Physical Activity and AD-Related Pathology—Reply

In reply

We agree that sample limitations such as selection bias or power may explain why we did not find an association between physical exercise and beta-amyloid (Aβ) deposition. However, there are a number of other factors that may account for inconsistencies in reported associations with lifestyle factors. As Wang et al¹ pointed out in their recent meta-analysis, lifestyle factors such as cognitive, physical, and social activity levels are challenging to quantify. The study populations being tested (normal older individuals vs patients with AD), the time course of measurements (lifetime history vs current activity levels), and differing measurement scales all likely contribute to variability between study findings. We would also like to note that the studies cited by Dr Wang link lifestyle factors with severity of dementia, while our study links activity level with Aβ deposition in a cognitively normal population. This is important because studies that include patients with dementia make it possible to test the cognitive reserve hypothesis, which predicts that engagement in stimulating activities prolongs normal cognitive functioning despite the presence of pathology. Our study addresses a different issue, which is the development of the AD pathology itself.