The cognitive profile of hereditary spastic paraplegia: a systematic review of the literature

Background: Hereditary Spastic Paraplegia (HSP) is a heterogeneous group of genetic diseases characterized by involvement of the corticospinal bundle. In addition to motor manifestations, the phenotypic spectrum of HSP can also include cognitive disorders. Our aim was to examine the cognitive profile of patients with HSP and investigate potential subtype-phenotype associations on the basis of a systematic review of the literature. Methods: Following PRISMA criteria, Pubmed, Cochrane Libraries, APA PsycInfo, Scopus, and Web of Science were searched for studies performing a comprehensive neuropsychological assessment in patients with pure or complex HSP and different Spastic Paraplegia Genes (SPG). Results: A total of 343 articles were selected, among which 38 met the eligibility criteria for inclusion. The occurrence and the degree of cognitive impairment varied significantly, depending on the specific clinical and genetic HSP subtype. Global cognitive functioning was more severely compromised in complex forms of HSP (such as SPG11), whereas pure forms (such as SPG4) may show more subtle cognitive impairment. Overall, executive functions appeared to be the most affected cognitive domain in both conditions. Discussion: Given the high prevalence of cognitive impairment in HSP patients, it is desirable to incorporate a standardized neuropsychological assessment into routine clinical practice. Therefore, we propose a potential neuropsychological assessment protocol to address the cognitive deficits most frequently observed in this clinical population and provide a framework for future research.