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Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer's disease
Julia Schumacher1, Luis R Peraza2, Michael Firbank1
1Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
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.
Insights
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients exhibit altered brain connectivity, showing reduced efficiency and difficulty switching network states. These changes may underlie cognitive symptoms in dementia.
Area of Science:
- Neuroscience
- Cognitive Neurology
- Medical Imaging
Background:
- Dynamic functional connectivity (dFC) alterations are implicated in neurodegenerative diseases.
- Understanding dFC differences between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is crucial for differential diagnosis and treatment.
Purpose of the Study:
- To investigate and compare the dFC profiles of DLB and AD patients against healthy controls.
- To explore the relationship between dFC alterations and transient clinical symptoms in DLB.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) data from 31 DLB, 29 AD, and 31 control participants.
- Dual regression for between-network functional connectivity analysis.
- Sliding window approach, k-means clustering, and dynamic network analyses to assess dFC.
Main Results:
- Both AD and DLB patients spent more time in states of sparse connectivity and motor network isolation compared to controls.
- DLB patients exhibited reduced time in highly connected states and diminished variability in global brain network efficiency.
- No significant correlations were found between dFC measures and clinical symptom severity.
Conclusions:
- Impaired ability to transition between connectivity states may be a general feature of dementia (AD and DLB).
- Reduced global efficiency variability in DLB suggests a rigid brain network, potentially contributing to cognitive slowing and impaired situational responses.