Targeting the Milieu in Neurodegenerative Disease: Time for “Imprecision Medicine”?

The possibility of developing precision therapies for neurodegenerative disease is tantalizing, and efforts are under way with several diseases, including Alzheimer's, Parkinson's and Huntington's disease. Despite strong basic neuroscience foundations and excellent clinical trial design, however, these efforts have been disappointing. We present an argument for a complementary approach of targeting the brain milieu in order to achieve disease-modifying effects in patients with or at risk of neurodegenerative disease. We suggest that a milieu-directed "brain health" approach can be applied across a range of at-risk individuals in a specific, quantitative, evidence-based manner. In support of this position, we present data from epidemiologic studies and clinical trials. We propose a program of rigorous research to validate and implement this complement to precision medicine which skeptics might call "imprecision medicine."