Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers

Qin Chen, Bradley F Boeve, Nirubol Tosakulwong, Timothy Lesnick, Danielle Brushaber, Christina Dheel, Julie A Fields, Leah Forsberg, Ralitza M Gavrilova, Debra Gearhart, Dana Haley, Jeffrey L. Gunter, Jonathan Graff-Radford, David T Jones, David S Knopman, Neill R Graff Radford, Ruth Kraft, Maria Isabel Lapid, Rosa V Rademakers, Zbigniew K Wszolek & 3 others Howie Rosen, Adam L. Boxer, Kejal M Kantarci

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND PURPOSE: The objective of this study was to longitudinally investigate the trajectory of change in 1H 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 1H 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 1H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.

Original languageEnglish (US)
JournalJournal of Neuroimaging
DOIs
StatePublished - Jan 1 2019

Fingerprint

Frontotemporal Lobar Degeneration
Magnetic Resonance Spectroscopy
Mutation
Brain
Gyrus Cinguli
Neuroglia
Disease Progression
Linear Models
Proton Magnetic Resonance Spectroscopy

Keywords

  • converter
  • frontotemporal lobar degeneration
  • longitudinal
  • MAPT
  • MRS

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology

Cite this

Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers. / Chen, Qin; Boeve, Bradley F; Tosakulwong, Nirubol; Lesnick, Timothy; Brushaber, Danielle; Dheel, Christina; Fields, Julie A; Forsberg, Leah; Gavrilova, Ralitza M; Gearhart, Debra; Haley, Dana; Gunter, Jeffrey L.; Graff-Radford, Jonathan; Jones, David T; Knopman, David S; Graff Radford, Neill R; Kraft, Ruth; Lapid, Maria Isabel; Rademakers, Rosa V; Wszolek, Zbigniew K; Rosen, Howie; Boxer, Adam L.; Kantarci, Kejal M.

In: Journal of Neuroimaging, 01.01.2019.

Research output: Contribution to journalArticle

@article{194cbccea6014205bab456e98dd4143e,
title = "Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers",
abstract = "BACKGROUND AND PURPOSE: The objective of this study was to longitudinally investigate the trajectory of change in 1H 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 1H 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 1H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.",
keywords = "converter, frontotemporal lobar degeneration, longitudinal, MAPT, MRS",
author = "Qin Chen and Boeve, {Bradley F} and Nirubol Tosakulwong and Timothy Lesnick and Danielle Brushaber and Christina Dheel and Fields, {Julie A} and Leah Forsberg and Gavrilova, {Ralitza M} and Debra Gearhart and Dana Haley and Gunter, {Jeffrey L.} and Jonathan Graff-Radford and Jones, {David T} and Knopman, {David S} and {Graff Radford}, {Neill R} and Ruth Kraft and Lapid, {Maria Isabel} and Rademakers, {Rosa V} and Wszolek, {Zbigniew K} and Howie Rosen and Boxer, {Adam L.} and Kantarci, {Kejal M}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/jon.12642",
language = "English (US)",
journal = "Journal of Neuroimaging",
issn = "1051-2284",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers

AU - Chen, Qin

AU - Boeve, Bradley F

AU - Tosakulwong, Nirubol

AU - Lesnick, Timothy

AU - Brushaber, Danielle

AU - Dheel, Christina

AU - Fields, Julie A

AU - Forsberg, Leah

AU - Gavrilova, Ralitza M

AU - Gearhart, Debra

AU - Haley, Dana

AU - Gunter, Jeffrey L.

AU - Graff-Radford, Jonathan

AU - Jones, David T

AU - Knopman, David S

AU - Graff Radford, Neill R

AU - Kraft, Ruth

AU - Lapid, Maria Isabel

AU - Rademakers, Rosa V

AU - Wszolek, Zbigniew K

AU - Rosen, Howie

AU - Boxer, Adam L.

AU - Kantarci, Kejal M

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND AND PURPOSE: The objective of this study was to longitudinally investigate the trajectory of change in 1H 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 1H 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 1H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.

AB - BACKGROUND AND PURPOSE: The objective of this study was to longitudinally investigate the trajectory of change in 1H 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 1H 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 1H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.

KW - converter

KW - frontotemporal lobar degeneration

KW - longitudinal

KW - MAPT

KW - MRS

UR - http://www.scopus.com/inward/record.url?scp=85067660845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067660845&partnerID=8YFLogxK

U2 - 10.1111/jon.12642

DO - 10.1111/jon.12642

M3 - Article

JO - Journal of Neuroimaging

JF - Journal of Neuroimaging

SN - 1051-2284

ER -