Current evidence shows that apolipoprotein E (APOE), apolipoprotein CI (APOC1) and low density lipoprotein receptor-related protein (LRP) variations are related to late-onset Alzheimer’s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer’s disease patients. We performed a 30-month longitudi-nal cohort study to investigate the relationship between Alzheimer’s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer’s disease were recruit-ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa-tients’ cognitive function. After a 30-month follow-up period, we found a signiifcant reduction in Mini-Mental State Examination total score, a higher proportion of patients fuliflling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOEε4 carriers compared with non-carriers. In addition, the APOEε4 allele frequency was signiifcantly higher in the cognitive impairment progression group compared with the non-cognitive im-pairment progression group. In conclusion, APOEε4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOEε4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer’s disease.