title: The Disconnection Hypothesis in Alzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging.
abstract: According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p <  0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.
authors.affiliation: Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Lacalle-Aurioles
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Navas-Sánchez
authors.affiliation: Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Alemán-Gómez
authors.affiliation: Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Olazarán
authors.affiliation: Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan Adán
authors.initials: JA
authors.lastname: Guzmán-De-Villoria
authors.affiliation: Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cruz-Orduña
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Mateos-Pérez
authors.affiliation: Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D002533:Cerebral Angiography / Q000379:methods; D002560:Cerebrovascular Circulation / Q000502:physiology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008609:Mental Status Schedule; D008959:Models, Neurological; D064847:Multimodal Imaging / Q000379:methods*; D009929:Organ Size; D011446:Prospective Studies
keywords: Alzheimer’s disease; diffusion tensor imaging; disconnection hypothesis; magnetic resonance imaging; mild cognitive impairment; perfusion weighted imaging