Thomas, DX;
Bajaj, S;
McRae-McKee, K;
Hadjichrysanthou, C;
Anderson, RM;
Collinge, J;
(2020)
Association ofTDP‑43
proteinopathy, cerebral
amyloid angiopathy, and Lewy
bodies with cognitive
impairment in individuals
with or withoutAlzheimer’s disease
neuropathology.
Scientific Reports
, 10
(1)
, Article 14579. 10.1038/s41598-020-71305-2.
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Abstract
Alzheimer's disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer's disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer's disease neuropathology. Within our study population, 63% of individuals given the 'gold-standard' neuropathological diagnosis of Alzheimer's disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer's disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer's disease-related processes may have severely limited efficacy in these co-morbid populations.
| Type: | Article |
|---|---|
| Title: | Association ofTDP‑43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or withoutAlzheimer’s disease neuropathology |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-71305-2 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-020-71305-2 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Alzheimer's disease, Neurodegenerative diseases, Neurology, Neuroscience, Statistics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10110461 |
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