Abstract
ObjectivesFunctional 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. MethodsEEG 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. ResultsSmall-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. ConclusionsTemporal lobe disconnection plays a key role in cognitive impairment in AD. SignificanceWe combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.
Highlights
Introduction⇑ Corresponding author at: Living Systems Institute, University of Exeter, Exeter, Alzheimer’s Disease (AD) is the most common disease causing dementia; approximately 70% of dementias have been identified to be caused by AD based on clinical diagnosis and postmortem examination of the brain (Barker et al, 2002; Bermejo-Pareja et al, 2008)
Dementia is a neurological disorder that is characterised by progressive cognitive decline; common symptoms in the early stages include memory loss, language impairments, visuospatial impairments and behavioural changes (Agronin, 2014).⇑ Corresponding author at: Living Systems Institute, University of Exeter, Exeter, Alzheimer’s Disease (AD) is the most common disease causing dementia; approximately 70% of dementias have been identified to be caused by AD based on clinical diagnosis and postmortem examination of the brain (Barker et al, 2002; Bermejo-Pareja et al, 2008)
EEG from HOA and AD patients was projected into source space using Exact low resolution brain electromagnetic tomography (eLORETA) and downsampled to 40 regions of interest (ROIs) (Table 4), see Methods
Summary
⇑ Corresponding author at: Living Systems Institute, University of Exeter, Exeter, Alzheimer’s Disease (AD) is the most common disease causing dementia; approximately 70% of dementias have been identified to be caused by AD based on clinical diagnosis and postmortem examination of the brain (Barker et al, 2002; Bermejo-Pareja et al, 2008). One of the key challenges for developing treatment methods for AD is understanding the pathological mechanisms in the brain underlying cognitive impairment.
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