Exploring the Incidence of Cognitive Dysfunction and Sleep Disorders in Charcot-Marie-Tooth

Abstract Background: Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous peripheral neuropathy traditionally considered to spare the central nervous system (CNS). However, recent reports suggest possible CNS involvement, including cognitive impairment and sleep disturbances. The true prevalence of these manifestations remains unclear due to limited large-scale data. Methods: We conducted a retrospective cohort study using data from 141 healthcare organizations within the Global Collaborative Network. Patients aged ≤50 years with a diagnosis of hereditary motor and sensory neuropathy (ICD-10: G60.0) were included. Exclusion criteria comprised conditions that independently contribute to cognitive or sleep disorders. Diagnoses of cognitive impairment and sleep disorders were identified using standardized ICD-10 codes. Results: Among 11,795 patients, 466 (3.95%) were diagnosed with cognitive impairment and 791 (6.71%) with sleep disorders. Cognitive impairment was more common in females (4.34%) than males (3.56%), with peak incidence in the 25–29 age group (6.2%). Sleep disorders also showed higher prevalence in females (7.51%) versus males (5.91%), peaking similarly in the 25–29 age group (11.9%). Striking racial disparities were noted: Native Hawaiian/Pacific Islander and American Indian/Alaska Native patients had the highest prevalence of both conditions (41.7% and 25.6%, respectively). These patterns suggest underrecognized CNS involvement in CMT across diverse subgroups. Conclusion: Cognitive dysfunction and sleep disorders occur at clinically significant rates in patients with CMT, particularly among younger adults and racially minoritized populations. These findings highlight the need for expanded clinical screening and further mechanistic studies to understand CNS involvement in CMT.