Brain network connectivity differs in early-onset neurodegenerative dementia

Filippi, Massimo; Basaia, Silvia; Canu, Elisa; Imperiale, Francesca; Meani, Alessandro; Caso, Francesca; Magnani, Giuseppe; Falautano, Monica; Comi, Giancarlo; Falini, Andrea

doi:10.1212/wnl.0000000000004577

Cited by 97 publications

(101 citation statements)

References 41 publications

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“…Previously, we proposed a mesoscale brain network model that anatomically and functionally linked the DMN to the ON via the hippocampus [55]. That model, supported by the findings of the current study ( Figure 5), may help differentiate patterns of olfactory deficits and their development in AD progression, leading to new studies of AD pathophysiology focusing on coupling impairments affecting network dynamics [56].…”

Section: Discussionsupporting

confidence: 79%

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Testa

Jordan

et al. 2019

Brain Sciences

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Olfactory impairment is associated with prodromal Alzheimer’s disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other temporal lobe structures. This selective vulnerability suggests that the functional connectivity (FC) between the olfactory network (ON), consisting of the POC, insula and orbital frontal cortex (OFC) (Tobia et al., 2016), and the hippocampus may be impaired in early stage AD. Yet, the development trajectory of this potential FC impairment remains unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate FC changes between the ON and hippocampus in four groups: aged-matched cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. FC was calculated using low frequency fMRI signal fluctuations in the ON and hippocampus (Tobia et al., 2016). We found that the FC between the ON and the right hippocampus became progressively disrupted across disease states, with significant differences between EMCI and LMCI groups. Additionally, there were no significant differences in gray matter hippocampal volumes between EMCI and LMCI groups. Lastly, the FC between the ON and hippocampus was significantly correlated with neuropsychological test scores, suggesting that it is related to cognition in a meaningful way. These findings provide the first in vivo evidence for the involvement of FC between the ON and hippocampus in AD pathology. Results suggest that functional connectivity (FC) between the olfactory network (ON) and hippocampus may be a sensitive marker for Alzheimer’s disease (AD) progression, preceding gray matter volume loss.

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Section: Discussionsupporting

confidence: 79%

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Testa

Jordan

et al. 2019

Brain Sciences

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“…Together, these findings are in line with the notion that neurodegeneration in AD spreads across functional networks (Lehmann et al., ). Thus, the proposed model may have the ability to differentiate patterns of olfactory deficits and their trajectory, leading to new studies focusing on coupling impairments as the main cause of brain network dysfunction in AD progression (Filippi et al., ). These results suggest that understanding network integrity, combined with olfactory performance (e.g., UPSIT), may provide a more precise measure to improve prediction of cognitive ability in AD .…”

Section: Discussionmentioning

confidence: 99%

“…There is ample evidence to suggest that AD neurodegeneration (atrophy) spreads and causes disruption across neural networks (Ahmed et al., ; Bede, ; Filippi et al., ; Guo et al., ). Therefore, this study focused on testing a human model of AD neurodegeneration‐to‐olfactory impairment to evaluate a mechanistic account of how AD progression can concurrently disrupt the integrity of the ON‐DMN network.…”

Section: Introductionmentioning

confidence: 99%

Disruptions of the olfactory and default mode networks in Alzheimer's disease

Yang

Zhang

et al. 2019

Brain and Behavior

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Introduction Olfactory deficits are prevalent in early Alzheimer's disease (AD) and are predictive of progressive memory loss and dementia. However, direct neural evidence to relate AD neurodegeneration to deficits in olfaction and memory is limited. Methods We combined the University of Pennsylvania Smell Identification Test (UPSIT) with olfactory functional magnetic resonance imaging (fMRI) to investigate links between neurodegeneration, the olfactory network (ON) and the default mode network (DMN) in AD. Results Behaviorally, olfactory and memory scores showed a strong positive correlation in the study cohorts. During olfactory fMRI, the ON showed reduced task‐related activation and the DMN showed reduced task‐related suppression in mild cognitive impairment (MCI) and AD subjects compared to age‐matched cognitively normal subjects. Conclusions The results provide in vivo evidence for selective vulnerability of ON and DMN in AD and significantly improves the viable clinical applications of olfactory testing. A network‐based approach, focusing on network integrity rather than focal pathology, seems beneficial to olfactory prediction of dementia in AD.

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“…The “network degeneration hypothesis” suggests that AD-related pathology initiates in and propagates along specific neuronal populations that follow the trajectory of intrinsic structural or functional brain networks (Palop, et al, 2006; Seeley, et al, 2009; Tahmasian, et al, 2016). Thus, reduced efficacy of long-distance functional connections of the DMN (Liu, et al, 2014) and altered FC topology of hub regions within the posterior DMN and the medial temporal lobe of AD patients (Brier, et al, 2014; Filippi, et al, 2017; Sanz-Arigita, et al, 2010; Seo, et al, 2013; Supekar, et al, 2008), suggest in a “network-based” degeneration pattern for FC topology in AD. Based on this hypothesis it could be speculated that regional AD pathology, namely amyloid, underlies the overlapping patterns of rFDG and FC topology disruption.…”

Section: Discussionmentioning

confidence: 99%

Decoupling of inter-regional functional connectivity and regional neural activity in Alzheimer Disease

Maleki-Balajoo

Rahmani²,

Khosrowabadi

et al. 2019

Preprint

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199/200)Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). It is, however, poorly understood how changes in regional neural activity and inter-regional FC interact in AD and MCI. Here, we investigated the link between regional neural activity and nodal topological measures of FC through simultaneous PET/MR measurement in 20 patients with MCI, 33 patients with AD, and 26 healthy individuals. First, we assessed regional glucose metabolism identified through FDG-PET (rFDG) (as a proxy of regional neural activity), and regional FC topology through clustering coefficient (CC) and degree centrality (DC) (as surrogates of local segregation and global connectivity, respectively). Next, we examined the potential moderating effect of disease status (AD or MCI) on the link between rFDG and FC topology using hierarchical moderated multiple regression analysis. Alterations in rFDG, CC, and DC were widespread in patients, and AD alters physiological coupling between regional metabolism and functional connectivity particularly in the inferior temporal gyus and supplementary motor areas. While rFDG correlated with CC in healthy subjects, this correlation was lost in AD patients. We suggest that AD pathology decouples the normal association between regional neural activity and functional segregation.

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Brain network connectivity differs in early-onset neurodegenerative dementia

Cited by 97 publications

References 41 publications

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Disruptions of the olfactory and default mode networks in Alzheimer's disease

Decoupling of inter-regional functional connectivity and regional neural activity in Alzheimer Disease

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