Anterior cingulate sulcation is associated with onset and survival in frontotemporal dementia

Luke Harper, Sterre De Boer, Olof Lindberg, Jimmy Lätt, Nicholas Cullen, Lyles Clark, David Irwin, Lauren Massimo, Murray Grossman, Oskar Hansson, Yolande Pijnenburg, Corey T. McMillan, Alexander F. Santillo

Research output: Contribution to journalArticlepeer-review


Frontotemporal dementia is the second most common form of early onset dementia (<65 years). Despite this, there are few known disease-modifying factors. The anterior cingulate is a focal point of pathology in behavioural variant frontotemporal dementia. Sulcation of the anterior cingulate is denoted by the presence of a paracingulate sulcus, a tertiary sulcus developing, where present during the third gestational trimester and remaining stable throughout life. This study aims to examine the impact of right paracingulate sulcal presence on the expression and prognosis of behavioural variant frontotemporal dementia. This retrospective analysis drew its population from two clinical samples recruited from memory clinics at university hospitals in the USA and The Netherlands. Individuals with sporadic behavioural variant frontotemporal dementia were enrolled between 2000 and 2022 and followed up for an average of 7.71 years. T1-MRI data were evaluated for hemispheric paracingulate sulcal presence in accordance with an established protocol by two blinded raters. Outcome measures included age at onset, survival, cortical thickness and Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating determined clinical disease progression. The study population consisted of 186 individuals with sporadic behavioural variant frontotemporal dementia (113 males and 73 females), mean age 63.28 years (SD 8.32). The mean age at onset was 2.44 years later in individuals possessing a right paracingulate sulcus [60.2 years (8.54)] versus individuals who did not [57.76 (8.05)], 95% confidence interval > 0.41, P = 0.02. Education was not associated with age at onset (β = -0.05, P = 0.75). The presence of a right paracingulate sulcus was associated with an 83% increased risk of death per year after age at onset (hazard ratio 1.83, confidence interval [1.09-3.07], P < 0.02), whilst the mean age at death was similar for individuals with a present and absent right paracingulate sulcus (P = 0.7). Right paracingulate sulcal presence was not associated with baseline cortical thickness. Right paracingulate sulcal presence is associated with disease expression and survival in sporadic behavioural variant frontotemporal dementia. Findings provide evidence of neurodevelopmental brain reserve in behavioural variant frontotemporal dementia that may be important in the design of trials for future therapeutic approaches.

Original languageEnglish
Article numberfcad264
JournalBrain Communications
Issue number5
Publication statusPublished - 2023

Bibliographical note

Funding Information:
Work at the University of Pennsylvania was supported by National Institute of Health grants 5P01AG066597-03 6308 (C.T.M.), 5R01NS109260-04 (D.I.) and 1R01AG076832-01A1 (L.M.).

Funding Information:
Work at the Clinical Memory Research Unit Lund University was supported by the Swedish Research Council (2022-00775), the Knut and Alice Wallenberg foundation (2017-0383), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation (AF-980907), the Swedish Brain Foundation (FO2021-0293), The Parkinson foundation of Sweden (1412/22), the Cure Alzheimer’s fund, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Skåne University Hospital Foundation (2020-O000028), Regionalt Forskningsstöd (2022-1259) and the Swedish federal government under the Avtal om Läkarutbildning och Forskning (ALF) agreement (2022-Projekt0080). L.H., A.F.S. and O.L. are all supported by The Schörling foundation. A.F.S. and L.H. are funded primarily by the Swedish federal government under the Avtal om Läkarutbildning och Forskning (ALF) agreement (ALF YF 2023-2026/0017 and ALF ST 2021-2023/4-43338, respectively).

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.

Subject classification (UKÄ)

  • Neurosciences

Free keywords

  • brain reserve
  • cingulate
  • frontotemporal dementia
  • paracingulate
  • sulcation


Dive into the research topics of 'Anterior cingulate sulcation is associated with onset and survival in frontotemporal dementia'. Together they form a unique fingerprint.

Cite this