Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study

Rachel F. Buckley, Sietske Sikkes, Victor L. Villemagne, Elizabeth C. Mormino, Jennifer S. Rabin, Samantha Burnham, Kathryn V. Papp, Vincent Doré, Colin L. Masters, Michael J. Properzi, Aaron P. Schultz, Keith A. Johnson, Dorene M. Rentz, Reisa A. Sperling, Rebecca E. Amariglio*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Introduction: We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of β-amyloid (Aβ) positron emission tomography scans required for recruiting Aβ+ clinically normal individuals in clinical trials. Methods: Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [APOE] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ+ using the SCD dichotomy, APOEε4, sex, and age. Results: SCD increased odds of Aβ+ by 1.58 relative to non-SCD. Female APOEε4 carriers with SCD exhibited higher odds of Aβ+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of Aβ positron emission tomography scans to recruit Aβ+ individuals by 13% and by 9% if APOEε4 status is known. Conclusion: SCD helps to classify those with high Aβ, even beyond the substantial effect of APOE genotype. Collecting SCD is a feasible method for targeting recruitment for those likely on the AD trajectory.

Original languageEnglish
Pages (from-to)670-678
Number of pages9
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Publication statusPublished - 1 Dec 2019


Some data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database ( ). The ADNI was launched in 2003 as a public-private partnership, led by Principal Investigator Michael W. Weiner, MD. The primary goal of ADNI has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). For up-to-date information, see . R.F.B. is funded with the NHMRC Dementia Research Fellowship (APP1105576). J.S.R. is funded by the Canadian Institutes of Health Research Postdoctoral Fellowship. This work was supported with funding from the National Institutes of Health , including P01 AG036694 (Sperling and Johnson), P50 AG005134 (Sperling, Johnson, Hedden), K23 EB019023 (Sepulcre), K23 AG049087 (Chhatwal), K24 AG035007 (Sperling), and K01 040197 (Hedden). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital , using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institutes of Health . This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers S10RR021110, S10RR023401, and S10RR023043. For ADNI , data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative ( ADNI ) ( National Institutes of Health Grant U01 AG024904), and DOD ADNI ( Department of Defense award number W81XWH-12-2-0012). ADNI is also funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: AbbVie ; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Financial disclosures: A.P.S. has been a paid consultant for Janssen Pharmaceuticals and Biogen. K.V.P. has been a paid consultant for Biogen. D.M.R. served as a consultant for Eli Lilly, Biogen Idec, and Lundbeck Pharmaceuticals and serves as a member of the Scientific Advisory Board for Neurotrack. K.A.J. has served as a paid consultant for Bayer, GE Healthcare, Janssen Alzheimer's Immunotherapy, Siemens Medical Solutions, Genzyme, Novartis, Biogen, Roche, ISIS Pharma, AZTherapies, GEHC, Lundberg, and AbbVie. He is a site coinvestigator for Lilly/Avid, Pfizer, Janssen Immunotherapy, and Navidea. He has spoken at symposia sponsored by Janssen Alzheimer's Immunotherapy and Pfizer . He receives funding from NIH grants R01EB014894, R21 AG038994, R01 AG026484, R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435, and R01 AG037497 and the Alzheimer's Association grant ZEN-10-174210. R.A.S. has served as a paid consultant for AbbVie, Biogen, Bracket, Genentech, Lundbeck, Roche, and Sanofi. She has served as a coinvestigator for Avid, Eli Lilly, and Janssen Alzheimer Immunotherapy clinical trials. She has spoken at symposia sponsored by Eli Lilly , Biogen , and Janssen and receives research support from Janssen Pharmaceuticals and Eli Lilly and Co. These relationships are not related to the content in the manuscript. R.A.S. also receives research support from the following grants: P01 AG036694, U01 AG032438, U01 AG024904, R01 AG037497, R01 AG034556, K24 AG035007, P50 AG005134, U19 AG010483, and R01 AG027435, Fidelity Biosciences , Harvard NeuroDiscovery Center , and the Alzheimer's Association.

FundersFunder number
Alzheimer's disease
Center for Functional Neuroimaging TechnologiesP41EB015896
Eli Lilly and Co.
ISIS Pharma
Janssen Alzheimer
Janssen Alzheimer's Immunotherapy
Janssen Immunotherapy
National Institutes of HealthR01 AG026484, U19 AG10483, K01 040197, R01 AG034556, P50 AG005134, P01 AG036694, K23 EB019023, R01 AG037497, R01EB014894, R21 AG038994, K23 AG049087, K24 AG035007, S10RR023043, R01 AG027435, R13 AG042201174210, S10RR021110, S10RR023401
U.S. Department of DefenseW81XWH-12-2-0012
National Institute on Aging
National Institute of Biomedical Imaging and Bioengineering
Alzheimer's AssociationZEN-10-174210
Harvard NeuroDiscovery Center
Eli Lilly and CompanyU01 AG032438, U19 AG010483
Johnson and Johnson
Janssen Research and Development
Massachusetts General Hospital
University of Southern California
Fidelity Biosciences
GE Healthcare
Alzheimer's Disease Neuroimaging InitiativeU01 AG024904
Janssen Pharmaceuticals
Northern California Institute for Research and Education
Fujirebio US
Canadian Institutes of Health Research
National Health and Medical Research CouncilAPP1105576
H. Lundbeck A/S


    • Alzheimer's disease
    • Amyloid
    • APOEε4
    • Subjective cognitive decline


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