Network substrates of cognitive impairment in Alzheimer's Disease

Luke Tait; George Stothart; Elizabeth Coulthard; J. T. Brown; Nina Kazanina; Marc Goodfellow

doi:10.1016/j.clinph.2019.05.027

Network substrates of cognitive impairment in Alzheimer's Disease

Luke Tait, George Stothart, Elizabeth Coulthard, J. T. Brown, Nina Kazanina, Marc Goodfellow

Department of Psychology

Research output: Contribution to journal › Article › peer-review

22 Citations (SciVal)

Abstract

Objectives: Functional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer's Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. Methods: EEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. Results: Small-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. Conclusions: Temporal lobe disconnection plays a key role in cognitive impairment in AD. Significance: We combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.

Original language	English
Pages (from-to)	1581-1595
Number of pages	15
Journal	Clinical Neurophysiology
Volume	130
Issue number	9
Early online date	27 Jun 2019
DOIs	https://doi.org/10.1016/j.clinph.2019.05.027
Publication status	Published - 1 Sept 2019

Funding

MG gratefully acknowledges the financial support of the EPSRC via grants EP/P021417/1 and EP/N014391/1 . MG also acknowledges the generous support of a Wellcome Trust Institutional Strategic Support Award ( https://wellcome.ac.uk/ ) via grant WT105618MA . LT’s doctoral studentship is supported by the Alzheimers Society in partnership with the Garfield Weston Foundation (grant reference 231). NK was supported by the University Research Fellowship from the University of Bristol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Appendix A

Keywords

Alzheimer's Disease
Cognitive impairment
Dementia
Electroencephalography

ASJC Scopus subject areas

Sensory Systems
Neurology
Clinical Neurology
Physiology (medical)

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title = "Network substrates of cognitive impairment in Alzheimer's Disease",

abstract = "Objectives: Functional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer's Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. Methods: EEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. Results: Small-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. Conclusions: Temporal lobe disconnection plays a key role in cognitive impairment in AD. Significance: We combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.",

keywords = "Alzheimer's Disease, Cognitive impairment, Dementia, Electroencephalography",

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AU - Stothart, George

AU - Coulthard, Elizabeth

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AU - Kazanina, Nina

AU - Goodfellow, Marc

PY - 2019/9/1

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N2 - Objectives: Functional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer's Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. Methods: EEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. Results: Small-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. Conclusions: Temporal lobe disconnection plays a key role in cognitive impairment in AD. Significance: We combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.

AB - Objectives: Functional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer's Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. Methods: EEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. Results: Small-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. Conclusions: Temporal lobe disconnection plays a key role in cognitive impairment in AD. Significance: We combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.

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Network substrates of cognitive impairment in Alzheimer's Disease

Abstract

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Keywords

ASJC Scopus subject areas

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