Connectivity Disruption, Atrophy, and Hypometabolism within Posterior Cingulate Networks in Alzheimer's Disease.

Justine Mutlu,Florence Mézenge,Brigitte Landeau,Gaël Chételat,Clémence Tomadesso,Francis Eustache,Vincent De La Sayette,Robin De Flores

doi:10.3389/fnins.2016.00582

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.

Highlights

Alzheimer’s disease (AD) is the most widespread cause of dementia
Atrophy Within the vPCC network, significant atrophy was found in the bilateral hippocampus and parahippocampal gyrus in patients with amnestic mild cognitive impairment (aMCI) compared with healthy elders (HE)
In patients with AD, the vPCC network was atrophied in the bilateral hippocampus, parahippocampal and fusiform gyri, bilateral vPCC, cuneus and posterior part of the precuneus, FIGURE 4 | Brain areas showing significant functional connectivity (FC) disruptions (A), atrophy (B), and hypometabolism (C) within the ventral and dorsal posterior cingulate cortex (PCC) networks of patients with aMCI or AD compared with HE, as revealed by ANCOVAs thresholded at p

Summary

Introduction

Alzheimer’s disease (AD) is the most widespread cause of dementia. This neurodegenerative disease is characterized by a progressive decline in cognitive performances, typically predominated by episodic memory deficits. In vivo neuroimaging biomarkers of the disease include atrophy (predominantly in the hippocampus and temporal neocortex), hypometabolism (mainly in the posterior cingulate cortex (PCC), and temporo-parietal cortex), and amyloid deposition in medial frontal and parietal and temporo-parietal cortical areas (McKhann et al, 2011; Winblad et al, 2016). Recent neuroimaging studies have shown that the topography of atrophy/hypometabolism in AD (and other forms of dementia) follows specific brain connectivity networks, as evidenced by resting-state functional magnetic resonance imaging (fMRI), for instance, leading to the network degeneration hypothesis (Seeley et al, 2009; La Joie et al, 2014). The default mode network (DMN) includes those brain areas that are most sensitive to AD (i.e., sites of the earliest atrophy, hypometabolism and/or amyloid deposition), such as the PCC, precuneus, hippocampus, temporo-parietal, and medial frontal areas (Greicius et al, 2004; Sheline and Raichle, 2013)

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