Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease
- 21 August 2014
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 11 (5), 511-522
- https://doi.org/10.1016/j.jalz.2014.05.1754
Abstract
Background We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD). Methods We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1–42 (Aβ1–42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132). Results CSF Aβ1–42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage. Conclusion This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.Keywords
Funding Information
- Alzheimer's Disease Neuroimaging Initiative
- National Institutes of Health (U01 AG024904)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Abbott Laboratories
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Amorfix Life Sciences
- AstraZeneca
- Bayer HealthCare
- BioClinica
- Bristol-Myers Squibb
- Eli Lilly and Company
- Roche
- Genentech
- GE Healthcare
- Merck
- Meso Scale Diagnostics
- Novartis Pharmaceuticals Corporation
- Pfizer
- Servier
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
- National Institutes of Health (P30 AG010129, K01 AG030514)
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