TY  - JOUR
AU  - Biel, Davina
AU  - Brendel, Matthias
AU  - Rubinski, Anna
AU  - Bürger, Katharina
AU  - Janowitz, Daniel
AU  - Dichgans, Martin
AU  - Franzmeier, Nicolai
TI  - Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals.
JO  - Alzheimer's research & therapy
VL  - 13
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2021-01362
SP  - 137
PY  - 2021
N1  - CC BY
AB  - 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.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.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 < 0.001) and diagnostic groups. Associations between tau-PET and cognitive decline remained consistent when controlling for Centiloid, while associations between amyloid-PET and cognitive decline were non-significant when controlling for tau-PET. More advanced Braak-stage was associated with gradually worsening future cognitive decline, independent of Centiloid or diagnostic group (p < 0.001), and elevated conversion risk to MCI/dementia.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.
KW  - Aged
KW  - Alzheimer Disease: complications
KW  - Alzheimer Disease: diagnostic imaging
KW  - Amyloid beta-Peptides
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Humans
KW  - Longitudinal Studies
KW  - Positron-Emission Tomography
KW  - Prognosis
KW  - tau Proteins
KW  - Alzheimer’s disease (Other)
KW  - Amyloid-PET (Other)
KW  - Braak-staging (Other)
KW  - Conversion risk (Other)
KW  - Tau-PET (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34384484
C2  - pmc:PMC8361801
DO  - DOI:10.1186/s13195-021-00880-x
UR  - https://pub.dzne.de/record/162705
ER  -