Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease

Background: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (A beta), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. Methods: Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral A beta was measured by C-11 Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-epsilon 4 carrier status). Results: A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-epsilon 4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022). Conclusion: Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.