4.5 Article

Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer's disease

Journal

NEUROIMAGE-CLINICAL
Volume 22, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2019.101812

Keywords

Resting state fMRI; Dual regression; Sliding window; Dynamic network analysis; Neurodegeneration; Cognitive fluctuations

Categories

Funding

  1. Alzheimer's Society Doctoral Training Centre at Newcastle University
  2. Engineering and Physical Sciences Research Council of the United Kingdom [EP/K026992/1]
  3. Wellcome Trust Intermediate Clinical Fellowship [WT088441MA]
  4. Northumberland Tyne
  5. Wear NHS Foundation Trust
  6. National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre (BRC) at Newcastle upon Tyne Hospitals NHS Foundation Trust
  7. Newcastle University
  8. Alzheimer's Research UK
  9. EPSRC [EP/K026992/1] Funding Source: UKRI

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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.

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