Advertisement

LONGITUDINAL INTRINSIC FUNCTIONAL CONNECTIVITY CHANGES IN PRECLINICAL ALZHEIMER’S DISEASE: A TWO-YEAR FOLLOW UP STUDY

      Background

      Although previous cross sectional studies demonstrated intrinsic functional connectivity (FC) changes in the preclinical Alzheimer’s disease (AD), effects of amyloid burden in FC changes are still not yet clear on the longitudinal basis

      Methods

      Sixty four florbetaben (FBB) amyloid PET defined NIA-AA preclinical AD subjects (stage 1 (N= 31) and stage2/3 (N=33)) and 32 healthy control subjects (stage 0) completed resting state functional magnetic resonance imaging (fMRI) scans. FC changes were examined for three networks of interest (default mode network (DMN), salience network (SN), and central executive network (CEN)) using independent component analysis during a 2-year follow-up. We also analyzed the group by amyloid retention with FC changes in the three networks.

      Results

      Longitudinal analysis showed that the DMN of the stage 1 subjects showed significantly increased FC compared to the stage 0 and 2/3 subjects. On the other hand, stage 2/3 subjects showed decreased FC compared to stage 0 and 1 subjects. The FC of the CEN showed significantly decreased in the stage 1 and increased in stage 2/3 during the follow up periods. There were no longitudinal FC changes in SN in all subjects. In addition, there were significant group x FBB amyloid retention level interaction with FC changes in the posterior DMN.

      Conclusions

      Our results of aberrant DMN FC changes and distinctive interaction patterns might reflect a biphasic trajectory of changes in FC in preclinical AD subjects. These changes might have clinical implications as surrogate markers of efficacy in clinical trials of the disease modifying agents.