title: Demyelination in mild cognitive impairment suggests progression path to Alzheimer's disease.
abstract: The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.
authors.affiliation: LREN, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne, Lausanne, Switzerland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Carmeli
authors.forename: Alessia
authors.initials: A
authors.lastname: Donati
authors.forename: Valérie
authors.initials: V
authors.lastname: Antille
authors.forename: Dragana
authors.initials: D
authors.lastname: Viceic
authors.forename: Joseph
authors.initials: J
authors.lastname: Ghika
authors.forename: Armin
authors.initials: A
authors.lastname: von Gunten
authors.forename: Stephanie
authors.initials: S
authors.lastname: Clarke
authors.forename: Reto
authors.initials: R
authors.lastname: Meuli
authors.forename: Richard S
authors.initials: RS
authors.lastname: Frackowiak
authors.forename: Maria G
authors.initials: MG
authors.lastname: Knyazeva
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D000647:Amnesia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications* / Q000503:physiopathology; D003710:Demography; D003711:Demyelinating Diseases / Q000150:complications* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D009929:Organ Size
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