Age-dependent cognitive changes in carriers of the fragile X syndrome

Kim M. Cornish, Lexin Li, Cary S. Kogan, Sebastien Jacquemont, Jeremy Turk, Ann Dalton, Randi J Hagerman, Paul J Hagerman

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Fragile X syndrome is a neurodevelopmental disorder that is caused by the silencing of a single gene on the X chromosome, the fragile X mental retardation 1 (FMR1) gene. Affected individuals display a unique neurocognitive phenotype that includes significant impairment in inhibitory control, selective attention, working memory, and visual-spatial cognition. In contrast, little is known about the trajectory and specificity of any cognitive impairment associated with the fragile X premutation (i.e., "carrier status") or its relationship with the recently identified neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). In the present study, we evaluated a broad sample of 40 premutation males (PM) aged 18-69 years matched on age and IQ to 67 unaffected comparison males (NC). Performance was compared across a range of cognitive domains known to be impaired in fragile X syndrome (i.e., "full mutation"). Tremor was also assessed using a self-report neurological questionnaire. PM displayed statistically significant deficits in their ability to inhibit prepotent responses, differentiating them from NC from age 30 onwards. With increasing age, the two groups follow different trajectories, with PM developing progressively more severe problems in inhibitory control. This deficit also has a strong co-occurrence in males displaying FXTAS-related symptomatology (p < .001). Selective attention was also impaired in PM but did not show any disproportionate aging effect. No other cognitive deficits were observed. We conclude that an inhibitory deficit and its impact across the lifespan are specifically associated with the fragile X premutation status, and may be a precursor for development of a more severe form of cognitive impairment or dementia, which has been reported in patients with the diagnosis of FXTAS.

Original languageEnglish (US)
Pages (from-to)628-636
Number of pages9
JournalCortex
Volume44
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Fragile X Syndrome
X-Linked Genes
Aptitude
Tremor
Short-Term Memory
Intellectual Disability
Neurodegenerative Diseases
Self Report
Cognition
Dementia
Phenotype
Mutation
Genes
Fragile X Tremor Ataxia Syndrome

Keywords

  • Attention
  • Cognition
  • Fragile X permutation
  • Fragile X syndrome
  • Fragile X-associated tremor/ataxia syndrome (FXTAS)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Cornish, K. M., Li, L., Kogan, C. S., Jacquemont, S., Turk, J., Dalton, A., ... Hagerman, P. J. (2008). Age-dependent cognitive changes in carriers of the fragile X syndrome. Cortex, 44(6), 628-636. https://doi.org/10.1016/j.cortex.2006.11.002

Age-dependent cognitive changes in carriers of the fragile X syndrome. / Cornish, Kim M.; Li, Lexin; Kogan, Cary S.; Jacquemont, Sebastien; Turk, Jeremy; Dalton, Ann; Hagerman, Randi J; Hagerman, Paul J.

In: Cortex, Vol. 44, No. 6, 06.2008, p. 628-636.

Research output: Contribution to journalArticle

Cornish, KM, Li, L, Kogan, CS, Jacquemont, S, Turk, J, Dalton, A, Hagerman, RJ & Hagerman, PJ 2008, 'Age-dependent cognitive changes in carriers of the fragile X syndrome', Cortex, vol. 44, no. 6, pp. 628-636. https://doi.org/10.1016/j.cortex.2006.11.002
Cornish KM, Li L, Kogan CS, Jacquemont S, Turk J, Dalton A et al. Age-dependent cognitive changes in carriers of the fragile X syndrome. Cortex. 2008 Jun;44(6):628-636. https://doi.org/10.1016/j.cortex.2006.11.002
Cornish, Kim M. ; Li, Lexin ; Kogan, Cary S. ; Jacquemont, Sebastien ; Turk, Jeremy ; Dalton, Ann ; Hagerman, Randi J ; Hagerman, Paul J. / Age-dependent cognitive changes in carriers of the fragile X syndrome. In: Cortex. 2008 ; Vol. 44, No. 6. pp. 628-636.
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