Longitudinal robustness of resting‐state functional connectivity signatures across different stages of the Alzheimer’s disease continuum

Abstract

AbstractBackgroundA growing number of resting‐state fMRI (rs‐fMRI) studies report changes in network activity to be a frequent and often early pathological feature in many neurodegenerative conditions. The majority of studies have primarily focused on changes in group averages, failing to account for individual functional connectivity (FC) idiosyncrasies that have been shown to provide a unique identifier or “fingerprint” in healthy individuals (Finn et al., 2015). It thus remains unclear to what extent FC‐signatures are stable in the context of cognitive decline and Alzheimer’s Disease (AD) pathology (e.g., β‐amyloid [Aβ] and tau). We studied the robustness of subject‐specific FC in a longitudinal cohort covering the AD spectrum.Method275 participants with longitudinal rs‐fMRI data—baseline plus a follow up after approximately two‐years—were selected from the Swedish BioFINDER‐2 cohort, split into six groups: cognitively normal (CN) Aβ‐, subjective cognitive decline (SCD) Aβ‐, SCD Aβ+, mild cognitive decline (MCI) Aβ‐, MCI Aβ+, and AD Aβ+. FC matrices were derived from each subject rs‐fMRI session using the Schaefer cortical parcellation (200 and 400 ROIs), and consequently, a 275×275 identifiability matrix (IM) was derived; see Fig. 1B. For each subject, two fingerprinting measures were extracted from the IM: self identifiability (I‐self) and differential identifiability (I‐diff); see Fig.1B.ResultI‐self and I‐diff show varied distributions across the six groups, but values remain notably high even within the AD Aβ+ (Fig.2A). Both I‐self and I‐diff show significant differences between CN Aβ‐ and AD Aβ+ (Fig.2B). SCD Aβ‐ not only show a greater difference to AD Aβ+, but also to SCD Aβ+ and MCI Aβ+; see Fig.2B. Baseline tau‐PET was associated with I‐self (r = ‐0.1928,p = 0.0014) and to a lesser degree with I‐diff (r = ‐0.1293, p = 0.0334), whereas baseline MMSE was only found associated to I‐self (r = 0.1671,p = 0.0055); neither I‐self nor I‐diff were associated with age (Fig.3).ConclusionOur results suggest that resting‐state FC is mostly stable under cognitive decline and presence of AD pathology. FC was most notably differentiable for SCD Aβ‐, suggesting it as a potential signature to decipher underlying cognitive status and to predict likelihood of future conversion to AD.