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A Conceptualization of the Utility of Subjective Cognitive Decline in Clinical Trials of Preclinical Alzheimer’s Disease

Journal of Molecular Neuroscience volume 60, pages 354–361 (2016)Cite this article

Abstract

This commentary outlines a conceptual model for subjective cognitive decline (SCD) in relation to Alzheimer’s disease (AD) biomarkers in the preclinical stages of disease and a framework for effectively utilizing SCD in secondary prevention clinical trials. Mounting evidence supports the notion that SCD is sensitive to encroaching Aβ-amyloid and neurodegeneration. SCD has also been shown to provide additive information of AD-dementia risk beyond what is known about the biomarker status of the individual. Thus, we provide recommendations for the implementing SCD measurement in clinical trials. We argue that SCD can be measured at three catch points within the course of the clinical trial: firstly, at the initial recruitment and screening phase; secondly, to create more robust estimates of rates of AD-dementia progression; and finally, to measure subjective experiences of cognitive change and quality of life over the course of the trial as a proxy of clinically meaningful functional improvement. We provide recommendations of how SCD can be approached at each of these points. SCD is an important component of the preclinical AD-dementia trajectory. Future studies need to elucidate the interactive influence of Aβ-amyloid and tau on SCD from a spatiotemporal perspective. Even as this evidence accrues, it is clear that SCD can provide unique and additive information about rates of progression and subjectively experienced cognitive change within clinical trials.

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Acknowledgments

Dr. Buckley is funded by the National Medical and Health Research Council (NHMRC) Dementia Research Fellowship (APP1105576).

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Affiliations

  1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia

    Rachel F. Buckley, Victor L. Villemagne, Colin L. Masters & Kathryn A. Ellis

  2. Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia

    Rachel F. Buckley

  3. Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham Women’s Hospital/Harvard Medical School, Boston, MA, USA

    Rachel F. Buckley, Keith Johnson, Reisa Sperling & Rebecca Amariglio

  4. Athinoula A. Martinos Center for Biomedical Imaging, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Rachel F. Buckley

  5. Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia

    Victor L. Villemagne & Christopher C. Rowe

  6. Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia

    Victor L. Villemagne & Christopher C. Rowe

  7. The Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Australia

    Kathryn A. Ellis

  8. Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

    Keith Johnson, Reisa Sperling & Rebecca Amariglio

  9. Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

    Keith Johnson

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  1. Rachel F. Buckley
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  2. Victor L. Villemagne
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  3. Colin L. Masters
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  5. Christopher C. Rowe
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  6. Keith Johnson
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  8. Rebecca Amariglio
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Correspondence to Rachel F. Buckley.

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Buckley, R.F., Villemagne, V.L., Masters, C.L. et al. A Conceptualization of the Utility of Subjective Cognitive Decline in Clinical Trials of Preclinical Alzheimer’s Disease. J Mol Neurosci 60, 354–361 (2016). https://doi.org/10.1007/s12031-016-0810-z

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  • DOI: https://doi.org/10.1007/s12031-016-0810-z

Keywords

  • Cognition
  • Subjective cognitive decline
  • Preclinical
  • Alzheimer’s disease
  • Amyloid
  • Tau