The Disconnection Hypothesis in Alzheimer’s Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging

Article type: Research Article

Authors: Lacalle-Aurioles, María^{a; b; c; 1} | Navas-Sánchez, Francisco Javier^{b; c} | Alemán-Gómez, Yasser^{a; b; c} | Olazarán, Javier^d | Guzmán-De-Villoria, Juan Adán^e | Cruz-Orduña, Isabel^d | Mateos-Pérez, José María^{c; b} | Desco, Manuel^{a; b; c; *}

Affiliations: [a] Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain | [b] Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain | [c] Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain | [d] Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain | [e] Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain

Correspondence: [*] Correspondence to: Manuel Desco, Unidad de Medicina y Cirugía Experimental, Hospital General Universitario Gregorio Marañón, C/Dr. Esquerdo, 46, 28007 Madrid, Spain. Tel.: +34 914265047; Fax: +34 914265108; E-mail: [email protected].

Note: [1] Present address: Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, Montréal,Quebec, Canada.

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.

Keywords: Alzheimer’s disease, diffusion tensor imaging, disconnection hypothesis, magnetic resonance imaging, mild cognitive impairment, perfusion weighted imaging

DOI: 10.3233/JAD-150288

Journal: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 1051-1064, 2016