title: A Conceptualization of the Utility of Subjective Cognitive Decline in Clinical Trials of Preclinical Alzheimer's Disease.
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.
authors: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia. rfbuckley@mgh.harvard.edu.|Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia. rfbuckley@mgh.harvard.edu.|Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham Women's Hospital/Harvard Medical School, Boston, MA, USA. rfbuckley@mgh.harvard.edu.|Athinoula A. Martinos Center for Biomedical Imaging, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. rfbuckley@mgh.harvard.edu.
authors: Rachel F
authors: RF
authors: Buckley
authors: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.|Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.|Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia.
authors: Victor L
authors: VL
authors: Villemagne
authors: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
authors: Colin L
authors: CL
authors: Masters
authors: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.|The Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Australia.
authors: Kathryn A
authors: KA
authors: Ellis
authors: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.|Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia.
authors: Christopher C
authors: CC
authors: Rowe
authors: Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham Women's Hospital/Harvard Medical School, Boston, MA, USA.|Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors: Keith
authors: K
authors: Johnson
authors: Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham Women's Hospital/Harvard Medical School, Boston, MA, USA.|Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors: Reisa
authors: R
authors: Sperling
authors: Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham Women's Hospital/Harvard Medical School, Boston, MA, USA.|Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors: Rebecca
authors: R
authors: Amariglio
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000592:standards*; D003071:Cognition; D059026:Diagnostic Self Evaluation; D006801:Humans
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; Amyloid; Cognition; Preclinical; Subjective cognitive decline; Tau