The effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.