Twelve-year nationwide cohort study identifying risk factors for conversion from mild cognitive impairment to Alzheimer’s disease

Mild cognitive impairment (MCI) is a pre-dementia phase preceding dementia of the Alzheimer's type (DAT). Despite numerous studies exploring the risk factors for the conversion from MCI to DAT, the results have been heterogeneous. This study aimed to investigate the incidence of the conversion from MCI to DAT and the risk factors contributing to DAT conversion in Korean patients with MCI. A 12-year nationwide retrospective study was conducted. We enrolled patients with MCI aged ≥ 40 years between 2009 and 2015 and followed them up until 2020. The incidence of DAT conversion based on age at MCI diagnosis and its risk factors were analyzed using Cox proportional hazards regression. The conversion rate of DAT in patients with MCI increased during the age range of 70 to 90 years, and approached a plateau near the age of 100 years. Being underweight (hazard ratio [HR] 1.279, 95% confidence interval [CI] 1.223-1.338) was associated with a higher risk of DAT conversion. Cardiometabolic diseases (diabetes, HR 1.373, 95% CI 1.342-1.406; coronary heart disease, HR 1.047, 95% CI 1.015-1.079; and hemorrhagic stroke, HR 1.342, 95% CI 1.296-1.390;) increased the risk of DAT conversion, whereas hypertension, ischemic stroke, and dyslipidemia did not. Depression (HR 1.736, 95% CI 1.700-1.773) and physical inactivity (HR 1.193, 95% CI 1.161-1.227) were related to the increased risk. Mild (HR 0.860, 95% CI 0.830-0.891) to moderate (HR 0.880, 95% CI 0.837-0.926) alcohol consumption, high income (HR 0.947, 95% CI 0.925-0.970), and urban residence (HR 0.889, 95% CI 0.872-0.907) were associated with the decreased risk of DAT conversion. Multiple modifiable risk factors were closely associated with an increased risk of DAT conversion. Our results may help in designing preventive strategies to mitigate the risk of DAT conversion in patients with MCI.