Cognitive and motor functioning in elderly glucocerebrosidase mutation carriers.

Abstract

Mutations in the glucocerebrosidase (GBA) gene are a strong genetic risk factor for the development of Parkinson's disease and dementia with Lewy Bodies. However the penetrance of GBA mutations is low for these diseases in heterozygous carriers. The aim of this study was to examine the relationship between mutation status and cognitive and motor functioning in a sample of community-dwelling older adults. Using linear mixed effects models, we examined the effect of heterozygous mutation status on 736 community-dwelling older adults (≥70 years) without dementia or Parkinson's disease assessed over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S). Verbal memory was measured using the picture version of the Free and Cued Selective Reminding Test, and carriers showed significantly (p < 0.05) greater decline in verbal memory over time. There was no difference in motor function or any other cognitive domain. Taken together, these results suggest an effect, but an overall limited burden, of harboring a single GBA mutation in aging mutation carriers.

• Authors: Eileen E Moran, Cuiling Wang, Mindy Katz, Laurie Ozelius, Alison Schwartz, Jelena Pavlovic, Roberto A Ortega, Richard B Lipton, Molly E Zimmerman, Rachel Saunders-Pullman
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 58 Pg. 239.e1-239.e7 (10 2017) ISSN: 1558-1497 [Electronic] United States
• PMID: 28728889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Glucosylceramidase

Topics

• Aged
• Aged, 80 and over
• Cognition (physiology)
• Female
• Genetic Association Studies
• Glucosylceramidase (genetics)
• Heterozygote
• Humans
• Lewy Body Disease (genetics)
• Male
• Motor Activity (genetics, physiology)
• Mutation (genetics)
• Parkinson Disease (genetics)
• Risk Factors