期刊
ALZHEIMERS RESEARCH & THERAPY
卷 8, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13195-016-0220-z
关键词
Prognosis; Alzheimer's disease; Mild cognitive impairment; Cerebrospinal fluid
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- 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
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
Background: According to new diagnostic guidelines for Alzheimer's disease (AD), biomarkers enable estimation of the individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementia for patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affect the progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF) biomarker constellations on the progression risk of MCI patients. Methods: A multicentre cohort of 469 patients with MCI and available CSF biomarker results and clinical follow-up data was considered. Biomarker values were categorized as positive for AD, negative or borderline. Progression risk differences between patients with different constellations of total Tau (t-Tau), phosphorylated Tau at threonine 181 (p-Tau) and amyloid-beta 1-42 (A beta(42)) were studied. Group comparison analyses and Cox regression models were employed. Results: Patients with all biomarkers positive for AD (N = 145) had the highest hazard for progression to dementia due to AD, whilst patients with no positive biomarkers (N = 111) had the lowest. The risk of patients with only abnormal p-Tau and/or t-Tau (N = 49) or with positive A beta(42) in combination with positive t-Tau or p-Tau (N = 119) is significantly lower than that of patients with all biomarkers positive. Conclusions: The risk of progression to dementia due to AD differs between patients with different CSF biomarker constellations.
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