Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation.
Aging
Fragile X premutation
Grammatical complexity
Language production
Journal
Journal of neurodevelopmental disorders
ISSN: 1866-1955
Titre abrégé: J Neurodev Disord
Pays: England
ID NLM: 101483832
Informations de publication
Date de publication:
14 01 2022
14 01 2022
Historique:
received:
30
04
2021
accepted:
02
01
2022
entrez:
14
1
2022
pubmed:
15
1
2022
medline:
22
3
2022
Statut:
epublish
Résumé
Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation.
Sections du résumé
BACKGROUND
Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length.
METHODS
Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing.
RESULTS
Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change.
CONCLUSIONS
Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation.
Identifiants
pubmed: 35026985
doi: 10.1186/s11689-022-09415-3
pii: 10.1186/s11689-022-09415-3
pmc: PMC8903682
doi:
Substances chimiques
FMR1 protein, human
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7Subventions
Organisme : NIH HHS
ID : R21DC017804
Pays : United States
Organisme : NIH HHS
ID : R03HD098291
Pays : United States
Organisme : NIH HHS
ID : F32DC013934
Pays : United States
Organisme : NICHD NIH HHS
ID : R03 HD098291
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD024356
Pays : United States
Organisme : NIH HHS
ID : P50HD103526
Pays : United States
Organisme : NIDCD NIH HHS
ID : R21 DC017804
Pays : United States
Organisme : NIDCD NIH HHS
ID : F32 DC013934
Pays : United States
Organisme : NIH HHS
ID : R01HD024356
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Psychol Aging. 2001 Dec;16(4):600-14
pubmed: 11766915
Neuropsychologia. 2008 Jan 15;46(1):12-21
pubmed: 17897685
Am J Med Genet B Neuropsychiatr Genet. 2012 Jul;159B(5):589-97
pubmed: 22619118
Hum Reprod. 2007 Aug;22(8):2142-52
pubmed: 17588953
J Mol Diagn. 2010 Sep;12(5):589-600
pubmed: 20616364
Neurosci Biobehav Rev. 2009 Sep;33(8):1168-77
pubmed: 19747595
J Clin Exp Neuropsychol. 2008 Jul;30(5):501-56
pubmed: 18569251
Brain Cogn. 2020 Mar;139:105511
pubmed: 31887710
J Clin Endocrinol Metab. 2012 Sep;97(9):E1686-94
pubmed: 22730514
BMC Med. 2019 Feb 27;17(1):47
pubmed: 30808345
Front Aging Neurosci. 2018 Jan 09;9:437
pubmed: 29375365
Am J Med Genet B Neuropsychiatr Genet. 2013 Jul;162B(5):466-73
pubmed: 23740716
Brain. 2010 Aug;133(Pt 8):2210-6
pubmed: 20826429
Psychoneuroendocrinology. 2010 May;35(4):516-24
pubmed: 19811879
Psychol Aging. 2001 Jun;16(2):227-39
pubmed: 11405311
Am J Med Genet A. 2008 Mar 15;146A(6):720-9
pubmed: 18266246
Free Radic Biol Med. 2021 Mar;165:100-110
pubmed: 33497798
Mov Disord. 2000 May;15(3):516-23
pubmed: 10830418
Genet Med. 2020 Apr;22(4):758-766
pubmed: 31896764
Am J Med Genet A. 2012 Oct;158A(10):2473-81
pubmed: 22903889
Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):130-9
pubmed: 18553360
Front Cell Neurosci. 2015 Feb 27;9:58
pubmed: 25774124
PLoS One. 2015 Apr 09;10(4):e0119424
pubmed: 25856161
Biol Psychiatry. 2016 May 15;79(10):850-857
pubmed: 26300270
Front Hum Neurosci. 2011 Jul 14;5:63
pubmed: 21808616
Int J Neurosci. 1996 Oct;87(1-2):71-8
pubmed: 8913820
Clin Neuropsychol. 2018 Aug - Oct;32(7):1337-1352
pubmed: 28972453
Brain. 2008 Jan;131(Pt 1):8-38
pubmed: 17947337
Behav Res Methods Instrum Comput. 2004 May;36(2):193-202
pubmed: 15354684
Clin Linguist Phon. 2014 Mar;28(3):195-207
pubmed: 24093162
Front Genet. 2018 Aug 24;9:344
pubmed: 30197656
Eur J Hum Genet. 2009 Oct;17(10):1359-62
pubmed: 19367323
Nat Rev Neurol. 2016 Jul;12(7):403-12
pubmed: 27340021
Brain Cogn. 2021 Mar;148:105675
pubmed: 33387817
Genet Med. 2018 Dec;20(12):1627-1634
pubmed: 29595813
Am J Hum Genet. 2012 Apr 6;90(4):579-90
pubmed: 22482801
Psychiatry Res. 1986 Mar;17(3):203-12
pubmed: 3704028
BMC Med Genet. 2014 Oct 28;15:119
pubmed: 25348928
JAMA. 1996 Feb 21;275(7):528-32
pubmed: 8606473
Am J Med Genet B Neuropsychiatr Genet. 2013 Dec;162B(8):872-8
pubmed: 24003006
J Autism Dev Disord. 2019 Jan;49(1):197-208
pubmed: 30097759
Int J Behav Dev. 2012 Jan;36(1):53-61
pubmed: 22798702
J Speech Lang Hear Res. 2019 Mar 25;62(3):706-722
pubmed: 30950734
JAMA. 2004 Jan 28;291(4):460-9
pubmed: 14747503
Genet Med. 2001 May-Jun;3(3):200-5
pubmed: 11388762
J Autism Dev Disord. 2019 Mar;49(3):960-977
pubmed: 30382442
Am J Med Genet A. 2008 Apr 15;146A(8):1009-16
pubmed: 18348275
Mov Disord. 2019 Jun;34(6):801-811
pubmed: 31091353
Genet Med. 2013 Aug;15(8):639-42
pubmed: 23492875
Brain Lang. 1989 Nov;37(4):628-42
pubmed: 2479447
Exp Gerontol. 2009 Jan-Feb;44(1-2):46-50
pubmed: 18620039
J Int Neuropsychol Soc. 2020 Feb;26(2):226-240
pubmed: 31727185
Maturitas. 2006 Mar 20;53(4):447-53
pubmed: 16198073
J Gerontol B Psychol Sci Soc Sci. 2003 Sep;58(5):P260-8
pubmed: 14507932
Lancet. 2017 Dec 16;390(10113):2673-2734
pubmed: 28735855
Sci Rep. 2017 Jun 1;7(1):2674
pubmed: 28572606
J Autism Dev Disord. 2012 Sep;42(9):1836-46
pubmed: 22167342
J Neurodev Disord. 2017 Aug 24;9(1):31
pubmed: 28835209
Psychol Aging. 2001 Jun;16(2):312-22
pubmed: 11405318
Neurobiol Aging. 2005 Mar;26(3):341-7
pubmed: 15639312
J Cult Divers. 2009 Fall;16(3):127-35
pubmed: 19824292
Cerebellum. 2016 Oct;15(5):565-9
pubmed: 27126308
Sci Adv. 2019 Aug 21;5(8):eaaw7195
pubmed: 31457090
Curr Alzheimer Res. 2013 Jul;10(6):642-53
pubmed: 23627757
Semin Reprod Med. 2011 Jul;29(4):299-307
pubmed: 21969264
Neurosci Biobehav Rev. 2008 Aug;32(6):1103-20
pubmed: 18436304
Front Genet. 2015 Jun 03;6:192
pubmed: 26089834
Rheumatology (Oxford). 2011 Dec;50(12):2233-6
pubmed: 21926154
Mov Disord. 2018 Apr;33(4):628-636
pubmed: 29389022
Behav Res Methods. 2011 Mar;43(1):136-44
pubmed: 21287110
Biometrics. 1997 Sep;53(3):983-97
pubmed: 9333350
Brain Cogn. 2011 Apr;75(3):255-60
pubmed: 21295394
Brain Cogn. 2013 Jun;82(1):84-9
pubmed: 23523717
Clin Genet. 2010 Jul;78(1):38-46
pubmed: 20497189
Am J Med Genet B Neuropsychiatr Genet. 2014 Dec;165B(8):705-11
pubmed: 25346430
Neurosci Biobehav Rev. 2013 Mar;37(3):522-47
pubmed: 23352653
Front Psychiatry. 2019 May 07;10:199
pubmed: 31133885
J Clin Exp Neuropsychol. 2018 Nov;40(9):917-939
pubmed: 29669461
Am J Med Genet B Neuropsychiatr Genet. 2012 Sep;159B(6):660-8
pubmed: 22693142
Dev Med Child Neurol. 2019 Feb;61(2):121-127
pubmed: 30084485