A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease

J Alzheimers Dis. 2017;55(2):521-537. doi: 10.3233/JAD-150695.


Background/objective: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy.

Methods: We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups.

Results: At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls.

Conclusion: We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

Keywords: Alzheimer’s disease; frontotemporal dementia; frontotemporal lobar degeneration; functional connectivity; longitudinal; resting state fMRI; resting state networks.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / physiopathology*
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Brain Mapping
  • Female
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / physiopathology*
  • Gray Matter / diagnostic imaging
  • Humans
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology*
  • Oxygen / blood
  • Rest*
  • White Matter / diagnostic imaging


  • Oxygen