Cortical microstructure in primary progressive aphasia: a multicenter study

Alzheimer's research & therapy

Alzheimers Res Ther. 2022 Feb 9;14(1):27. doi: 10.1186/s13195-022-00974-0.


BACKGROUND: Cortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).

METHODS: In this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.

RESULTS: The comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.

CONCLUSIONS: Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.

PMID:35139897 | PMC:PMC8830043 | DOI:10.1186/s13195-022-00974-0


Ignacio Illán-Gala
Victor Montal
Sergi Borrego-Écija
Maria Luisa Mandelli
Neus Falgàs
Ariane E Welch
Jordi Pegueroles
Miguel Santos-Santos
Alexandre Bejanin
Daniel Alcolea
Oriol Dols-Icardo
Olivia Belbin
Mª Belén Sánchez-Saudinós
Nuria Bargalló
Sofía González-Ortiz
Albert Lladó
Rafael Blesa
Bradford C Dickerson
Howard J Rosen
Bruce L Miller
Alberto Lleó
Maria Luisa Gorno-Tempini
Raquel Sánchez-Valle
Juan Fortea