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Default-mode network connectivity changes during the progression towards Alzheimer's dementia: A longitudinal functional MRI study.

BACKGROUND/PURPOSE
Brain function changes with Alzheimer's disease (AD) progression. Evaluating those changes longitudinally is important to understand the complex relationships between brain pathologies and cognition. We aimed (1) to identify longitudinal changes in functional connectivity in patients with mild cognitive impairment (MCI) characterized for amyloid-β (Aβ) status and (2) to relate these functional changes to clinical progression.


METHODS
Forty-four patients with MCI were followed using serial functional MRI over 1.2 years (three sessions) and cognitive testing over 3.1 years (five sessions). Intra and inter-network connectivities were computed to assess changes in brain connectivity using a network atlas adapted for late adulthood. Sixteen low Aβ clinically normal older adults underwent a single functional MRI session for group comparisons at baseline. Linear mixed-effects models with random intercept and slope were used to predict changes in connectivity based on Aβ status and progression to dementia.


RESULTS
At baseline, intra and inter-network resting-state fMRI connectivities did not differ by baseline clinical diagnosis, Aβ status, or clinical progression to dementia. At the final imaging session, progressive MCI had significantly higher connectivity compared to stable MCI, specifically within the default-mode network (DMN). Longitudinally, progressive MCI had increasing intra-DMN connectivity over time compared to stable MCI, and the rate of changes in connectivity was significantly associated with the rate of cognitive decline.


CONCLUSIONS
Intra-DMN connectivity increases in MCI patients progressing towards dementia, suggesting aberrant synchronization in the symptomatic stages of AD.