Abstract

ObjectiveTo assess the contribution of regional grey matter (GM) atrophy and functional disconnection in determining the level of cognitive decline in patients with Alzheimer's disease (AD) at different clinical stages.MethodsTen...

Highlights

  • The clinical presentation of Alzheimer’s disease (AD) is typically characterized by an early and prominent impairment of memory functions, followed by a progressive accumulation of additional cognitive deficits, eventually resulting in dementia[1]

  • This study indicates that disconnection precedes grey matter (GM) atrophy in the posterior cingulate cortex (PCC), which is a critical area of the default mode network (DMN), and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflect a long-term effect of brain disconnection

  • The current study combines functional and structural MRI to quantify the relative role played by regional GM atrophy over the transitional stage between normal aging and dementia, by considering amnesic mild cognitive impairment (a-mild cognitive impairment (MCI)) as an early clinical stage of AD

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Summary

Introduction

The clinical presentation of Alzheimer’s disease (AD) is typically characterized by an early and prominent impairment of memory functions, followed by a progressive accumulation of additional cognitive deficits, eventually resulting in dementia[1]. The so-called default-mode network (DMN), which includes the PCC, inferior parietal, and medial prefrontal cortex (mPFC) has been identified as a neuronal network showing a coherent pattern of activation (functional connectivity)[11] These regions, which show correlation in their spontaneous fluctuations at rest, are believed to be modulated by cognitive tasks. Voxel-based morphometry (VBM) is a spatially-specific and unbiased method of analysis of MR images reflecting the regional GM volume at a voxel scale[12] This technique has already been successfully applied to AD, showing patterns of GM abnormalities that fit well with the clinical stage of the disease, and predict the risk of conversion from mild cognitive impairment (MCI)[13], which is a condition associated with an high risk of conversion to AD in short time, to AD14 15

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