Journal
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
Volume 12, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/dad2.12068
Keywords
ADNI-1; Alzheimer's disease; anterolateral entorhinal cortex; biomarker; brain imaging; Clinical Dementia Rating; cortical thickness; cerebrospinal fluid amyloid; linear mixed-effects models; memory; mild cognitive impairment; Mini-Mental State Exam; posteromedial entorhinal cortex; receiver operating characteristic
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Funding
- NSF [DGE-1321846, B2D-1612490]
- NIA [R01AG053555, P50AG05146]
- Alzheimer's Disease Neuroimaging Initiative (ADNI
- National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Com- pany
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC
- Northern California Institute for Research and Education
- [T32 AG000096]
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IntroductionLoss of entorhinal cortex (EC) layer II neurons represents the earliest Alzheimer's disease (AD) lesion in the brain. Research suggests differing functional roles between two EC subregions, the anterolateral EC (aLEC) and the posteromedial EC (pMEC). MethodsWe use joint label fusion to obtain aLEC and pMEC cortical thickness measurements from serial magnetic resonance imaging scans of 775 ADNI-1 participants (219 healthy; 380 mild cognitive impairment; 176 AD) and use linear mixed-effects models to analyze longitudinal associations among cortical thickness, disease status, and cognitive measures. ResultsGroup status is reliably predicted by aLEC thickness, which also exhibits greater associations with cognitive outcomes than does pMEC thickness. Change in aLEC thickness is also associated with cerebrospinal fluid amyloid and tau levels. DiscussionThinning of aLEC is a sensitive structural biomarker that changes over short durations in the course of AD and tracks disease severity-it is a strong candidate biomarker for detection of early AD.
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