Dataset Information

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

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.

SUBMITTER: Schumacher J

PROVIDER: S-EPMC6462776 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Schumacher Julia J Peraza Luis R LR Firbank Michael M Thomas Alan J AJ Kaiser Marcus M Gallagher Peter P O'Brien John T JT Blamire Andrew M AM Taylor John-Paul JP

NeuroImage. Clinical 20190403

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 ...[more]

PMID: 30991620

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Project description:Using resting-state functional magnetic resonance imaging, spontaneous low-frequency fluctuations in the blood oxygenation level-dependent signal were measured to investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer's disease and healthy controls. These included connections of the hippocampus, because of its role in learning, and parietal and occipital areas involved in memory, attention and visual processing. Connectivity was investigated in 47 subjects aged 60 years and over: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer's disease and 16 control subjects. Subjects were scanned using a 3 Tesla magnetic resonance imaging system. The mean blood oxygenation level-dependent signal time series was extracted from seed regions in the hippocampus, posterior cingulate cortex, precuneus and primary visual cortex and correlated with all other brain voxels to determine functional connectivity. Both subjects with dementia with Lewy bodies and Alzheimer's disease showed greater connectivity than control subjects. Compared with controls, the dementia with Lewy bodies group had greater connectivity between the right posterior cingulate cortex and other brain areas. In dementia with Lewy bodies, there were no significant differences in hippocampal connectivity compared with controls, but in Alzheimer's disease left hippocampal connectivity was greater compared with controls. There were no significant differences between groups for precuneus or primary visual cortex connectivity. No seed regions showed significantly less connectivity in subjects with dementia with Lewy bodies or Alzheimer's disease compared with controls. We found greater connectivity with the posterior cingulate in dementia with Lewy bodies and with the hippocampus in Alzheimer's disease. Consistent with the known relative preservation of memory in dementia with Lewy bodies compared with Alzheimer's disease, hippocampal connectivity was not found to be greater in dementia with Lewy bodies. Importantly, while metabolic imaging shows functional change in primary visual cortex in dementia with Lewy bodies, which is hypothesized to account for visual hallucinations, we found connectivity with this region to be unaffected. This implicates areas beyond visual sensory input level in the visual symptoms and visual-perceptual dysfunction seen in dementia with Lewy bodies.

Project description:Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.

Project description:BackgroundFluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). They represent a determining factor for its diagnosis and strongly impact the quality of life of patients and their caregivers. However, the neural correlates of this complex symptom remain poorly understood. This study aimed to investigate the structural and functional changes in DLB patients, compared to Alzheimer's disease (AD) patients and healthy elderly subjects, and their potential links with fluctuations.MethodsStructural and resting-state functional MRI data were collected from 92 DLB patients, 70 AD patients, and 22 control subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. Gray matter volume changes were analyzed using whole-brain voxel-based morphometry, and resting-state functional connectivity was investigated using a seed-based analysis, with regions of interest corresponding to the main nodes of the salience network (SN), frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN).ResultsAt the structural level, fluctuation scores in DLB patients did not relate to the atrophy of insular, temporal, and frontal regions typically found in this pathology, but instead showed a weak correlation with more subtle volume reductions in different regions of the cholinergic system. At the functional level, the DLB group was characterized by a decreased connectivity within the SN and attentional networks, while the AD group showed decreases within the SN and DMN. In addition, higher fluctuation scores in DLB patients were correlated to a greater connectivity of the SN with the DAN and left thalamus, along with a decreased connectivity between the SN and DMN, and between the right thalamus and both the FPN and DMN.ConclusionsFunctional connectivity changes, rather than significant gray matter loss, could play an important role in the emergence of fluctuations in DLB. Notably, fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the SN, which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli. Our results also suggest that the thalamus could be a key region for the occurrence of this symptom.

Project description:Attention and executive dysfunction are features of Lewy body dementia (LBD) but their neuroanatomical basis is poorly understood. To investigate underlying dysfunctional attention-executive network (EXEC) interactions, we examined functional connectivity (FC) in 30 patients with LBD, 20 patients with Alzheimer's disease (AD), and 21 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a modified Attention Network Test (ANT), where they were instructed to press a button in response to the majority direction of arrows, which were either all pointing in the same direction or with one pointing in the opposite direction. Network activations during both target conditions and a baseline condition (no target) were derived by (ICA) Independent Component Analysis, and interactions between these networks were examined using the beta series correlations approach. Our study revealed that FC of ventral and dorsal attention networks DAN was reduced in LBD during all conditions, although most prominently during incongruent trials. These alterations in connectivity might be driven by a failure of engagement of ventral attention networks, and consequent over-reliance on the DAN. In contrast, when comparing AD patients with the other groups, we found hyperconnectivity between the posterior part of the default mode network (DMN) and the DAN in all conditions, particularly during incongruent trials. This might be attributable to either a compensatory effect to overcome DMN dysfunction, or be arising as a result of a disturbed transition of the DMN from rest to task. Our results demonstrate that dementia syndromes can be characterized both by hyper- and hypoconnectivity of distinct brain networks, depending on the interplay between task demand and available cognitive resources. However these are dependent upon the underlying pathology, which needs to be taken into account when developing specific cognitive therapies for LBD as compared to Alzheimer's.

Project description:Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α-synuclein aggregates, but many DLB cases show concurrent Alzheimer's disease pathology in the form of amyloid-β plaques and tau neurofibrillary tangles. The first objective of this study was to investigate the effect of Alzheimer's disease co-pathology on functional network changes within the default mode network (DMN) in DLB. Second, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Twenty-seven DLB, 26 Alzheimer's disease and 99 cognitively unimpaired participants (balanced on age and sex to the DLB group) underwent tau-PET with AV-1451 (flortaucipir), amyloid-β-PET with Pittsburgh compound-B (PiB) and resting-state functional MRI scans. The resing-state functional MRI data were used to assess functional connectivity within the posterior DMN. This was then correlated with overall cortical flortaucipir PET and PiB PET standardized uptake value ratio (SUVr). The strength of interregional functional connectivity was assessed using the Schaefer atlas. Tau-PET covariance was measured as the correlation in flortaucipir SUVr between any two regions across participants. The association between region-to-region functional connectivity and tau-PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot- and cold spots) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot and cold spots. A reduction in posterior DMN connectivity correlated with overall higher cortical tau- (r = -0.39, P = 0.04) and amyloid-PET uptake (r = -0.41, P = 0.03) in the DLB group, i.e. patients with DLB who have more concurrent Alzheimer's disease pathology showed a more severe loss of DMN connectivity. Higher functional connectivity between regions was associated with higher tau covariance in cognitively unimpaired, Alzheimer's disease and DLB. Furthermore, higher functional connectivity of a target region to the tau hotspot (i.e. inferior/medial temporal cortex) was related to higher flortaucipir SUVrs in the target region, whereas higher functional connectivity to the tau cold spot (i.e. sensory-motor cortex) was related to lower flortaucipir SUVr in the target region. Our findings suggest that a higher burden of Alzheimer's disease co-pathology in patients with DLB is associated with more Alzheimer's disease-like changes in functional connectivity. Furthermore, we found an association between the brain's functional network architecture and the distribution of tau pathology that has recently been described in Alzheimer's disease. We show that this relationship also exists in patients with DLB, indicating that similar mechanisms of connectivity-dependent occurrence of tau pathology might be at work in both diseases.

Dataset Information

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

Publications

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

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