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Cognitive changes of older adults with an equivocal amyloid load

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Abstract

Background

Observational and interventional studies addressing the link between amyloid (Aβ) burden and cognitive decline are increasing, but a clear definition of amyloid positivity is still lacking. This may represent a great stake for therapeutic studies enrolling Aβ + patients only. The main objective of this study was to define a population with “equivocal” amyloid status, and evaluate their cognitive changes.

Methods

Sixty-five participants over 75 years old, from the Control group of the interventional MAPT study, at risk to develop Alzheimer’s disease, were included. Participants were classified into three groups in terms of amyloid load: Aβ +, Aβ − and Equivocal participants (according to visual reading, global standardized uptake (SUVR) cut-offs, or a k-mean clustering method). The cognitive changes over time (memory, executive functions, attention and processing speed) of this Equivocal group were then compared to Aβ + and Aβ − participants.

Results

When classified by visual read, Equivocal participants’ memory scores were comparable to the Aβ- participants, and greater than in Aβ + participants over time. Secondary analyses, using SUVR cut-offs classification, showed different trajectories with Equivocal participants being comparable to the Aβ + participants, and lower than Aβ-, on executive performance over time.

Conclusions

This original work pointed out a population that may be of great interest for interventional studies, raising the question of how amyloid status should be defined and integrated in such studies. These findings should be replicated in future studies on larger datasets, to confirm what methodological approach would be the most suitable to highlight this specific neuroimaging entity.

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Acknowledgements

This study was supported by grants from the French Ministry of Health (PHRC 2008), and the Institut de Recherche Pierre Fabre. The promotion of this study was supported by the University Hospital Center of Toulouse. Biological sample collection was supported by Exhonit Therapeutics. The AV45-MAPT study was supported by Avid radiopharmaceuticals/Eli Lilly and Company. Authors would like to thank all the members of the MAPT/DSA Study Group.

Funding

This work was funded by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute, Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc.

Author information

Author notes

  1. Kristell Pothier and Laure Saint-Aubert authors have contributed equally to this work.

Authors and Affiliations

  1. Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse (CHU Toulouse), Toulouse, France

    Kristell Pothier, Claudie Hooper, Julien Delrieu, Philipe de Souto Barreto & Bruno Vellas

  2. EA 2114, Département de Psychologie-Psychologie des Ages de la Vie et Adaptation, University of Tours, 3, Rue des Tanneurs, 37041, Tours Cedex 1, France

    Kristell Pothier

  3. Department of Nuclear Medicine, Imaging Pole, Toulouse University Hospital, Toulouse, France

    Laure Saint-Aubert & Pierre Payoux

  4. Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France

    Laure Saint-Aubert, Julien Delrieu & Pierre Payoux

  5. UMR INSERM 1027, University of Toulouse III, Toulouse, France

    Philipe de Souto Barreto & Bruno Vellas

Authors
  1. Kristell Pothier
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  2. Laure Saint-Aubert
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  4. Julien Delrieu
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  5. Pierre Payoux
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  6. Philipe de Souto Barreto
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  7. Bruno Vellas
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MAPT/DSA Study Group

Corresponding author

Correspondence to Kristell Pothier.

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Conflicts of interest

Prof. P. Payoux served on the scientific advisory board of Avid Radiopharmaceuticals and GEHC. Dr. J. Delrieu served on the scientific advisory board of Avid Radiopharmaceuticals. Prof. B. Vellas served on the scientific advisory board of Avid Radiopharmaceuticals. Other authors (Dr K. Pothier, Dr L. Saint-Aubert, Dr C. Hooper, Dr de Souto Baretto) declare that they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Pothier, K., Saint-Aubert, L., Hooper, C. et al. Cognitive changes of older adults with an equivocal amyloid load. J Neurol 266, 835–843 (2019). https://doi.org/10.1007/s00415-019-09203-5

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  • DOI: https://doi.org/10.1007/s00415-019-09203-5

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