Alteration of regional homogeneity and white matter hyperintensities in amnestic mild cognitive impairment subtypes are related to cognition and CSF biomarkers
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Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Aβ level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.
KeywordsAlzheimer’s disease Cognition Mild cognitive impairment CSF White matter hyperintensities Magnetic resonance imaging Precuneus
This study was funded by the 12th Five-year Plan for National Science and Technology Supporting Program of China (Grant No. 2012BAI10B04), Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ14H180001 and Grant No. Y16H090026).
Data collection and sharing for this project was funded by the Alzheimer”s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.;Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; ElanPharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliatedcompany Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen AlzheimerImmunotherapy Research & Development, LLC.; Johnson & Johnson PharmaceuticalResearch & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; MesoScaleDiagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis PharmaceuticalsCorporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; andTransition Therapeutics. The Canadian Institutes of Health Research is providing funds tosupport ADNI clinical sites in Canada. Private sector contributions are facilitated by theFoundation for the National Institutes of Health (www.fnih.org). The grantee organization isthe Northern California Institute for Research and Education, and the study is coordinatedby the Alzheimer”s Disease Cooperative Study at the University of California, San Diego.ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Compliance with ethical standards
This study was funded by National Key Research and Development Program of China (No. 2016YFC1306600), Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ14H180001 and Grant No. Y16H090026).
Conflict of interest
The authors declare that they have no conflict of interest.
“All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”
Written informed consent was obtained from all participants and/or authorized representatives and the study partners before any protocol-specific procedures were carried out in the ADNI study.
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