Elizabeth C Mormino1, Kathryn V Papp2, Dorene M Rentz2, Michael C Donohue3, Rebecca Amariglio2, Yakeel T Quiroz4, Jasmeer Chhatwal1, Gad A Marshall2, Nancy Donovan5, Jonathan Jackson1, Jennifer R Gatchel5, Bernard J Hanseeuw1, Aaron P Schultz6, Paul S Aisen3, Keith A Johnson7, Reisa A Sperling8. 1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3. Department of Neurology, Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA. 4. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 5. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 6. Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 7. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 8. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: reisa@rics.bwh.harvard.edu.
Abstract
INTRODUCTION: Sensitive detection of cognitive decline over the course of preclinical Alzheimer's disease is critical as the field moves toward secondary prevention trials. METHODS: We examined amyloid β (Aβ)-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer's Disease Cooperative Study Prevention Instrument Study as a replication cohort. RESULTS: Aβ+ CN individuals demonstrated longitudinal decline on all individual PACC components and all PACC variations. Aβ group differences emerged earlier when Free and Cued Selective Reminding Test Free Recall was included in the PACC. PACC decline was associated with Clinical Dementia Rating progression. DISCUSSION: This independent data set and a replication cohort confirm the ability of the PACC to capture both early and late cognitive decline during the preclinical stages of Alzheimer's disease, which may prove advantageous in the prevention trial design.
INTRODUCTION: Sensitive detection of cognitive decline over the course of preclinical Alzheimer's disease is critical as the field moves toward secondary prevention trials. METHODS: We examined amyloid β (Aβ)-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer's Disease Cooperative Study Prevention Instrument Study as a replication cohort. RESULTS: Aβ+ CN individuals demonstrated longitudinal decline on all individual PACC components and all PACC variations. Aβ group differences emerged earlier when Free and Cued Selective Reminding Test Free Recall was included in the PACC. PACC decline was associated with Clinical Dementia Rating progression. DISCUSSION: This independent data set and a replication cohort confirm the ability of the PACC to capture both early and late cognitive decline during the preclinical stages of Alzheimer's disease, which may prove advantageous in the prevention trial design.
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