Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations.

David López-Sanz,Ricardo Bruña,Ramón López Higes,Pilar Garcés,Alberto Marcos,María Carmen Martín-Buro,Stefan Walter,Fernando Maestú,Mercedes Montenegro,María Luisa Delgado

doi:10.3389/fnagi.2017.00109

Abstract

Functional connectivity (FC) alterations represent a key feature in Alzheimer's Disease (AD) and provide a useful tool to characterize and predict the course of the disease. Those alterations have been also described in Mild Cognitive Impairment (MCI), a prodromal stage of AD. There is a growing interest in detecting AD pathology in the brain in the very early stages of the disorder. Subjective Cognitive Decline (SCD) could represent a preclinical asymptomatic stage of AD but very little is known about this population. In the present work we assessed whether FC disruptions are already present in this stage, and if they share any spatial distribution properties with MCI alterations (a condition known to be highly related to AD). To this end, we measured electromagnetic spontaneous activity with MEG in 39 healthy control elders, 41 elders with SCD and 51 MCI patients. The results showed FC alterations in both SCD and MCI compared to the healthy control group. Interestingly, both groups exhibited a very similar spatial pattern of altered links: a hyper-synchronized anterior network and a posterior network characterized by a decrease in FC. This decrease was more pronounced in the MCI group. These results highlight that elders with SCD present FC alterations. More importantly, those disruptions affected AD typically related areas and showed great overlap with the alterations exhibited by MCI patients. These results support the consideration of SCD as a preclinical stage of AD and may indicate that FC alterations appear very early in the course of the disease.

Highlights

The increase in life expectancy during the last decades has an inherent downside: the increase of dementia cases in the population (Brookmeyer et al, 2007)
When observed in the pairwise comparison, the results showed a posterior network, with decreased connectivity, and an anterior network, with increased connectivity for both Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) compared to the HC group
We have showed that elders presenting with SCD, in spite of their normal neuropsychological performance, exhibit a pattern of Functional connectivity (FC) alterations similar to that shown by MCI patients

Summary

Introduction

The increase in life expectancy during the last decades has an inherent downside: the increase of dementia cases in the population (Brookmeyer et al, 2007). The description of Mild Cognitive Impairment (MCI), an intermediate state between healthy individuals and dementia patients, represented an important step toward the early diagnose of AD. MCI is characterized by slight cognitive impairment in one or more domains and increased risk of developing dementia (Petersen, 2004). SCD could represent a prodromal stage of MCI in which individuals report a worsening in their cognitive skills that current neuropsychological assessment tools are not able to capture. SCD subjects are at a greater risk for developing MCI or AD compared to healthy elders (Jessen et al, 2010, 2014; Reisberg et al, 2010; Mitchell et al, 2014). Whilst there are still inconsistent results, some neuroimaging studies reported ADrelated brain pathology in SCD supporting its interpretation as an asymptomatic stage of AD as reviewed by Sun et al (2015)

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Conclusion