Müller S, Preische O, Sohrabi HR, Gräber S, Jucker M, Ringman JM, Martins RN, McDade E, Schofield PR, Ghetti B, Rossor M, Fox NN, Graff-Radford NR, Levin J, Danek A, Vöglein J, Salloway S, Xiong C, Benzinger T, Buckles V, Masters CL, Sperling R, Bateman RJ, Morris JC, Laske C . Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Sept. 25, 2018, In Press

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  1. The paper by Mueller et al. demonstrates for the first time the existence of an association between self-reported physical activity and cognitive status even in patients with Alzheimer’s disease of genetic origin. The paper is interesting and well-conducted, with multiple measures of outcome (cognitive performance, functional status and CSF biomarkers).

    The main limitation of the study, as acknowledged by the authors, is its cross-sectional nature, which only allows the demonstration of associations, but not of cause-effect relationships. After reading this paper, one would still like to know whether a high level of physical activity does improve cognitive status or, vice versa, whether the patients with cognitive deficit are prone to perform less physical activity.

    Still, this paper favors the idea that physical activity may be considered an important therapeutic tool in patients at risk of cognitive decline, including those with autosomal dominant AD.

    View all comments by Antonio Muscari

  2. The paper is interesting and is consistent with a lot of other research that seems to indicate a protective association between exercise and the risk of AD, dementia, and cognitive performance.

    It's a bit different in that the population involves people with a risk of a rare form of genetic AD that predominantly effects younger people.  It's also cross-sectional—and add to that what seems like those people in the mutation carrier group for some reason had higher levels of exercise. Overall, to have 70 percent of any group reporting 150 minutes of physical activity per week indicates to me this is not a typical population.

    But the authors’ point that they are the "first to support a beneficial effect of PA ... in genetically driven autosomal-dominant AD" is interesting. The more interesting results will be when they can report longitudinal data and have endpoints that are not based on estimated year to onset (EYO).  

    View all comments by Eric Larson

  3. The article by Müller and colleagues provides compelling cross-sectional data on the relationship between physical activity, cognition, functional ability, and Alzheimer’s disease biomarkers in an autosomal-dominant AD population. As the authors stated, it will be important to examine this longitudinally. Although we are not collecting information on physical activity in the Alzheimer’s Prevention Initiative (API) Autosomal-Dominant AD trial, we have the possibility of doing so in the API Colombia Registry and API BIO cohorts. Our colleagues at the University of Antioquia and Massachusetts General Hospital are collecting information on physical activity as part of the observational biomarker study with the Colombian kindred and with plans to examine the impact of physical activity on cognitive decline and brain dysfunction, including on AD biomarker measures.

    View all comments by Jessica Langbaum

  4. Since most people do not get sufficient exercise, it would be interesting to determine if exercise-induced changes in expression levels of antioxidant enzymes such as glutathione-S transferase play a role in the protection observed in this study. Such studies could be performed relatively quickly in rodent models.

    View all comments by Marcia Ratner

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