Comment
“who, what, and when” to intervene. Methods will be developed to enable investigators to use these cohorts in conjunction with—or embedded in—trials, as will approaches that could create virtual life-course cohorts and interventions that link existing studies to one another. Initiatives have been started to pool data and to use hypothesis-driven and agnostic data mining and systems biology approaches.3,4 Innovative short-term physiological or functional challenge interventions are needed to ascertain whether or not an intervention can potentially change the target pathway in a short period. Finally, despite the overall disappointing results of previous trials, we should not throw the baby out with the bathwater. Many interventions are promising, but they might have been tested in the wrong population subgroup or with the wrong formulation. To this end, improvement in the standards of Alzheimer’s disease prevention trials is crucial. Many trials so far have been underpowered and under-reported, and the development of standards of trial implementation and analysis, in addition to reporting and sharing of data, will certainly help the specialty to move forward. Furthermore, we can draw many more lessons from the trials if we plan for
failure and add, in anticipation, measures that could help us to understand better why a trial fails. In summary, prevention of Alzheimer’s disease will be difficult, but the pathway forwards will become clearer as we gain a better understanding of the heterogeneity in the pathways that lead to a common dementia phenotype, the need for interventions targeting different trajectories, and the need for improved standardised methods to use in future trials. Lenore J Launer Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA [email protected] I declare no competing interests. 1
2 3
4
Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer’s disease: lessons learned from clinical trials and future directions. Lancet Neurol 2015; published online July 24. http://dx.doi. org/10.1016/S1474-4422(15)00153-2. Launer LJ. The epidemiologic study of dementia: a life-long quest? Neurobiol Aging 2005; 26: 335–40. National Institutes of Health. Accelerating Medicines Partnership. Alzheimer’s disease. http://www.nih.gov/science/amp/alzheimers.htm (accessed July 28, 2015). Medical Research Council. Dementias Platform UK. http://www.mrc.ac.uk/ research/facilities/dementias-platform-uk/ (accessed July 28, 2015).
Corrections Fugate JE, Rabistein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14: 914–25—The Acknowledgments section of this Review (published online on July 14, 2015) should instead read “Contributors.” This correction has been made to the online version as of August 10, 2015, and the printed version is correct.
874
www.thelancet.com/neurology Vol 14 September 2015
“who, what, and when” to intervene. Methods will be developed to enable investigators to use these cohorts in conjunction with—or embedded in—trials, as will approaches that could create virtual life-course cohorts and interventions that link existing studies to one another. Initiatives have been started to pool data and to use hypothesis-driven and agnostic data mining and systems biology approaches.3,4 Innovative short-term physiological or functional challenge interventions are needed to ascertain whether or not an intervention can potentially change the target pathway in a short period. Finally, despite the overall disappointing results of previous trials, we should not throw the baby out with the bathwater. Many interventions are promising, but they might have been tested in the wrong population subgroup or with the wrong formulation. To this end, improvement in the standards of Alzheimer’s disease prevention trials is crucial. Many trials so far have been underpowered and under-reported, and the development of standards of trial implementation and analysis, in addition to reporting and sharing of data, will certainly help the specialty to move forward. Furthermore, we can draw many more lessons from the trials if we plan for
failure and add, in anticipation, measures that could help us to understand better why a trial fails. In summary, prevention of Alzheimer’s disease will be difficult, but the pathway forwards will become clearer as we gain a better understanding of the heterogeneity in the pathways that lead to a common dementia phenotype, the need for interventions targeting different trajectories, and the need for improved standardised methods to use in future trials. Lenore J Launer Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA [email protected] I declare no competing interests. 1
2 3
4
Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer’s disease: lessons learned from clinical trials and future directions. Lancet Neurol 2015; published online July 24. http://dx.doi. org/10.1016/S1474-4422(15)00153-2. Launer LJ. The epidemiologic study of dementia: a life-long quest? Neurobiol Aging 2005; 26: 335–40. National Institutes of Health. Accelerating Medicines Partnership. Alzheimer’s disease. http://www.nih.gov/science/amp/alzheimers.htm (accessed July 28, 2015). Medical Research Council. Dementias Platform UK. http://www.mrc.ac.uk/ research/facilities/dementias-platform-uk/ (accessed July 28, 2015).
Corrections Fugate JE, Rabistein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14: 914–25—The Acknowledgments section of this Review (published online on July 14, 2015) should instead read “Contributors.” This correction has been made to the online version as of August 10, 2015, and the printed version is correct.
874
www.thelancet.com/neurology Vol 14 September 2015
