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Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters



[18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer’s disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker “mismatches.”


Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker “mismatches”). We also investigated associations between “mismatches” and sociodemographic and educational characteristics.


AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A− (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as “SNAP” and one as probable frontotemporal lobar degeneration. All A− (N)− cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES).


The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker “mismatches.” An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

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This work was supported by the São Paulo Research Foundation (FAPESP) in Brazil, reference number 2012/50239-6. The authors thank the staff of the Departments of Neurology and Psychiatry of the University of Sao Paulo Medical School for the selection and referral of the patients, and the staff of the Nuclear Medicine Center of the Institute of Radiology for the technical support.


This study was funded by the São Paulo Research Foundation (FAPESP) in Brazil, reference number 2012/50239-6.

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Correspondence to Artur Martins Coutinho.

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Artur Martins Coutinho declares that he has no conflicts of interest.

Fábio Henrique de Gobbi Porto has received a speaker honorarium from Libbs, Lundbeck, and Sandoz-Novartis.

Daniele de Paula Faria declares that she has no conflicts of interest.

Carla Rachel Ono declares that she has no conflicts of interest.

Alexandre Teles Garcez declares that he has no conflicts of interest.

Paula Squarzoni declares that she has no conflicts of interest.

Fábio Luiz de Souza Duran declares that he has no conflicts of interest.

Maira Okada de Oliveira declares that she has no conflicts of interest.

Eduardo Sturzeneker Tres declares that he has no conflicts of interest.

Sonia Maria Dozzi Brucki declares that she has no conflicts of interest.

Orestes Vicente Forlenza declares that he has no conflicts of interest.

Ricardo Nitrini declares that he has no conflicts of interest.

Geraldo Busatto Filho declares that he has no conflicts of interest.

Carlos Alberto Buchpiguel declares that he has no conflicts of interest.

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Coutinho, A.M., Busatto, G.F., de Gobbi Porto, F.H. et al. Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters. Eur J Nucl Med Mol Imaging (2020). https://doi.org/10.1007/s00259-020-04714-0

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  • Positron-emission tomography
  • Fluorodeoxyglucose F18
  • Amyloid
  • Amyloid beta-peptides
  • Cognitive dysfunction
  • Alzheimer’s disease
  • Education