Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94

Michalowska, Malgorzata M., Herholz, Karl, Hinz, Rainer, Amadi, Chinenye, McInnes, Lynn, Anton-Rodriguez, Jose M., Karikari, Thomas K., Blennow, Kaj, Zetterberg, Henrik, Ashton, Nicholas J., Pendleton, Neil and Carter, Stephen F. (2022) Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94. Molecular Psychiatry. ISSN 1359-4184 (In Press)

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Official URL: https://doi.org/10.1038/s41380-022-01685-6

Abstract

Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aβ. Good correspondence existed between binary (+/-) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8-17% of individuals being unstageable, i.e., not following the sequential progression of Aβ deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aβ, thus, it remains an open topic what constitutes abnormal brain Aβ in the oldest-old and what is the best method to determine that.

Item Type: Article
Additional Information: Funding Information: This work received financial support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement no. 115372. This work also received in-kind sponsoring from GE Healthcare in the form of flutemetamol cassettes for production of the radiotracer at the Wolfson Molecular Imaging Centre using GE’s FASTlab system. This work has also been supported by the Erasmus+ programme of the European Union. The European Commission support for the production of this publication does not constitute an endorsement of the contents which reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein. SFC is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We are very grateful to the individuals who participated in this study and their long dedication to ageing research. This study also would not have been possible without operational support colleagues at the Wolfson Molecular Imaging Centre and the research nurses and radiographers at the NIHR Manchester Clinical Research Facility within Manchester Royal Infirmary.
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
C800 Psychology
Department: Faculties > Health and Life Sciences > Psychology
Depositing User: John Coen
Date Deposited: 03 Aug 2022 14:48
Last Modified: 03 Aug 2022 15:00
URI: http://nrl.northumbria.ac.uk/id/eprint/49729

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