Altered anterior cingulate cortex subregional connectivity associated with cognitions for distinguishing the spectrum of pre-clinical Alzheimer’s disease

Abstract

BackgroundSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered part of the early progression continuum of Alzheimer’s disease (AD). The anterior cingulate cortex (ACC), a hub of information processing and regulation in the brain, plays an essential role in AD pathophysiology. In the present study, we aimed to systematically identify changes in the functional connectivity (FC) of ACC subregions in patients with SCD and aMCI and evaluate the association of these changes with cognition.Materials and methodsFunctional connectivity (FC) analysis of ACC sub-regions was performed among 66 patients with SCD, 71 patients with aMCI, and 78 healthy controls (HCs). Correlation analyses were performed to examine the relationship between FC of altered ACC subnetworks and cognition.ResultsCompared to HCs, SCD patients showed increased FC of the bilateral precuneus (PCUN) and caudal ACC, left superior frontal gyrus (SFG) and subgenual ACC, left inferior parietal lobule (IPL) and dorsal ACC, left middle occipital gyrus (MOG) and dorsal ACC, and left middle temporal gyrus (MTG) and subgenual ACC, while aMCI patients showed increased FC of the left inferior frontal gyrus (IFG) and dorsal ACC and left medial frontal gyrus (MFG) and subgenual ACC. Compared to patients with SCD, patients with aMCI showed increased FC of the right MFG and dorsal ACC and left ACC and subgenual ACC, while the left posterior cingulate cortex (PCC) showed decreased FC with the caudal ACC. Moreover, some FC values among the altered ACC subnetworks were significantly correlated with episodic memory and executive function.ConclusionSCD and aMCI, part of the spectrum of pre-clinical AD, share some convergent and divergent altered intrinsic connectivity of ACC subregions. These results may serve as neuroimaging biomarkers of the preclinical phase of AD and provide new insights into the design of preclinical interventions.

Identifying discriminative features of brain network for prediction of Alzheimer’s disease using graph theory and machine learning

“…It has also been observed that early symptoms of AD appear as atrophy in the ACC, which is also an important component of the DMN (Xu et al, 2016;Chen et al, 2021;Tu et al, 2021). This atrophy has been frequently observed as an early symptom in clinical investigations (Lee et al, 2020;Yuan et al, 2022). Hence, we specifically examined ACC and rest of the cingulate cortex (PCC and MCC) with top13ROI.…”

“…In addition, altered (increased or decreased) FC patterns have been reported in anterior and posterior cingulate cortex (ACC and PCC) regions. It is argued that this could also serve as biomarker ( Dickerson and Sperling, 2008 ; Yuan et al, 2022 ). These findings support the potential of fMRI as a predictive tool for AD in its early stages.…”

Accelerated long-term forgetting: A sensitive paradigm for detecting subtle cognitive impairment and evaluating BACE1 inhibitor efficacy in preclinical Alzheimer's disease

“…Given that SCD assessment may be affected by many artifact factors including the way of quantifying cognitive complaints, recruitment settings and the threshold used for cognitive normality, ALF provides a more powerful preclinical cognitive measure that can detect objectively subtle changes at the earliest stage of AD continuum. It is tempting to speculate that ALF detectable in SCD individuals before diagnosis may be associated with altered functional connectivity in prefrontal cortical areas including the ACC (Yuan et al, 2022 ), which shows highest regional Aβ load associated with local atrophy by PET imaging (Chételat et al, 2010 ). The findings support the concept that changes in different brain structures may underlie two distinct forms of amnesia, classical hippocampal amnesia (MCI and thereafter) and ALF at an earlier preclinical stage reflecting impaired cortical long-term memory consolidation.…”