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Alzheimers Dement. 2019 Sep 7. pii: S1552-5260(19)35122-2. doi: 10.1016/j.jalz.2019.06.4955. [Epub ahead of print]

A harmonized longitudinal biomarkers and cognition database for assessing the natural history of preclinical Alzheimer's disease from young adulthood and for designing prevention trials.

Author information

1
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: chengjie@wustl.edu.
2
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center Biostatistics Core Washington University School of Medicine, St. Louis, MO, USA.
3
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
4
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6
Wisconsin Alzheimer's Institute and Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S Middleton Veterans Memorial Hospital, Madison, WI, USA.
7
Wisconsin Alzheimer's Institute and Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
8
The Florey Institute, University of Melbourne, Melbourne, Australia.
9
Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia.
10
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
11
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
12
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
13
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Departments of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Abstract

INTRODUCTION:

Large longitudinal biomarkers database focusing on middle age is needed for Alzheimer's disease (AD) prevention.

METHODS:

Data for cerebrospinal fluid analytes, molecular imaging of cerebral fibrillar β-amyloid with positron emission tomography, magnetic resonance imaging-based brain structures, and clinical/cognitive outcomes were harmonized across eight AD biomarker studies. Statistical power was estimated.

RESULTS:

The harmonized database included 7779 participants with clinical/cognitive data: 3542 were 18∼65 years at the baseline, 5865 had longitudinal cognitive data for a median of 4.7 years, 2473 participated in the cerebrospinal fluid studies (906 had longitudinal data), 2496 participated in the magnetic resonance imaging studies (1283 had longitudinal data), and 1498 participated in the positron emission tomography amyloid studies (849 had longitudinal data). The database provides adequate power for detecting early biomarker changes, and demonstrates the feasibility of AD prevention trials on middle-aged individuals.

DISCUSSION:

The harmonized database is an optimum resource to design AD prevention trials decades before symptomatic onset.

KEYWORDS:

Alzheimer disease; Amyloid imaging with positron emission tomography (PET) using the [(11)C] benzothiazole tracer; Biomarkers; Cerebrospinal fluid (CSF); Magnetic resonance imaging (MRI) volumetrics; Pittsburgh Compound-B (PIB); Preclinical stages; Prevention trials

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