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Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals

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Název:	Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals
Autoři:	Nicolai Franzmeier, Davina Biel, Daniel Janowitz, Matthias Brendel, Martin Dichgans, Katharina Buerger, Anna Rubinski, Alzheimer’s Disease Neuroimaging Initiative
Zdroj:	Alzheimers Res Ther Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-13 (2021) Alzheimer's research & therapy 13(1), 137 (2021). doi:10.1186/s13195-021-00880-x
Informace o vydavateli:	Springer Science and Business Media LLC, 2021.
Rok vydání:	2021
Témata:	diagnostic imaging [Cognitive Dysfunction], Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, 03 medical and health sciences, Braak-staging, 0302 clinical medicine, Alzheimer Disease, Humans, Cognitive Dysfunction, ddc:610, Longitudinal Studies, RC346-429, Aged, Amyloid beta-Peptides, Research, complications [Alzheimer Disease], Prognosis, Conversion risk, Aged [MeSH], Humans [MeSH], Amyloid beta-Peptides [MeSH], Alzheimer Disease/diagnostic imaging [MeSH], Longitudinal Studies [MeSH], Alzheimer's disease, Tau-PET, Cognitive Dysfunction/diagnostic imaging [MeSH], Prognosis [MeSH], tau Proteins [MeSH], Positron-Emission Tomography [MeSH], Alzheimer Disease/complications [MeSH], Amyloid-PET, 3. Good health, Positron-Emission Tomography, Neurology. Diseases of the nervous system, diagnostic imaging [Alzheimer Disease], RC321-571
Popis:	Background To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment. Methods In this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(−) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI–IV+/BraakI–VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. Results Baseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen’s d ~ 2, all tests p p Conclusion Tau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.
Druh dokumentu:	Article Other literature type
Jazyk:	English
ISSN:	1758-9193
DOI:	10.1186/s13195-021-00880-x
Přístupová URL adresa:	https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-021-00880-x https://pubmed.ncbi.nlm.nih.gov/34384484 https://doaj.org/article/ab4e042725fe4abf8baf8cbc4806face https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00880-x https://link.springer.com/content/pdf/10.1186/s13195-021-00880-x.pdf https://pubmed.ncbi.nlm.nih.gov/34384484/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361801 https://pub.dzne.de/record/162705 https://repository.publisso.de/resource/frl:6464025 https://epub.ub.uni-muenchen.de/90959/ https://epub.ub.uni-muenchen.de/97029/
Rights:	CC BY
Přístupové číslo:	edsair.doi.dedup.....1dca8bb398fb47ba890eda6390eba907
Databáze:	OpenAIRE

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Abstrakt:	Background To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment. Methods In this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(−) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI–IV+/BraakI–VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. Results Baseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen’s d ~ 2, all tests p p Conclusion Tau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.
ISSN:	17589193
DOI:	10.1186/s13195-021-00880-x