Cognitive impairment in hereditary spastic paraparesis: An overlooked aspect of a motor disorder

Introduction: Hereditary spastic paraparesis (HSP) are a group of disabling neurological disorders classically defined by progressive spasticity and weakness at lower limbs. Non-motor symptoms may be part of the clinical phenotype. Our aim was to evaluate cognitive abilities, especially executive functions and verbal memory, in different forms of HSP. Material and methods: This study included 40 patients and 25 matched healthy controls (HC). Among the patients, 18 had SPG4, 6 SPG7, 2 SPG5, 3 SPG11, 3 SPG10, 3 SPG28, and one each had SPG3A, SPG9, SPG15, SPG17 and SPG21. Disease severity was assessed using the Spastic Paraplegia Rating Scale (SPRS). To evaluate cognitive domains, a defined neuropsychological battery was used. Statistical methods included Shapiro–Wilk testing to determine distribution, followed by t-tests, Mann–Whitney U, ANOVA, or Kruskal–Wallis tests as appropriate, with false discovery rate (FDR) correction. Effect sizes were calculated using Cohen’s d, rank-biserial correlation (rb) or η2. Pearson’s (r) or Spearman’s rank correlation coefficient (ρ) were used to explore associations. Results: No significant differences emerged in age or education. While MMSE scores were slightly lower in patients, major impairments were found in executive function, attention, and memory (all p < 0.001, FDR-corrected). Cognitive deficits were independent of mood, fatigue, and pain. Patients with complicated HSP (cHSP) showed greater impairment than those with pure HSP (pHSP). SPG4 patients exhibited specific deficits despite preserved global cognition. Conclusion: Cognitive impairment is a relevant but underrecognized feature in HSP. Comprehensive neuropsychological testing is critical, as global screening may miss relevant deficits.