Journal
NEUROLOGY
Volume 91, Issue 15, Pages E1402-E1412Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000006310
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Funding
- NIH [P01AG007232, R01AG037212, RF1AG054023, R01AG034189, R56AG034189]
- National Center for Advancing Translational Sciences, NIH [UL1TR001873]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [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
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- Fujirebio
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Merck Co., Inc.
- Meso Scale Diagnostics
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
- AbbVie
- BioClinica, Inc.
- Eisai Inc.
- F. Hoffmann-La Roche Ltd.
- Genentech, Inc.
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Lumosity
- Lundbeck
- Meso Scale Diagnostics, LLC.
- Neurotrack Technologies
- Piramal Imaging
- Servier
- Transition Therapeutics
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Objective To develop, replicate, and validate an MRI-based quantitative measure of both cerebrovascular and neurodegeneration in Alzheimer disease (AD) for clinical and potentially research purposes. Methods We used data from a cross-sectional and longitudinal community-based study of Medicare-eligible residents in northern Manhattan followed every 18-24 months (n = 1,175, mean age 78 years). White matter hyperintensities, infarcts, hippocampal volumes, and cortical thicknesses were quantified from MRI and combined to generate an MRI measure associated with episodic memory. The combined MRI measure was replicated and validated using autopsy data, clinical diagnoses, and CSF biomarkers and amyloid PET from the Alzheimer's Disease Neuroimaging Initiative. Results The quantitative MRI measure was developed in a group of community participants (n = 690) and replicated in a similar second group (n = 485). Compared with healthy controls, the quantitative MRI measure was lower in patients with mild cognitive impairment and lower still in those with clinically diagnosed AD. The quantitative MRI measure correlated with neurofibrillary tangles, neuronal loss, atrophy, and infarcts at postmortem in an autopsy subset and was also associated with PET amyloid imaging and CSF levels of total tau, phosphorylated tau, and beta-amyloid 42. The MRI measure predicted conversion to MCI and clinical AD among healthy controls. Conclusion We developed, replicated, and validated an MRI measure of cerebrovascular and neurodegenerative pathologies that are associated with clinical and neuropathologic diagnosis of AD and related to established biomarkers.
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