On 2014 Aug 01, Mark Yarchoan commented:

Overall, this study raises interest in a link between metabolic derangements and Alzheimer’s disease (AD). However, one concern I have is that in evaluating a possible association between low circulating leptin and incident dementia, the authors adjusted for current BMI, but not amount or direction of recent weight change. It is well known (and reiterated in this article) that, “Although midlife obesity is associated with an increased risk of AD, late-life weight loss is known to precede the onset of clinical AD.” Therefore, it is to be expected that the AD and normal groups might have similar overall weight and BMI, but a different direction and rate of BMI change (AD group rapidly losing weight, normal aging group keeping or gaining weight). Leptin levels are correlated with current body fat mass, but appear to be even more significantly affected by direction of weight change. For example, 14% intentional weight loss in human subjects results in a 64.5% reduction in leptin levels (Sumithran et al. NEJM 2014/ PMID: 22029981). Therefore, I am concerned that the observed differences in leptin levels in this study may simply be a consequence of the significant and early weight loss seen in AD.

On 2014 Aug 01, Mark Yarchoan commented:

Overall, this study raises interest in a link between metabolic derangements and Alzheimer’s disease (AD). However, one concern I have is that in evaluating a possible association between low circulating leptin and incident dementia, the authors adjusted for current BMI, but not amount or direction of recent weight change. It is well known (and reiterated in this article) that, “Although midlife obesity is associated with an increased risk of AD, late-life weight loss is known to precede the onset of clinical AD.” Therefore, it is to be expected that the AD and normal groups might have similar overall weight and BMI, but a different direction and rate of BMI change (AD group rapidly losing weight, normal aging group keeping or gaining weight). Leptin levels are correlated with current body fat mass, but appear to be even more significantly affected by direction of weight change. For example, 14% intentional weight loss in human subjects results in a 64.5% reduction in leptin levels (Sumithran et al. NEJM 2014/ PMID: 22029981). Therefore, I am concerned that the observed differences in leptin levels in this study may simply be a consequence of the significant and early weight loss seen in AD.