Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion

Janne M. Papma, Lize C. Jiskoot, Jessica L. Panman, Elise G. Dopper, Tom Den Heijer, Laura Donker Kaat, Yolande A.L. Pijnenburg, Lieke H. Meeter, Rick Van Minkelen, Serge A.R.B. Rombouts, John C. Van Swieten

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). Methods: Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. Results: Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. Conclusions: This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.

Original languageEnglish
Pages (from-to)1256-1264
Number of pages9
JournalNeurology
Volume89
Issue number12
DOIs
Publication statusPublished - 19 Sep 2017

Cite this

Papma, J. M., Jiskoot, L. C., Panman, J. L., Dopper, E. G., Den Heijer, T., Donker Kaat, L., ... Van Swieten, J. C. (2017). Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology, 89(12), 1256-1264. https://doi.org/10.1212/WNL.0000000000004393
Papma, Janne M. ; Jiskoot, Lize C. ; Panman, Jessica L. ; Dopper, Elise G. ; Den Heijer, Tom ; Donker Kaat, Laura ; Pijnenburg, Yolande A.L. ; Meeter, Lieke H. ; Van Minkelen, Rick ; Rombouts, Serge A.R.B. ; Van Swieten, John C. / Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. In: Neurology. 2017 ; Vol. 89, No. 12. pp. 1256-1264.
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title = "Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion",
abstract = "Objective: To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). Methods: Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. Results: Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. Conclusions: This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.",
author = "Papma, {Janne M.} and Jiskoot, {Lize C.} and Panman, {Jessica L.} and Dopper, {Elise G.} and {Den Heijer}, Tom and {Donker Kaat}, Laura and Pijnenburg, {Yolande A.L.} and Meeter, {Lieke H.} and {Van Minkelen}, Rick and Rombouts, {Serge A.R.B.} and {Van Swieten}, {John C.}",
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Papma, JM, Jiskoot, LC, Panman, JL, Dopper, EG, Den Heijer, T, Donker Kaat, L, Pijnenburg, YAL, Meeter, LH, Van Minkelen, R, Rombouts, SARB & Van Swieten, JC 2017, 'Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion' Neurology, vol. 89, no. 12, pp. 1256-1264. https://doi.org/10.1212/WNL.0000000000004393

Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. / Papma, Janne M.; Jiskoot, Lize C.; Panman, Jessica L.; Dopper, Elise G.; Den Heijer, Tom; Donker Kaat, Laura; Pijnenburg, Yolande A.L.; Meeter, Lieke H.; Van Minkelen, Rick; Rombouts, Serge A.R.B.; Van Swieten, John C.

In: Neurology, Vol. 89, No. 12, 19.09.2017, p. 1256-1264.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion

AU - Papma, Janne M.

AU - Jiskoot, Lize C.

AU - Panman, Jessica L.

AU - Dopper, Elise G.

AU - Den Heijer, Tom

AU - Donker Kaat, Laura

AU - Pijnenburg, Yolande A.L.

AU - Meeter, Lieke H.

AU - Van Minkelen, Rick

AU - Rombouts, Serge A.R.B.

AU - Van Swieten, John C.

PY - 2017/9/19

Y1 - 2017/9/19

N2 - Objective: To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). Methods: Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. Results: Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. Conclusions: This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.

AB - Objective: To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). Methods: Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. Results: Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. Conclusions: This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.

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Papma JM, Jiskoot LC, Panman JL, Dopper EG, Den Heijer T, Donker Kaat L et al. Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology. 2017 Sep 19;89(12):1256-1264. https://doi.org/10.1212/WNL.0000000000004393