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Download joie future7/27/2023 The development of in vivo Aβ and tau biomarkers has greatly facilitated diagnosing AD however, a reliable prognosis of AD-related cognitive decline in clinical settings remains a critical yet unmet challenge. 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.īeta-amyloid (Aβ) and tau are hallmark pathologies of Alzheimer’s disease (AD), ensuing neurodegeneration, cognitive decline, and dementia. 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. 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. Resultsīaseline global tau-PET SUVRs explained more variance (partial R 2) in future cognitive decline than Centiloid across all cognitive tests (Cohen’s d ~ 2, all tests p < 0.001) and diagnostic groups. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. amyloid effects, analyses were further controlled for the contrary PET-tracer. Centiloid on subsequent cognitive decline. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. 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 Braak 0/Braak I+/Braak I–IV+/Braak I–VI+/Braak atypical+. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. 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. 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.
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