APOE ε4 Allele is Associated with Cognitive Impairment in Chinese Sporadic ALS: A Retrospective Cohort Study.

Objective: To evaluate the effects of apolipoprotein E (APOE) genotype and serum APOE levels on cognitive and motor phenotypes in Chinese patients with sporadic amyotrophic lateral sclerosis (ALS). Methods: APOE genotypes were determined in 289 patients with sporadic ALS, and serum APOE levels were measured in a subset of 222 patients. Cognitive function was assessed using the Edinburgh Cognitive and Behavioural ALS Screen. We examined the association of APOE genotype and serum levels with age at onset, site of onset, disease progression rate (DPR), time to generalization of symptoms (TTG), and cognitive performance. Results: No significant differences were observed in sex, age at onset, site of onset, DPR, or TTG among patients with different APOE genotypes. Similarly, serum APOE levels did not correlate with these clinical variables. However, the APOE-ε4 allele was associated with lower ALS-specific cognitive scores, particularly in the domain of verbal fluency. Conclusion: Our study provides preliminary evidence linking the APOE-ε4 allele to cognitive impairment, particularly in language fluency, among Chinese patients with ALS. These findings support the hypothesis that APOE genotype contributes to ALS etiology and suggest its role in shaping distinct cognitive phenotypes in the disease.