Inferior Frontal Sulcal Hyperintensities on Brain MRI Are Associated with Amyloid Positivity beyond Age—Results from the Multicentre Observational DELCODE Study

Marc Dörner, Katharina Seebach, Michael T. Heneka, Inga Menze, Roland von Känel, Sebastian Euler, Frank Schreiber, Philipp Arndt, Katja Neumann, Annkatrin Hildebrand, Anna Charlotte John, Anthony Tyndall, Johannes Kirchebner, Pawel Tacik, Robin Jansen, Alexander Grimm, Solveig Henneicke, Valentina Perosa, Sven G. Meuth, Oliver PetersJulian Hellmann-Regen, Lukas Preis, Josef Priller, Eike Jakob Spruth, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Frank Jessen, Ayda Rostamzadeh, Wenzel Glanz, Jan Ben Schulze, Sarah Lavinia Florence Schiebler, Katharina Buerger, Daniel Janowitz, Robert Perneczky, Boris Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Christoph Laske, Matthias H. Munk, Annika Spottke, Nina Roy-Kluth, Michael Wagner, Ingo Frommann, Falk Lüsebrink, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Luca Kleineidam, Melina Stark, Matthias Schmid, Ersin Ersözlü, Frederic Brosseron, Michael Ewers, Björn H. Schott, Emrah Düzel, Gabriel Ziegler, Hendrik Mattern, Stefanie Schreiber, Jose Bernal

Research output: Contribution to journalArticlepeer-review


Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer’s disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aβ42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05–3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57–2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00–1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26–0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid β beyond age.

Original languageEnglish
Article number940
Issue number9
StatePublished - May 2024
Externally publishedYes


  • Alzheimer’s disease
  • amyloid positivity
  • fluid-attenuated inversion recovery
  • glymphatic system
  • inferior frontal sulcal hyperintensity
  • magnetic resonance imaging


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