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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.
GLOSSARY
- ALS=
- amyotrophic lateral sclerosis;
- AxD=
- axial diffusivity;
- BDI=
- Beck Depression Inventory;
- bvFTD=
- behavioral variant frontotemporal dementia;
- C9orf72RE=
- chromosome 9 open reading frame 72 repeat expansion;
- CBI-R=
- Cambridge Behavioural Inventory–Revised;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- FAB=
- Frontal Assessment Battery;
- FTD=
- frontotemporal dementia;
- FWE=
- family-wise error;
- HC=
- healthy control;
- MD=
- mean diffusivity;
- MMSE=
- Mini-Mental State Examination;
- NPI=
- Neuropsychiatric Inventory;
- RD=
- radial diffusivity;
- TBSS=
- tract-based spatial statistics;
- TMT=
- Trail Making Test;
- VBM=
- voxel-based morphometry;
- WAIS=
- Wechsler Adult Intelligence Scale
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received March 13, 2017.
- Accepted in final form June 29, 2017.
- © 2017 American Academy of Neurology
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