Increased intra‐network functional connectivity in MCI patients progressing towards dementia compared to stable MCI

Abstract

AbstractBackgroundFew resting‐state functional magnetic resonance imaging (rs‐fMRI) studies were carried out in patients with mild cognitive impairment (MCI). Most were cross‐sectional and brought conflicting results with both decrease and increase of rs‐fMRI connectivity reported. We used a recently developed atlas of resting‐state networks specific for late adulthood to investigate longitudinal changes in rs‐fMRI in MCI patients, both within and between networks.MethodSixty older adults underwent rs‐fMRI using the Atlas55+[1] to assess intra and inter‐network functional connectivity and a baseline [18F]‐Flutemetamol‐PET to estimate their Amyloid‐β (Aβ) load. Sixteen stable Aβ‐negative clinically normal volunteers performed a baseline rs‐fMRI scan while 44 MCI patients performed 2 to 4 acquisitions with an average follow‐up duration of 14,5 months. Aβ was expressed in Centiloids and a threshold of 27 was used to define Aβ positivity based on previous work[2]. Intra and inter‐network functional connectivity analyses were performed using both progression to dementia and Aβ status as grouping variables. Demographics and follow‐up durations are provided in Table 1. Linear mixed‐models with random intercept and slope predicted changes in rs‐fMRI over time, adjusting for age, sex, education and e4 status.ResultWe observed that MCI patients who progressed to dementia during follow‐up had increased intra‐network connectivity over time, compared to stable MCI. Specifically, the time‐by‐outcome (progression vs stable) interaction for the intra‐network functional connectivity in the default‐mode, the executive control and the visual networks were significant (Fig. 1‐3). Similar results were found when limiting analyses to Aβ positive MCI and adjusting for volume effects, except for the visual network. Baseline intra‐network functional connectivity did not differ between groups (all p‐values>0,05). Inter‐network functional connectivity did not change between groups over time (all p>0,05).ConclusionIn Alzheimer's Disease, intra‐network functional connectivity increases during the progression of MCI to dementia compared to stable MCI.