Consistent inter-protocol differences in resting-state functional connectomes between normal aging and mild cognitive impairment

Abstract

Resting-state functional connectivity is a promising biomarker for Alzheimers disease. However, previous resting-state functional magnetic resonance imaging studies in Alzheimers disease and mild cognitive impairment (MCI) have shown limited reproducibility as they have had small sample sizes and substantial variation in study protocol. We sought to identify functional brain networks and connections that could consistently discriminate normal aging from MCI despite variations in scanner manufacturer, imaging protocol, and diagnostic procedure. We therefore pooled four independent datasets, including 112 healthy controls and 143 patients with MCI, systematically testing multiple brain connections for consistent differences. The largest effects associated with MCI involved the ventromedial and dorsomedial prefrontal cortex, striatum, and middle temporal lobe. Compared with controls, patients with MCI exhibited significantly decreased connectivity within the frontal lobe, between frontal and temporal areas, and between regions of the cortico-striatal-thalamic loop. Despite the heterogeneity of methods among the four datasets, we identified robust MCI-related connectivity changes that appear to be promising candidate biomarkers for Alzheimers disease.