{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hessl D"],"funding":["NICHD NIH HHS","NIMH NIH HHS","NINDS NIH HHS","National Institute of Child Health and Human Development"],"pagination":["519-525"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11268876"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(3)"],"pubmed_abstract":["<h4>Background</h4>Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies has made it difficult to address this hypothesis.<h4>Objective</h4>To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS.<h4>Methods</h4>This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well-matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty-four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.<h4>Results</h4>Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self-report executive function problems at baseline significantly predicted later development of FXTAS.<h4>Conclusions</h4>Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society."],"journal":["Movement disorders : official journal of the Movement Disorder Society"],"pubmed_title":["FMR1 Carriers Report Executive Function Changes Prior to Fragile X-Associated Tremor/Ataxia Syndrome: A Longitudinal Study."],"pmcid":["PMC11268876"],"funding_grant_id":["R01 HD036071","P50 HD103526","P50HD103526","R01 MH078041","HD036071","R01 NS110100"],"pubmed_authors":["Famula J","Mandujano Rojas K","Espinal G","Schneider A","Hessl D","Ferrer E","Rivera SM","Hagerman R","Tassone F"],"additional_accession":[]},"is_claimable":false,"name":"FMR1 Carriers Report Executive Function Changes Prior to Fragile X-Associated Tremor/Ataxia Syndrome: A Longitudinal Study.","description":"<h4>Background</h4>Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies has made it difficult to address this hypothesis.<h4>Objective</h4>To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS.<h4>Methods</h4>This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well-matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty-four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.<h4>Results</h4>Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self-report executive function problems at baseline significantly predicted later development of FXTAS.<h4>Conclusions</h4>Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-18T12:54:12.336Z","creation":"2025-04-04T01:12:06.902Z"},"accession":"S-EPMC11268876","cross_references":{"pubmed":["38124331"],"doi":["10.1002/mds.29695"]}}