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January 06, 2021Article

Validation of the Alzheimer Disease Dementia Conversion-Related Pattern as an ATN Biomarker of Neurodegeneration

View ORCID ProfileGanna Blazhenets, View ORCID ProfileLars Frings, Yilong Ma, Arnd Sörensen, David Eidelberg, Jens Wiltfang, Philipp T Meyer, for the Alzheimer’s Disease Neuroimaging Initiative
First published January 6, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011521
Ganna Blazhenets
1Ganna Blazhenets, Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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  • ORCID record for Ganna Blazhenets
Lars Frings
2Lars Frings, Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Yilong Ma
3Yilong Ma, Center for Neurosciences, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
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Arnd Sörensen
4Arnd Sörensen, Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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David Eidelberg
5David Eidelberg, Center for Neurosciences, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
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Jens Wiltfang
6Jens Wiltfang, Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University, Göttingen, Germany
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Philipp T Meyer
7Philipp T. Meyer, Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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Citation
Validation of the Alzheimer Disease Dementia Conversion-Related Pattern as an ATN Biomarker of Neurodegeneration
Ganna Blazhenets, Lars Frings, Yilong Ma, Arnd Sörensen, David Eidelberg, Jens Wiltfang, Philipp T Meyer, for the Alzheimer’s Disease Neuroimaging Initiative
Neurology Jan 2021, 10.1212/WNL.0000000000011521; DOI: 10.1212/WNL.0000000000011521

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Abstract

Objective: To determine whether the Alzheimer’s disease dementia conversion-related pattern (ADCRP) on [18F]FDG PET can serve as a valid predictor for the development of Alzheimer’s disease dementia, the individual expression of the ADCRP (subject score) and its prognostic value were examined in subjects with mild cognitive impairment and biologically defined Alzheimer’s disease.

Methods: 269 subjects with available [18F]FDG PET, [18F]AV-45 PET, phosphorylated and total tau in CSF, and neurofilament light chain in plasma were included. Following the AT(N) classification scheme, where Alzheimer’s disease is defined biologically by in vivo biomarkers of Aβ deposition (“A”) and pathological tau (“T”), subjects were categorized to the A-T-, A+T-, A+T+ (Alzheimer’s disease), and A-T+ groups.

Results: The mean subject score of the ADCRP was significantly higher in the A+T+ group compared to each of the other group (all p < 0.05) but was similar among the latter (all p > 0.1). Within the A+T+ group, the subject score of ADCRP was a significant predictor of conversion to dementia (HR = 2.02 per z-score increase, p < 0.001), with higher predictive value than of alternative biomarkers of neurodegeneration (total tau and neurofilament light chain). Stratification of A+T+ subjects by the subject score of ADCRP yielded well-separated groups of high, medium, and low conversion risks.

Conclusions: The ADCRP is a valuable biomarker of neurodegeneration in subjects with mild cognitive impairment and biologically defined Alzheimer’s disease. It shows great potential for stratifying the risk and estimating the time to conversion to dementia in subjects with mild cognitive impairment and underlying Alzheimer’s disease (A+T+).

Classification of Evidence: This study provides Class I evidence that [18F]FDG PET predicts the development of AD dementia in individuals with MCI and underlying AD as defined by the AT(N) framework.

  • Received May 22, 2020.
  • Accepted in final form November 9, 2020.
  • © 2021 American Academy of Neurology

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