title: Age and CGG-repeat length are associated with neuromotor impairments in at-risk females with the FMR1 premutation.
abstract: Recent studies report a higher risk of dementia and motor symptoms in females with the fragile X mental retardation 1 premutation (PM-carriers) than has hitherto been appreciated. Here, we use dual-task gait paradigms to identify potential markers of cognitive and motor decline in female PM-carriers. Spatiotemporal gait characteristics and variability of gait were assessed during single- and dual-task conditions in 28 female PM-carriers (mean age 41.32 ± 8.03 years) and 31 female controls with normal fragile X mental retardation 1 alleles (mean age 41.61 ± 8.30 years). Despite comparable gait characteristics at baseline, gait performance was significantly poorer for PM-carriers when performing concurrent working memory tasks (counting backwards by 3's or 7's) when compared with controls. Correlational analyses showed that low working memory capacity was significantly associated with dual-task interference for the gait domains of pace (speed, step length) and variability (step time, swing time) in PM-carriers. Multiple regression analyses further showed that the interaction between age and CGG repeat length was strongly predictive of gait variability during dual-task performance. These findings indicate for the first time that vulnerability in specific domains of gait control may act as sensitive surrogate markers of future decline in female PM-carriers.
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Claudine M
authors.initials: CM
authors.lastname: Kraan
authors.affiliation: Olga Tennison Research Centre, School of Psychological Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Hocking
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Metcalfe
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia; Victorian Clinical Genetics Services, Parkville, Victoria, Australia.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Archibald
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
authors.affiliation: Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia; Centre for Health Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Trollor
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Bradshaw
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Centre for Developmental Disability Health Victoria, Monash University, Clayton, Victoria, Australia; Fragile X Alliance Inc (Clinic and Resource Centre), North Caufield, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: kim.cornish@monash.edu.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cornish
mesh_terms: D000328:Adult; D000375:Aging; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005684:Gait; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008570:Memory, Short-Term; D008875:Middle Aged; D009154:Mutation; D011596:Psychomotor Disorders / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D011597:Psychomotor Performance; D012044:Regression Analysis; D012306:Risk; D018911:Trinucleotide Repeats
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Alzheimer's disease; Cerebellar motor networks; Cognitive-motor interference; Dual-task paradigm; Fragile X mental retardation gene 1 (FMR1); Fragile X mental retardation protein (FMRP); Fragile X syndrome; Fragile X tremor ataxia syndrome (FXTAS); Gait variability; Working memory