Reduced Sensorimotor, Working Memory, and Episodic Memory Abilities in Aging Female FMR1 Premutation Carriers with and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).

BACKGROUND/

OBJECTIVES

Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor, gait ataxia, and cerebellar white matter degeneration, along with possible cognitive and cerebral changes. Although diagnostic criteria were originally developed in males, emerging evidence suggests that FXTAS may present differently in females. The present study examined sensorimotor and memory features of aging in female premutation carriers with (FXTAS+) and without FXTAS (FXTAS-).

METHODS

We studied 51 female premutation carriers (FXTAS+ = 16, FXTAS- = 35) and 24 age-matched female controls. Participants ranged in age from 47-80 years. All participants completed genetic testing, clinical evaluations, T2-weighted MRIs, and quantitative assessments of sensorimotor (precision grip force task) and memory (reading span; visual paired associates task) functions.

RESULTS

During precision grip testing, FXTAS+ carriers showed higher sustained force regularity than FXTAS- carriers (p = 0.03, d = 1.0) and controls (p = 0.004, d = 1.1) at low gain levels only. FXTAS+ participants were slower than controls on motor reaction time (p = 0.009, d = 0.82). Initial force output was higher in FXTAS+ than FXTAS- carriers (p = 0.03, d = 1.0) and controls (p = 0.03, d = 1.0) but at low gain only. FXTAS+ carriers exhibited poorer working memory than FXTAS- carriers (p = 0.03, d = 0.91) and controls (p = 0.02, d = 1.0). During a long-term memory task, FXTAS+ participants were less accurate than FXTAS- carriers (p = 0.04, d = 0.86) and controls (p = 0.004, d = 1.1) and showed increased reaction times relative to FXTAS- carriers (p = 0.03, d = -0.82) and controls (p = 0.01, d = -1.2).

CONCLUSIONS

Together, these findings indicate that FXTAS+ females exhibit distinct motor and cognitive impairments, underscoring the value of quantitative behavioral measures for detecting and tracking neurodegenerative progression in female premutation carriers.