4.6 Article

Cortical microstructure in primary progressive aphasia: a multicenter study

Journal

ALZHEIMERS RESEARCH & THERAPY
Volume 14, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13195-022-00974-0

Keywords

Diffusion; Magnetic resonance; Primary progressive aphasia; Alzheimer's disease; Frontotemporal lobar degeneration

Funding

  1. GBHI
  2. Alzheimer's Association
  3. Alzheimer's Society [GBHI ALZ UK-21-720973]
  4. Juan Rodes Contract from Instituto de Salud Carlos III [JR20/0018]
  5. PFIS contract from the Carlos III Health Institute [FI18/00275]
  6. Emili Letang post-residency research grant from Hospital Clinic de Barcelona
  7. NIH
  8. Miguel Servet I grant from the Carlos III Health Institute [CP20/00038]
  9. Spanish Ministry of Science, Innovation, and Universities
  10. Association for Frontotemporal Degeneration (Clinical Research Postdoctoral Fellowship, AFTD 2019-2021)
  11. FUNDELA
  12. Health Department of the Government of Catalonia [PERIS SLT002/16/00408]
  13. NIH [AG019724, AG032306, AG045390, NS092089, AG045333, AG056749, AG062422, P30AG062422, P01AG019724]
  14. National Institutes of Health (NIA) [1R01AG056850-01A1, R21AG056974, R01AG061566]
  15. Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III [PI14/01126, PI17/01019, PI13/01532, PI16/01825, PI18/00335, INT19/00016, PI18/00435, PI15/01618, PI20/00448, PI17/01896, PI20/01330, AC19:00103]
  16. CIBERNED program
  17. Fondo Europeo de Desarrollo Regional, Union Europea, una manera de hacer Europa
  18. Marato TV3 grant [20141210, 044412, 20143810]
  19. Generalitat de Catalunya [2014SGR-0235, PERIS SLT006/17/125, SLT006/17/00119]
  20. BBVA foundation
  21. Fundacio Bancaria La Caixa
  22. Sage Pharma [HCB2020/1483]

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Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in primary progressive aphasia (PPA). Increases in cortical mean diffusivity are correlated with cortical thinning and disease severity in PPA patients.
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.

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