Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks

Alzheimer’s disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge to the hippocampus in the healthy brain. As neurodegeneration is thought to spread within preexisting networks, the common hippocampal atrophy in both diseases is likely due to its location at the crossroad between both vulnerable networks. Yet, we showed that in the normal brain, these networks harbor different functions, with episodic memory relying on the AD-vulnerable network only. Overall, disease-associated cognitive deficits seem to reflect the disruption of targeted networks more than atrophy in specific brain regions: in AD, over hippocampal atrophy, episodic memory deficits are likely due to disconnection within a memory-related network. •Hippocampal atrophy is severe in both Alzheimer’s disease and semantic dementia•In the normal brain, the hippocampus is connected to AD and SD vulnerable regions•Hippocampal connectivity is related to episodic memory only within the AD network•This network specificity likely explains the sparing of episodic memory in SD Hippocampal atrophy is associated with severe episodic memory deficits in Alzheimer’s disease but not semantic dementia. La Joie et al. relate this paradox to the differential impairment of partly overlapping but functionally different large-scale networks that both involve the hippocampus.