Relatively Reduced Default Mode Network Connectivity in Comparison to The Severity of White Matter Involvement is Associated With Severe Memory Deficits and Poor Cognitive Outcomes in Patients With Idiopathic Normal Pressure Hydrocephalus.

Abstract

Background: The aim of this study was to investigate whether default mode network (DMN) connectivity and brain white matter integrity at baseline were associated with severe cognitive impairments at baseline and poor cognitive outcomes after shunt placement in patients with idiopathic normal pressure hydrocephalus (iNPH).Methods: Twenty consecutive patients with iNPH whose symptoms were followed for 6 months after shunt placement and 10 healthy controls (HCs) were enrolled. DMN connectivity and brain white matter integrity in patients with iNPH at baseline were detected by performing resting-state functional magnetic resonance imaging with independent component analysis and by using diffusion weighted imaging with tract-based spatial statistics, respectively. Performance on the neuropsychological tests for memory and executive functions and gait test was assessed in patients with iNPH at baseline and 6 months after shunt placement.Results: The mean DMN connectivity in the iNPH group was significantly reduced compared with that in the HC group and was significantly positively correlated with the scores of the Rey auditory verbal learning test (RAVLT) immediate recall and the frontal assessment battery (FAB). The mean fractional anisotropy of the whole-brain white matter skeleton in the iNPH group was significantly lower than that in the HC group. We divided the patients with iNPH into relatively preserved and reduced DMN connectivity groups using the indexes of DMN connectivity and white matter integrity. The reduced DMN connectivity group showed significantly worse performance on RAVLT at baseline and significantly worse improvement of RAVLT immediate recall and FAB scores compared with the preserved DMN connectivity group. Moreover, the RAVLT immediate score/the FAB score ratio highly distinguished the patients with relatively preserved DMN connectivity from those with relatively reduced DMN connectivity.Conclusions: Our findings indicated that iNPH patients with relatively reduced DMN connectivity in comparison to the severity of brain white matter involvement are associated with severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. In addition, DMN connectivity/brain white matter integrity and RAVLT immediate score/FAB score ratios are useful predictors of poor cognitive outcomes after shunt placement.