Challenges in clinical research on Alzheimer's disease: Leon Thal's legacy

Abstract

First and foremost, Leon Thal was a clinician. While he was an expert in clinical trials and a superb basic scientist, he was primarily a clinical neurologist. As such, Leon had a real appreciation for clinical diagnoses and the implications of them for patients and families.Leon was keenly aware of the importance or moving the diagnostic threshold for Alzheimer's disease (AD) to earlier stages, since it was his belief that, if truly disease-modifying therapies were to be beneficial, they would need to be instituted at an early point in the disease process. This ultimately would have implications for treating asymptomatic individuals.Leon was an early proponent of the concept of mild cognitive impairment (MCI) as a means of identifying individuals at high risk for developing clinical AD at an earlier point in the clinical spectrum. He recognized MCI as the next step for improving our clinical acumen to identify individuals who were going to develop the full picture of AD. Hence, he endorsed and supported the first clinical trial designed to investigate the utility of therapeutics prior to the clinical diagnosis of AD [1].