Delusions in Alzheimer Disease are Associated With Decreased Default Mode Network Functional Connectivity

Objective: Approximately one-third of patients with Alzheimer disease (AD) develop delusions. Delusions have been linked to numerous adverse outcomes, including worsened cognitive and functional decline, increased caregiver burden, and higher mortality rates. Previous studies have indicated that both AD and neuropsychiatric symptoms within AD are associated with abnormal functional connectivity of the resting brain, but no studies have focused on how delusions alter resting-state functional connectivity. The authors' objective was to test for differences in resting brain function between delusional and non-delusional patients with AD. The authors hypothesized that patients with AD with delusions would exhibit reduced connectivity of the default mode network (DMN) compared with patients with AD without delusions. Methods: Resting-state functional magnetic resonance imaging was used to investigate differences in functional connectivity between 15 patients with AD with delusions and 15 comparable patients with AD without delusions. A group-level principal component analysis was used to identify functional networks accounting for greatest variability over all subjects, and the DMN was selected for between-group analysis. Dual regression was used to reconstruct individual subject component maps, and a two-sample t test was used to compare groups with and without delusion, adjusted at a false discovery rate of 0.05. Results: The two cohorts were comparable demographically and cognitively. The patients with delusions showed significantly reduced connectivity of the left inferior parietal lobule (IPL) with the rest of the DMN. Conclusion: Delusions in AD are associated with reduced connectivity within the DMN, specifically the left IPL. The authors' findings provide insight into the underlying neuropathophysiology of delusions in AD.