. Effect of intellectual enrichment on AD biomarker trajectories: Longitudinal imaging study. Neurology. 2016 Mar 22;86(12):1128-35. Epub 2016 Feb 24 PubMed.


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  1. I think the authors did a very good job highlighting why we should be cautious in the interpretation of these results. First, in regard to assessing physical activity, this was done by self-report, and, if I understood this correctly, the participants were asked to recall their level of physical activity in midlife. Since these participants were aged 70-89 years at the time of the questionnaire, we need to consider the accuracy of this information. The same concern is applicable to the midlife cognitive activity.

    Thus, the finding of minimal effects of lifestyle enrichment on AD biomarker trajectories for the overall cohort needs to be thoughtfully considered. The lack of any great effect may be due to how the enrichment components were measured (i.e., rough/recall estimates versus more accurate measure).

    They did find that education was neuroprotective, as has been consistently reported. Notably, since it’s a matter of record, it is much easier for a person to accurately report his or her level of education than his or her midlife physical/cognitive activity.

    It is clear from this and other studies that PET imaging certainly offers us the opportunity to quantify AD-related biomarkers in vivo and investigate factors that might mitigate them. 

    View all comments by Teresa Liu-Ambrose
  2. I absolutely agree with the comments about self-report questionnaires. However, to understand the true causal effect of midlife cognitive and physical activities, we will need controlled intervention trials run over sufficiently long periods of time. Our study results suggesting a differential effect of education level on pathology trajectories will be important to consider when designing these future trials.

    View all comments by Prashanthi Vemuri
  3. I have been hearing about the need for longitudinal studies for decades. The problem is that by the time these studies are completed, many of the people who would have benefited from the data will already be hospitalized with AD. The results from animal models and findings from retrospective human studies and even case reports provide sufficient clues to lifestyle and environmental factors that may modify the progression of neurodegenerative disease. If these changes in lifestyle etc. have no negative consequences—and possible additional benefits such as an overall improvement in general well-being—then recommending that patients adopt these behaviors sooner rather than later is always the prudent thing to do.

    View all comments by Marcia Ratner

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