TY - JOUR
T1 - Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers
AU - Hippolyte, Loyse
AU - Battistella, Giovanni
AU - Perrin, Aline G.
AU - Fornari, Eleonora
AU - Cornish, Kim M.
AU - Beckmann, Jacques S.
AU - Niederhauser, Julien
AU - Vingerhoets, François J.G.
AU - Draganski, Bogdan
AU - Maeder, Philippe
AU - Jacquemont, Sébastien
N1 - Funding Information:
The authors are indebted to all the families and individuals who participated in this study. Special thanks to the UK Fragile X Society and the Association Nationale du Syndrome de l'X Fragile, le Goéland for their precious collaboration. The authors acknowledge Nathalie Isidor, Gaetan Lesca, and Francesca Forzano for their contribution in the recruitment of the participants. The study was supported by the Swiss National Fund 320030_122674 , the Synapsis Foundation, Switzerland as well as the “Centre d'Imagerie BioMédicale” (CIBM) which is a research initiative of the following partners: University of Lausanne, Swiss Federal Institute of Technology Lausanne, University of Geneva, Centre Hospitalier Universitaire Vaudois, Hôpitaux Universitaires de Genève, and the Leenaards and the Jeantet Foundations. S.J. was supported by a grant from the Faculté de Biologie et de Médecine, Relève Académique. B.D. was supported by the Swiss National Science Foundation (NCCR Synapsy , project grant Nr 320030_135679 and SPUM 33CM30_140332/1), Foundation Parkinson Switzerland, Foundation Synapsis, Novartis Foundation for medical–biological research and Deutsche Forschungsgemeinschaft (Kfo 247).
PY - 2014/8
Y1 - 2014/8
N2 - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.
AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.
KW - Asymptomatic male carriers of FMR1 premutation
KW - Diffusion tensor imaging
KW - Dorsolateral prefrontal cortex
KW - Executive functions
KW - Hippocampal white matter alterations
KW - Verbal memory
UR - https://www.scopus.com/pages/publications/84899903431
U2 - 10.1016/j.neurobiolaging.2014.01.150
DO - 10.1016/j.neurobiolaging.2014.01.150
M3 - Article
C2 - 24612675
AN - SCOPUS:84899903431
SN - 0197-4580
VL - 35
SP - 1939
EP - 1946
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 8
ER -