Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Maurice Pasternak, Saira S. Mirza, Nicholas Luciw, on behalf of the Genetic Frontotemporal dementia Initiative (GENFI), Henri J.M.M. Mutsaerts, Jan Petr, David L. Thomas, David Cash, Martina Bocchetta, Maria Carmela Tartaglia, Sara B. Mitchell, Sandra E. Black, Morris Freedman, David Tang-Wai, Ekaterina Rogaeva, Lucy L. Russell, Arabella Bouzigues, John C. van Swieten, Lize C. Jiskoot, Harro SeelaarRobert Laforce, Pietro Tiraboschi, Barbara Borroni, Daniela Galimberti, James B. Rowe, Caroline Graff, Elizabeth Finger, Sandro Sorbi, Alexandre de Mendonça, Chris Butler, Alex Gerhard, Raquel Sanchez-Valle, Fermin Moreno, Matthis Synofzik, Rik Vandenberghe, Simon Ducharme, Johannes Levin, Markus Otto, Isabel Santana, Antonio P. Strafella, Bradley J. MacIntosh, Jonathan D. Rohrer, Mario Masellis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


INTRODUCTION: Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. METHODS: We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. RESULTS: Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset. DISCUSSION: Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. Highlights: Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups. Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Original languageEnglish
Pages (from-to)3525-3542
Number of pages18
JournalAlzheimer's and Dementia
Issue number5
Publication statusPublished - May 2024

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