Background: The impact of late-life weight changes on incident dementia is unclear. We aimed to investigate the associations of body mass index (BMI) and weight changes with dementia and to explore the role of APOE ɛ4 in these associations.

Methods: A total of 1 673 dementia-free participants aged ≥60 and older were followed for an initial 6 years to detect changes in BMI/weight and then for an additional 6 years to detect incident dementia. BMI change ([BMI_{first 6-year follow-up} - BMI_baseline]/BMI_baseline) was categorized as stable (≤5%), and moderate (5%-10%) or large (>10%) gain or loss. Weight change (weight_{first 6-year follow-up} - weight_baseline) was categorized as stable (≤2.5 kg), and moderate (2.5-7.5 kg) or large (>7.5 kg) gain or loss. Dementia was diagnosed following standard criteria. Data were analyzed using Cox regression models.

Results: Over the second 6-year follow-up period, 102 incident dementia cases were identified. Compared with stable BMI, the hazard ratios (95% CI) of dementia were 2.61 (1.09-5.54) and 2.93 (1.72-4.91) for BMI gain or loss >10%, respectively. The risk of dementia was higher among APOE ɛ4 carriers experiencing a large BMI gain (9.93 [3.49-24.6]) or loss (6.66 [2.83-14.4]) than APOE ɛ4 noncarriers with stable BMI. Similar results were observed for weight change and dementia associations.

Conclusions: BMI and weight changes showed U-shaped associations with dementia risk. Large bodyweight gain and loss alike are associated with an almost 3-fold higher risk of dementia, which may be amplified by APOE ɛ4.