Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation
Abstract 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-022-09415-3 |
| _version_ | 1818753241610977280 |
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| author | Jessica Klusek Amanda Fairchild Carly Moser Marsha R. Mailick Angela John Thurman Leonard Abbeduto |
| author_facet | Jessica Klusek Amanda Fairchild Carly Moser Marsha R. Mailick Angela John Thurman Leonard Abbeduto |
| author_sort | Jessica Klusek |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-18T05:04:14Z |
| format | Article |
| id | doaj.art-2e3dde62e87046c0a7b9bd622a2c3314 |
| institution | Directory Open Access Journal |
| issn | 1866-1947 1866-1955 |
| language | English |
| last_indexed | 2024-12-18T05:04:14Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-2e3dde62e87046c0a7b9bd622a2c33142022-12-21T21:20:03ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552022-01-0114111310.1186/s11689-022-09415-3Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutationJessica Klusek0Amanda Fairchild1Carly Moser2Marsha R. Mailick3Angela John Thurman4Leonard Abbeduto5Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South CarolinaDepartment of Psychology, University of South CarolinaDepartment of Communication Sciences and Disorders, Arnold School of Public Health, University of South CarolinaWaisman Center, University of Wisconsin-MadisonDepartment of Psychiatry and Behavioral Sciences and MIND Institute, University of California Davis HealthDepartment of Psychiatry and Behavioral Sciences and MIND Institute, University of California Davis HealthAbstract 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.https://doi.org/10.1186/s11689-022-09415-3Grammatical complexityLanguage productionAgingFragile X premutation |
| spellingShingle | Jessica Klusek Amanda Fairchild Carly Moser Marsha R. Mailick Angela John Thurman Leonard Abbeduto Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation Journal of Neurodevelopmental Disorders Grammatical complexity Language production Aging Fragile X premutation |
| title | Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation |
| title_full | Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation |
| title_fullStr | Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation |
| title_full_unstemmed | Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation |
| title_short | Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation |
| title_sort | family history of fxtas is associated with age related cognitive linguistic decline among mothers with the fmr1 premutation |
| topic | Grammatical complexity Language production Aging Fragile X premutation |
| url | https://doi.org/10.1186/s11689-022-09415-3 |
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