Structural Brain Changes in Pre-Clinical FTD MAPT Mutation Carriers

Article type: Research Article

Authors: Domínguez-Vivero, Clara^{a; *} | Wu, Liwen^b | Lee, Seonjoo^b | Manoochehri, Masood^a | Cines, Sarah^{a; f} | Brickman, Adam M.^a | Rizvi, Batool^a | Chesebro, Anthony^a | Gazes, Yunglin^a | Fallon, Emer^d | Lynch, Timothy^d | Heidebrink, Judith L.^e | Paulson, Henry^e | Goldman, Jill S.^a | Huey, Edward^{a; c} | Cosentino, Stephanie^a

Affiliations: [a] Department of Neurology, Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, New York, NY, USA | [b] Department of Biostatistics, Columbia University, Mailman School of Public Health, New York, NY, USA | [c] Department of Psychiatry & New York State Psychiatric Institute, Columbia University, New York, NY, USA | [d] Dublin Neurological Institute, Dublin, Ireland | [e] Department of Neurology, The University of Michigan, Ann Arbor, MI, USA | [f] Fairleigh Dickinson University, Teaneck, NJ, USA

Correspondence: [*] Correspondence to: Clara Dominguez, MD, 630 West 168th Street, P&S Box 16, New York, NY 10032, USA. Tel.: +1 212 305 1134; E-mail: [email protected].

Abstract: Background:Frontotemporal dementia (FTD) is the second most common cause of early-onset neurodegenerative dementia. Several studies have focused on early imaging changes in FTD patients, but once subjects meet full criteria for FTD diagnosis, structural changes are generally widespread. Objective:This study aims to determine the earliest structural brain changes in asymptomatic MAPT MUTATION carriers. Methods:This is a cross-sectional multicenter study comparing global and regional brain volume and white matter integrity in a group of MAPT mutation preclinical carriers and controls. Participants belong to multiple generations of six families with five MAPT mutations. All participants underwent a medical examination, neuropsychological tests, genetic analysis, and a magnetic resonance scan (3T, scout, T1-weighted image followed by EPI (BOLD), MPRAGE, DTI, FLAIR, and ASL sequences). Results:Volumes of five cortical and subcortical areas were strongly correlated with mutation status: temporal lobe (left amygdala, left temporal pole), cingulate cortex (left rostral anterior cingulate gyrus, right posterior cingulate), and the lingual gyrus in the occipital lobe. We did not find significant differences in whole brain volume, white matter hyperintensities volume, and white matter integrity using DTI analysis. Conclusion:Temporal lobe, cingulate cortex and the lingual gyrus seem to be early targets of the disease and may serve as biomarkers for FTD prior to overt symptom onset.

Keywords: Atrophy, brain atrophy, early detection, frontotemporal lobar degeneration, MAPT mutation

DOI: 10.3233/JAD-190820

Journal: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 595-606, 2020