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Neuropsychiatric symptoms in limbic-predominant age-related TDP-43 encephalopathy and Alzheimer's disease

Lookup NU author(s): Dr Kirsty McAleese, Professor Johannes Attems, Professor Alan ThomasORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.There is clinical overlap between presentations of dementia due to limbic-predominant age-related TDP-43 encephalopathy (LATE) and Alzheimer's disease. It has been suggested that the combination of Alzheimer's disease neuropathological change (ADNC) and LATE neuropathological changes (LATE-NC) is associated with greater neuropsychiatric symptom burden, compared to either pathology alone. Longitudinal Neuropsychiatric Inventory and psychotropic medication prescription data from neuropathologically diagnosed pure ADNC (n = 78), pure LATE-NC (n = 14) and mixed ADNC/LATE-NC (n = 39) brain bank donors were analysed using analysis of variance and linear mixed effects regression models to examine the relationship between diagnostic group and neuropsychiatric symptom burden. Nearly all donors had dementia; three (two pure LATE-NC and one pure ADNC) donors had mild cognitive impairment and another two donors with LATE-NC did not have dementia. The mixed ADNC/LATE-NC group was older than the pure ADNC group, had a higher proportion of females compared to the pure ADNC and LATE-NC groups, and had more severe dementia versus the pure LATE-NC group. After adjustment for length of follow-up, cognitive and demographic factors, mixed ADNC/LATE-NC was associated with lower total Neuropsychiatric Inventory and agitation factor scores than pure ADNC, and lower frontal factor scores than pure LATE-NC. Our findings indicate that concomitant LATE pathology in Alzheimer's disease is not associated with greater neuropsychiatric symptom burden. Future longitudinal studies are needed to further investigate whether mixed ADNC/LATE-NC may be protective against agitation and frontal symptoms in dementia caused by Alzheimer's disease or LATE pathology.

Publication metadata

Author(s): Liu KY, Reeves S, McAleese KE, Attems J, Francis P, Thomas A, Howard R

Publication type: Article

Publication status: Published

Journal: Brain : a journal of neurology

Year: 2020

Volume: 143

Issue: 12

Pages: 3842-3849

Print publication date: 01/12/2020

Online publication date: 14/11/2020

Acceptance date: 31/07/2020

Date deposited: 16/02/2021

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awaa315

PubMed id: 33188391


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