Abstract
We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB.Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Dynamic connectivity measures that showed significant group differences were tested for correlations with clinical symptom severity.Our results show that AD and DLB patients spent more time than controls in sparse connectivity configurations with absence of strong positive and negative connections and a relative isolation of motor networks from other networks. Additionally, DLB patients spent less time in a more strongly connected state and the variability of global brain network efficiency was reduced in DLB compared to controls. There were no significant correlations between dynamic connectivity measures and clinical symptom severity.An inability to switch out of states of low inter-network connectivity into more highly and specifically connected network configurations might be related to the presence of dementia in general as it was observed in both AD and DLB. In contrast, the loss of global efficiency variability in DLB might indicate the presence of an abnormally rigid brain network and the lack of economical dynamics, factors which could contribute to cognitive slowing and an inability to respond appropriately to situational demands.
Highlights
Resting state functional MRI has been used to study changes in functional connectivity associated with different forms of dementia such as dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) (Kenny et al, 2012; Lowther et al, 2014; Peraza et al, 2014; Schumacher et al, 2018)
The aims of our study were to (1) identify the differential dynamic connectivity profile of DLB compared to healthy controls, (2) investigate how functional connectivity dynamics in DLB differ from AD, and (3) test a possible relation between abnormal connectivity dynamics and the severity of clinical symptoms in DLB
In terms of dynamic changes in overall network structure, we found reduced variability of global efficiency in the DLB group compared to controls which was not observed in the AD group
Summary
Resting state functional MRI has been used to study changes in functional connectivity associated with different forms of dementia such as dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) (Kenny et al, 2012; Lowther et al, 2014; Peraza et al, 2014; Schumacher et al, 2018). Most functional connectivity studies have focused on analyzing mean connectivity over the duration of a scan of several minutes, thereby implicitly assuming that functional connectivity remains stationary during that time. A large number of patients experience fluctuations in cognition and attention/arousal which are qualitatively different from the less frequently seen fluctuations in other dementias, such as AD (Bradshaw et al, 2004). In DLB, they occur mostly spontaneously without any situational explanation and result in pronounced variation in cognitive ability over time
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