Structural Neuroimaging of the Medial Temporal Lobe in Alzheimer’s Disease Clinical Trials

Article type: Review Article

Authors: Menéndez-González, Manuel^{a; b; c; *} | de Celis Alonso, Benito^{d; e} | Salas-Pacheco, José^f | Arias-Carrión, Oscar^{g; *}

Affiliations: [a] Unidad de Neurología, Hospital Álvarez-Buylla, Mieres, Asturias, España | [b] Departamento de Morfología y Biología Celular, Universidad de Oviedo, Oviedo, Asturias, España | [c] Instituto de Neurociencias, Universidad de Oviedo, Oviedo, Asturias, España | [d] Facultad de Ciencias Físico Matemáticas, Benemérita Universidad Autónoma de Puebla, Puebla, México | [e] Facultad para el Desarrollo, Carlos Sigüenza, Puebla, México | [f] Instituto de Investigación Científica, Universidad Juárez del Estado de Durango, Durango, México | [g] Unidad de Trastornos del Movimiento y Sueño (TMS), Hospital General Dr. Manuel Gea González/IFC-UNAM, México DF, México

Correspondence: [*] Correspondence to: Manuel Menéndez-González, Neurology Unit, Hospital Álvarez-Buylla, Murias s/n, 33616, Mieres, Spain. E-mail: [email protected]

Correspondence: [*] Correspondence to: Oscar Arias-Carrión, TMS Lab, Hospital General Dr. Manuel Gea González, Calzada de Tlalpan 4800, Mexico City 14080, Mexico. Tel.: +34 985 458 500; Fax: +34 985 458 406; [email protected]

Abstract: Atrophy in the medial temporal lobe (MTA) is being used as a criterion to support a diagnosis of Alzheimer’s disease (AD). There are several structural neuroimaging approaches for quantifying MTA, including semiquantitative visual rating scales, volumetry (3D), planimetry (2D), and linear measures (1D). Current applications of structural neuroimaging in Alzheimer’s disease clinical trials (ADCTs) incorporate it as a tool for improving the selection of subjects for enrollment or for stratification, for tracking disease progression, or providing evidence of target engagement for new therapeutic agents. It may also be used as a surrogate marker, providing evidence of disease-modifying effects. However, despite the widespread use of volumetric magnetic resonance imaging (MRI) in ADCTs, there are some important challenges and limitations, such as difficulties in the interpretation of results, limitations in translating results into clinical practice, and reproducibility issues, among others. Solutions to these issues may arise from other methodologies that are able to link the results of volumetric MRI from trials with conventional MRIs performed in routine clinical practice (linear or planimetric methods). Also of potential benefit are automated volumetry, using indices for comparing the relative rate of atrophy of different regions instead of absolute rates of atrophy, and combining structural neuroimaging with other biomarkers. In this review, authors present the existing structural neuroimaging approaches for MTA quantification. They then discuss solutions to the limitations of the different techniques as well as the current challenges of the field. Finally, they discuss how the current advances in AD neuroimaging can help AD diagnosis.

Keywords: Alzheimer’s disease, clinical trail, neuroimaging, structural

DOI: 10.3233/JAD-150226

Journal: Journal of Alzheimer's Disease, vol. 48, no. 3, pp. 581-589, 2015