Distinct Changes in Functional Connectivity in Posteromedial Cortex Subregions during the Progress of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder which causes dementia, especially in the elderly. The posteromedial cortex (PMC), which consists of several subregions involved in distinct functions, is one of the critical regions associated with the progression and severity of AD. However, previous studies always ignored the heterogeneity of the PMC and focused on one stage of AD. Using resting-state functional magnetic resonance imaging, we studied the respective alterations of each subregion within the PMC along the progression of AD. Our data set consisted of 21 healthy controls, 18 patients with mild cognitive impairment (MCI), 17 patients with mild AD (mAD), and 18 patients with severe AD (sAD). We investigated the functional alterations of each subregion within the PMC in different stages of AD. We found that subregions within the PMC have differential vulnerability in AD. Disruptions in functional connectivity began in the transition area between the precuneus and the posterior cingulate cortex (PCC) and then extended to other subregions of the PMC. In addition, each of these subregions was associated with distinct alterations in the functional networks that we were able to relate to AD. Our research demonstrated functional changes within the PMC in the progression of AD and may elucidate potential biomarkers for clinical applications.

The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease

“…Moreover, these functional disruptions have been described in relation to an early and restricted involvement of the ventral PCC network, followed by subsequent cascades to the dorsal PCC at the AD dementia stage (Mutlu et al, ). However, we found the functional connectivity of the dorsal PCC was more prominently affected in AD, which is in accordance with a recent study showing that functional connectivity alterations originated in the dorsal PCC and later expanded to the ventral PCC region in severe AD cases (Wu et al, ). Recent work has also shown the dorsal PCC to be an integrative nexus of cortical connectivity responsible for modulating cognitive control processes (Leech et al, ).…”

“…It has been suggested that these abnormalities may underpin a precuneus‐hippocampal disconnection, and functional reductions in connected regions to the anterior cingulate (Sheline et al, ). Taken together, our findings concur with previous studies showing that different subregions of the PMC exhibit a differential vulnerability to AD (Petrella, Prince, Wang, Hellegers, & Doraiswamy, ; Wu et al, ; Xia et al, ).…”

“…Taken together, our findings concur with previous studies showing that different subregions of the PMC exhibit a differential vulnerability to AD (Petrella, Prince, Wang, Hellegers, & Doraiswamy, 2007;Wu et al, 2016;Xia et al, 2014).…”

“…A few resting‐state fMRI (rsfMRI) studies in AD have parcellated the PMC to examine its intrinsic functional architecture, however most have used a priori defined cortical seed regions to characterise its complex functional neuroanatomy (Cauda et al, ; Dillen et al, ; Margulies et al, ; Wu et al, ). Recent work has highlighted the advantages of connectivity‐based parcellation methods for a more detailed insight into the organisation of regional specialisation of brain regions (Eickhoff, Thirion, Varoquaux, & Bzdok, ; Thirion, Varoquaux, Dohmatob, & Poline, ).…”

Altered motion repulsion in Alzheimer’s disease

“…Comparing to healthy controls, AD patients show reduced activations in area V5 and parietal-occipital cortex in a previous functional magnetic resonance imaging study16. Recently, there is an emerging view that many neurological disorders including AD might be critically associated with altered cortical connectivity171819 and disrupted neural inhibition22021. However, the functional relevance of these impaired inhibitory processing on the perceptual dysfunctions in AD remains largely elusive.…”