Amyloid-beta in the insular cortex is associated with cognitive fluctuations in dementia with Lewy bodies

Alice Oliver-Evans, Daniel Erskine, Mary Johnson, Johannes Attems, Ahmad Khundakar, Alan Jeffrey Thomas

Research output: Contribution to journalConference articlepeer-review


Introduction: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB) and are related to a reduced capacity for independent living. The anterior insular cortex has been associated with the processing of cognitive information, with atrophy previously described in DLB patients. Layer five of the anterior insula contains specific neuronal sub-types that are implicated in cognitive integration, processing and output to cortical and subcortical regions; and whose disruption has been associated with cognitive disturbances. In this study we aimed to assess pathological changes within layer five of the anterior insula in DLB compared with other neurodegenerative disorders and to correlate against clinical neuropsychiatric data.

Material and methods: Quantitative neuropathological analysis was used to assess, alpha-synuclein, amyloid-beta and tau pathology, in DLB (n = 15), Alzheimer's disease (AD) (n = 16), Parkinson's disease (n = 9), Parkinson's disease with dementia (n = 7) and controls (n = 16). Neuropathological data was correlated with clinical data to evaluate the relationship between neuropathological changes and clinical phenotype.

Results: In DLB only an increased amyloid-beta burden was associated with the presence of cognitive fluctuations (P < 0.05) and a lower mini-mental state examination score (P < 0.05), indicative of a greater cognitive decline. No association was observed between alpha-synuclein or tau burden and cognitive fluctuations.

Conclusion: The findings suggest that although DLB is defined by the presence of alpha-synuclein pathology, in the anterior insula amyloid-beta pathology may contribute to cognitive fluctuations in DLB. Amyloid-beta may contribute to cognitive fluctuations by disrupting specific cognitive integration and relay neurons found in the insula. These findings further demonstrate the importance of AD-type pathology in the clinical manifestations of DLB and highlight the role played by multiple pathologies in age-related neurodegeneration.
Original languageEnglish
Article numberP02
Pages (from-to)30
Number of pages1
JournalNeuropathology and Applied Neurobiology
Issue numberS1
Publication statusPublished - 1 Mar 2018


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