Five-Year Change in Body Mass Index Predicts Conversion to Mild Cognitive Impairment or Dementia Only in APOE ε4 Allele Carriers

Background: Body mass index (BMI) has been identified as an important modifiable lifestyle risk factor for dementia, but less is known about how BMI might interact with Apolipoprotein E epsilon 4 (APOE epsilon 4) carrier status to predict conversion to mild cognitive impairment (MCI) and dementia. Objective: The aim of this study was to investigate the interaction between APOE epsilon 4 status and baseline (bBMI) and five-year BMI change (bBMI) on conversion to MCI or dementia in initially cognitively healthy older adults. Methods: The associations between bBMI, Delta BMI, APOE epsilon 4 status, and conversion to MCI or dementia were investigated among 1,289 cognitively healthy elders from the National Alzheimer's Coordinating Center (NACC) database. Results: After five years, significantly more carriers (30.6%) converted to MCI or dementia than noncarriers (17.6%), p < 0.001, OR = 2.06. Neither bBMI (OR = 0.99, 95% CI = 0.96-1.02) nor the bBMI by APOE interaction (OR = 1.02, 95% CI = 0.96-1.08) predicted conversion. Although Delta BMI also did not significantly predict conversion (OR = 0.90, 95% CI = 0.78-1.04), the interaction between Delta BMI and carrier status was significant (OR = 0.72, 95% CI = 0.53-0.98). For carriers only, each one-unit decline in BMI over five years was associated with a 27% increase in the odds of conversion (OR = 0.73, 95% CI = 0.57-0.94). Conclusion: A decline in BMI over five years, but not bBMI, was strongly associated with conversion to MCI or dementia only for APOE epsilon 4 carriers. Interventions and behaviors aimed at maintaining body mass may be important for long term cognitive health in older adults at genetic risk for AD.