Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation

NEUROBIOLOGY OF AGING

卷:55

Article

Wang, Jun Yi¹  Hessl, David^2,3  Hagerman, Randi J.^2,4  Simon, Tony J.^2,3  Tassone, Flora^2,5  Ferrer, Emilio⁶  Rivera, Susan M.^2,6 

[1] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA

[2] Univ Calif Davis, Med Ctr, Med Invest Neurodev Disorders MIND Inst, Sacramento, CA 95817 USA

[3] Univ Calif Davis, Sch Med, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA

[4] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA

[5] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Sacramento, CA 95817 USA

[6] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA

关键词: Fragile X;    FXTAS;    Fragile X premutation;    FMR1;    MRI;    Neurodegenerative disorder;   

DOI  :  10.1016/j.neurobiolaging.2017.03.018

来源: Elsevier

【 摘 要 】

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free