Background: Obesity has been consistently associated with dementia. The role of certain risk factors of dementia may change during life, and the importance of having a life-course perspective has been acknowledged. Objective: The aim of this study was to investigate the association of midlife and late-life body mass index (BMI) with late-life dementia/Alzheimer's disease (AD) and whether the association was independent of other obesity-related co-morbidities. Methods: The association between midlife BMI (mean age 50.2, SD 6.0) and late-life BMI (mean age 71.2, SD 4.0) and incident dementia later in life (mean age 75.7, SD 5.0) were investigated among 1,304 participants of the longitudinal population-based Cardiovascular risk factors, Aging and Dementia (CAIDE) study, conducted in Eastern Finland. The duration of follow-up was 26 years. The diagnosis of dementia was based on DSM-IV criteria and the probable and possible AD on the NINCDS-ADRDA criteria. Results: Higher midlife BMI was associated with higher risk of incident dementia (adjusted HR, 95% CI 1.07, 1.00–1.14). However, decrease in BMI from midlife to late-life was associated with higher risk of dementia (1.14, 1.03–1.25 for one-unit decrease) and AD (1.20, 1.09–1.33). High late-life BMI was associated with lower risk of AD (0.89, 0.81–0.98) but the association with dementia was less evident (0.94, 0.86–1.03). Conclusion: Higher midlife BMI is related to higher risk of dementia and AD, independently of obesity-related risk factors and co-morbidities. Steeper decrease of BMI and low late-life BMI are associated with higher risk of dementia and AD. These findings highlight the importance of life-course perspective when assessing the association between BMI and cognition.