Brain network connectivity differs in early-onset neurodegenerative dementia

OBJECTIVE To investigate functional brain network architecture in early-onset Alzheimer disease (EOAD) and behavioral variant frontotemporal dementia (bvFTD). METHODS Thirty-eight patients with bvFTD, 37 patients with EOAD, and 32 age-matched healthy controls underwent 3D T1-weighted and resting-state fMRI. Graph analysis and connectomics assessed global and local functional topologic network properties, regional functional connectivity, and intrahemispheric and interhemispheric between-lobe connectivity. RESULTS Despite similarly extensive cognitive impairment relative to controls, patients with EOAD showed severe global functional network alterations (lower mean nodal strength, local efficiency, clustering coefficient, and longer path length), while patients with bvFTD showed relatively preserved global functional brain architecture. Patients with bvFTD demonstrated reduced nodal strength in the frontoinsular lobe and a relatively focal altered functional connectivity of frontoinsular and temporal regions. Functional connectivity breakdown in the posterior brain nodes, particularly in the parietal lobe, differentiated patients with EOAD from those with bvFTD. While EOAD was associated with widespread loss of both intrahemispheric and interhemispheric functional correlations, bvFTD showed a preferential disruption of the intrahemispheric connectivity. CONCLUSIONS Disease-specific patterns of functional network topology and connectivity alterations were observed in patients with EOAD and bvFTD. Graph analysis and connectomics may aid clinical diagnosis and help elucidate pathophysiologic differences between neurodegenerative dementias.