Women with a premutation allele of the FMR1 gene are more susceptible to various age-related symptoms and diseases, including a decrease in some cognitive functions. However, the risk factors for age-related deterioration, including the potential influence of family history and genetic variables, are unknown. Syntactic complexity declines early in various forms of pathological aging, which predicts the advent of neurodegenerative illness later. For a study, the researchers characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, as well as associations with a family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length, to shed light on the earliest signs of degeneration. 55 women with the FMR1 premutation who were 35–64 years old at the start of the practice took part in 1–5 longitudinal examinations spaced about a year apart (130 observations total). All of the women in the practice were moms of children who had been diagnosed with fragile X syndrome. Participants supplied information on their family history of FXTAS, and language samples were examined for syntactic complexity. Molecular genetic testing was used to establish the length of the CGG repeats. Women with a family history of FXTAS had a faster age-related drop in syntactic complexity than women without a family history, according to hierarchical linear models, with the difference becoming apparent in their mid-50s. The length of CGG repeats was not a significant predictor of age-related change. The findings show that women with the FMR1 premutation who have a family history of FXTAS are more likely to develop neurodegenerative illness, as determined by age-related syntactic complexity loss. As a result, a family history of FXTAS could be a unique risk factor for age-related disease. A follow-up investigation is needed to see if the syntactic decline is a specific early sign of FXTAS rather than a more general age-related cognitive decline linked to the FMR1 premutation.
Link:link.springer.com/article/10.1186/s11689-022-09415-3
