Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

In this large randomized clinical trial of weight loss in obesity and type 2 diabetes, we found that the effect of weight loss on the brain in women with obesity and type 2 diabetes differed by menopausal status and APOE status. Women with obesity and cardiovascular risk factors who lost around 10% of their weight 10 years after menopause had worse cognitive performance compared to matched controls. In contrast, when women lost weight before or early after menopause, their cognitive functions were better than their matched controls. These benefits were only seen in APOE4 non-carriers. Our study underscores the importance of timing and APOE genotype. As our blood vessels and brain cells age, losing weight may deprive our body of essential nutrients. Weight loss in older APOE4 carriers may not be a good idea. 

In the above figure, the composite cognitive score differed based on when women lost weight. Women who lost weight before or within 5 years of menopause had better scores when they lost weight (ILI or intensive lifestyle arm) compared to the those in the control group (DSE or Diabetes Support and Education). The opposite effect was seen in women who lost weight 10 years after menopause.