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Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers
Author(s) -
Chen Qin,
Boeve Bradley F.,
Tosakulwong Nirubol,
Lesnick Timothy,
Brushaber Danielle,
Dheel Christina,
Fields Julie,
Forsberg Leah,
Gavrilova Ralitza,
Gearhart Debra,
Haley Dana,
Gunter Jeffrey L.,
GraffRadford Jonathan,
Jones David,
Knopman David,
GraffRadford Neill,
Kraft Ruth,
Lapid Maria,
Rademakers Rosa,
Wszolek Zbigniew K.,
Rosen Howie,
Boxer Adam L.,
Kantarci Kejal
Publication year - 2019
Publication title -
journal of neuroimaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.822
H-Index - 64
eISSN - 1552-6569
pISSN - 1051-2284
DOI - 10.1111/jon.12642
Subject(s) - medicine , asymptomatic , asymptomatic carrier , pathology
BACKGROUND AND PURPOSE The objective of this study was to longitudinally investigate the trajectory of change in 1 H MRS measurements in asymptomatic MAPT mutation carriers who became symptomatic during follow‐up, and to determine the time at which the neurochemical alterations accelerated during disease progression. METHODS We identified eight MAPT mutations carriers who transitioned from asymptomatic to symptomatic disease during follow‐up. All participants were longitudinally followed with an average of 7.75 years (range 4‐11 years) and underwent two or more single voxel 1 H MRS examinations from the posterior cingulate voxel, with a total of 60 examinations. The rate of longitudinal change for each metabolite was estimated using linear mixed models. A flex point model was used to estimate the flex time point of the change in slope. RESULTS The decrease in the NAA/mI ratio accelerated 2.09 years prior to symptom onset, and continued to decline. A similar trajectory was observed in the presumed glial marker mI/Cr ratio accelerating 1.86 years prior to symptom onset. CONCLUSIONS Our findings support the potential use of longitudinal 1 H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.