Relationships between motor scores and cognitive functioning in FMR1 female premutation X carriers indicate early involvement of cerebello-cerebral pathways View Full Text


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Article Info

DATE

2021-06-11

AUTHORS

Elsdon Storey, Minh Q. Bui, Paige Stimpson, Flora Tassone, Anna Atkinson, Danuta Z. Loesch

ABSTRACT

BackgroundSmaller expansions of CGG trinucleotide repeats in the FMR1 X-linked gene termed ‘premutation’ lead to a neurodegenerative disorder: Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) in nearly half of aged carrier males, and 8–16% females. Core features include intention tremor, ataxia, and cognitive decline, and white matter lesions especially in cerebellar and periventricular locations. A ‘toxic’ role of elevated and expanded FMR1 mRNA has been linked to the pathogenesis of this disorder. The emerging issue concerns the trajectory of the neurodegenerative changes: is the pathogenetic effect confined to overt clinical manifestations? Here we explore the relationships between motor and cognitive scale scores in a sample of 57 asymptomatic adult female premutation carriers of broad age range.MethodsThree motor scale scores (ICARS-for tremor/ataxia, UPDRS-for parkinsonism, and Clinical Tremor) were related to 11 cognitive tests using Spearman’s rank correlations. Robust regression, applied in relationships between all phenotypic measures, and genetic molecular and demographic data, identified age and educational levels as common correlates of these measures, which were then incorporated as confounders in correlation analysis.ResultsCognitive tests demonstrating significant correlations with motor scores were those assessing non-verbal reasoning on Matrix Reasoning (p-values from 0.006 to 0.011), and sequencing and alteration on Trails-B (p-values from 0.008 to 0.001). Those showing significant correlations with two motor scores-ICARS and Clinical Tremor- were psychomotor speed on Symbol Digit Modalities (p-values from 0.014 to 0.02) and working memory on Digit Span Backwards (p-values from 0.024 to 0.011).ConclusionsSubtle motor impairments correlating with cognitive, particularly executive, deficits may occur in female premutation carriers not meeting diagnostic criteria for FXTAS. This pattern of cognitive deficits is consistent with those seen in other cerebellar disorders. Our results provide evidence that more than one category of clinical manifestation reflecting cerebellar changes – motor and cognitive - may be simultaneously affected by premutation carriage across a broad age range in asymptomatic carriers. More... »

PAGES

15

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40673-021-00138-0

DOI

http://dx.doi.org/10.1186/s40673-021-00138-0

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https://app.dimensions.ai/details/publication/pub.1138788187

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34116720


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