hippocampus was selected additionally because this area is important for the pathology of AD. Voxel values for each coordinate were extracted from the data set of each subject. For the model construction, anatomical connection was defined based on the previous researches. First, we tested the goodness-of-fit to assess the suitability of the constructed model. Second, using this model, we evaluated the differences in the path model between two patients groups. All the model construction and path analysis processing was done by AMOS 5.0 (SmallWaters Co.)

Results: Goodness-of-fit of final constructed model was selected [X2 (4) =3.12, P=0.54 in left and X2 (4) = 1.88, P=0.76 in right]. In both hemispheres, the intra-hemispheric functional networks proved to be significantly different between the two AD groups [left: X2 diff (13) = 28.38, P < 0.01; right: X2 diff (13) = 27.65, P < 0.05]. Comparing with functional network of age-matched normal controls, several inter-regional connections were weakened in both AD group. In EO AD, especially the neural connections from frontal to lateral and medial temporal area were changed while in LO AD, those of frontal to posterior cingulate and hippocampus to posterior cingulate were changed.

Conclusions: Our data demonstrate the different patterns of dysorganization in functional network between EO and LO AD patients. They provide additional insight into the pathophysiology of AD subtypes and neural functioning for cognitive processes.