Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22166
Title: Clinical meaningfulness of subtle cognitive decline on longitudinal testing in preclinical AD.
Austin Authors: Papp, Kathryn V;Buckley, Rachel;Mormino, Elizabeth;Maruff, Paul;Villemagne, Victor L ;Masters, Colin L ;Johnson, Keith A;Rentz, Dorene M;Sperling, Reisa A;Amariglio, Rebecca E
Affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
CogState, Ltd, Melbourne, Victoria, Australia
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
Issue Date: Mar-2020
metadata.dc.date: 2020-01-04
Publication information: Alzheimer's & Dementia 2020; 16(3): 552-560
Abstract: Demonstrating the "clinical meaningfulness" of slowing early cognitive decline in clinically normal (CN) older adults with elevated amyloid-β (Aβ+) is critical for Alzheimer's disease secondary prevention trials and for understanding early cognitive progression. Cox regression analyses were used to determine whether 3-year slopes on the preclinical Alzheimer's cognitive composite predicted MCI diagnosis and global Clinical Dementia Rating>0 in 267 Aβ+ CN individuals participating in the Harvard Aging Brain Study, Australian Imaging, Biomarker and Lifestyle Study, and Alzheimer's Disease Neuroimaging Initiative. Steeper preclinical Alzheimer's cognitive composite decline over 3 years was associated with increased risk for MCI diagnosis and global Clinical Dementia Rating>0 in the following years across all cohorts. Hazard ratios using meta-analytic estimates were 5.47 (95% CI: 3.25-9.18) for MCI diagnosis and 4.49 (95% CI: 2.84-7.09) for Clinical Dementia Rating>0 in those with subtle decline (>-.14 to -.26 preclinical Alzheimer's cognitive composite standard deviations/year) on longitudinal cognitive testing. Early "subtle cognitive decline" among Aβ+ CN on a sensitive cognitive composite demonstrably increases risk for imminent clinical disease progression and functional impairment.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22166
DOI: 10.1016/j.jalz.2019.09.074
ORCID: 0000-0002-5832-9875
PubMed URL: 31759879
Type: Journal Article
Subjects: Alzheimer's disease
Amyloid
Clinical meaningfulness
Clinical trials methodology
Outcome research
Preclinical
Secondary prevention
Appears in Collections:Journal articles

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