Salience and frontoparietal network impairments across disease stages in dementia with Lewy bodies: A comparative functional MRI study with Alzheimer's disease

BackgroundResting-state functional magnetic resonance imaging (fMRI) studies in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have described connectivity alterations in large-scale brain networks. However, little is known about functional changes across disease stages, particularly in DLB.ObjectiveTo investigate functional connectivity of key brain networks in DLB patients at different stages, compare them to AD patients and healthy controls (HC), and examine associations with core clinical symptoms.MethodsNinety DLB patients (63 with mild cognitive impairment [MCI-DLB] and 27 with dementia [d-DLB]), 25 AD patients (11 MCI-AD and 14 d-AD) and 34 HC underwent clinical, neuropsychological and resting-state fMRI assessments. Region of interest (ROI)-to-ROI analyses were performed using the CONN toolbox (<i>p</i>_FDR < 0.05).ResultsThe overall DLB group showed reduced functional connectivity within the salience network (SN) compared to HC, but not to the overall AD group. At the subgroup level, d-DLB patients showed reduced SN and frontoparietal network (FPN) connectivity compared to both HC and the overall AD group, whereas MCI-DLB did not significantly differ from either group. In the overall DLB group, SN connectivity correlated with fluctuation severity and FPN connectivity correlated with both REM sleep behavior disorder and cognitive decline. In the overall AD group, decreased default mode network (DMN) connectivity was associated with lower Mini-Mental State Examination scores.ConclusionsSN and FPN connectivity impairments relate to disease progression and core clinical features in DLB, whereas DMN connectivity is linked to cognitive decline in AD. These distinct patterns highlight divergent paths of network dysfunction in the two diseases.<b>Clinical Trial:</b> This study is part of the AlphaLewyMA cohort, registered on ClinicalTrials.gov (identifier: NCT01876459; registered on June 12, 2013).