title: Connectivity Disruption, Atrophy, and Hypometabolism within Posterior Cingulate Networks in Alzheimer's Disease.
abstract: The posterior cingulate cortex (PCC) is a critical brain network hub particularly sensitive to Alzheimer's disease (AD) and can be subdivided into ventral (vPCC) and dorsal (dPCC) regions. The aim of the present study was to highlight functional connectivity (FC) disruption, atrophy, and hypometabolism within the ventral and dorsal PCC networks in patients with amnestic mild cognitive impairment (aMCI) or AD. Forty-three healthy elders (HE) (68.7 ± 6 years), 34 aMCI (73.4 ± 6.8 years) and 24 AD (70.9 ± 9.1 years) patients underwent resting-state functional MRI, anatomical T1-weighted MRI and FDG-PET scans. We compared FC maps obtained from the vPCC and dPCC seeds in HE to identify the ventral and dorsal PCC networks. We then compared patients and HE on FC, gray matter volume and metabolism within each network. In HE, the ventral PCC network involved the hippocampus and posterior occipitotemporal and temporoparietal regions, whereas the dorsal PCC network included mainly frontal, middle temporal and temporoparietal areas. aMCI patients had impaired ventral network FC in the bilateral hippocampus, but dorsal network FC was preserved. In AD, the ventral network FC disruption had spread to the left parahippocampal and angular regions, while the dorsal network FC was also affected in the right middle temporal cortex. The ventral network was atrophied in the bilateral hippocampus in aMCI patients, and in the vPCC and angular regions as well in AD patients. The dorsal network was only atrophied in AD patients, in the dPCC, bilateral supramarginal and temporal regions. By contrast, hypometabolism was already present in both the vPCC and dPCC networks in aMCI patients, and further extended to include the whole networks in AD patients. The vPCC and dPCC connectivity networks were differentially sensitive to AD. Atrophy and FC disruption were only present in the vPCC network in aMCI patients, and extended to the dPCC network in AD patients, suggesting that the pathology spreads from the vPCC to the dPCC networks. By contrast, hypometabolism seemed to follow a different route, as it was present in both networks since the aMCI stage, possibly reflecting not only local disruption but also distant synaptic dysfunction.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Mutlu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Landeau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Tomadesso
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Robin
authors.initials: R
authors.lastname: de Flores
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Mézenge
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, Service de NeurologieCaen, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: de La Sayette
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Eustache
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1077Caen, France; Université de Caen Normandie UMR-S1077Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077Caen, France; CHU de Caen, U1077Caen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
keywords: Alzheimer's disease; atrophy; hypometabolism; posterior cingulate cortex; resting-state functional connectivity