Hippocampal Resting-State Functional Connectivity Patterns are More Closely Associated with Severity of Subjective Memory Decline than Whole Hippocampal and Subfield Volumes.

Lauren Zajac,Jesse Mez,Bang-Bon Koo,Ronald Killiany,Asim Mian,Yorghos Tripodis,Eric Steinberg,Anna Cervantes-Arslanian,Michael L Alosco,Robert Stern

doi:10.1093/texcom/tgaa019

Abstract

The goal of this study was to examine whether hippocampal volume or resting-state functional connectivity (rsFC) patterns are associated with subjective memory decline (SMD) in cognitively normal aged adults. Magnetic resonance imaging data from 53 participants (mean age: 71.9 years) of the Boston University Alzheimer’s Disease Center registry were used in this cross-sectional study. Separate analyses treating SMD as a binary and continuous variable were performed. Subfield volumes were generated using FreeSurfer v6.0, and rsFC strength between the head and body of the hippocampus and the rest of the brain was calculated. Decreased left whole hippocampal volume and weaker rsFC strength between the right body of the hippocampus and the default mode network (DMN) were found in SMD+. Cognitive Change Index score was not correlated with volumetric measures but was inversely correlated with rsFC strength between the right body of the hippocampus and 6 brain networks, including the DMN, task control, and attentional networks. These findings suggest that hippocampal rsFC patterns reflect the current state of SMD in cognitively normal adults and may reflect subtle memory changes that standard neuropsychological tests are unable to capture.

Highlights

It is important to reliably identify individuals with significant risk of developing dementia in the cognitively normal population in order to test the efficacy of interventions to stop or slow progression before substantial, irreversible neurodegeneration takes place (Sperling et al 2011a, 2011b)
The goal of this study was to examine whether hippocampal volume or resting-state functional connectivity patterns are associated with subjective memory decline (SMD) in cognitively normal aged adults
Similar to the results presented in section Hippocampal resting-state functional connectivity (rsFC) Strength Between-Group Analyses, the number of inverse correlations between Cognitive Change Index (CCI) score and rsFC strength involving the right body of the hippocampus relative to the number of inverse correlations involving the other 3 hippocampal regions combined was significantly greater than chance (P = 0.0007)

Summary

Introduction

It is important to reliably identify individuals with significant risk of developing dementia in the cognitively normal population in order to test the efficacy of interventions to stop or slow progression before substantial, irreversible neurodegeneration takes place (Sperling et al 2011a, 2011b). Some rsFC studies have found stronger rsFC in those reporting SMD (Hafkemeijer et al 2013; Kawagoe et al 2019), whereas others have found weaker rsFC in those reporting SMD (Wang et al 2013; Yasuno et al 2015; Viviano et al 2019) Some of these studies have focused on the default mode network (DMN), which is heavily associated with memory function and self-referential processing and affected in aging and AD (see Buckner et al 2005 for review; Andrews-Hanna et al 2007, 2010; Jones et al 2011, 2015). These aspects of MRI may eventually help pinpoint more reliable imaging biomarkers for differentiating between those in the cognitively normal population who express features in the brain that are early signs of dementia from those who express features solely related to factors such as mood and medication, both of which can impact memory

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