Knopman, David S.

There are many who feel that the achievement of a disease‐modifying (DM) designation for a drug is an important goal in Alzheimer disease (AD) therapeutics. Several designs that might prove DM have been proposed, including randomized start, randomized withdrawal, and slope analysis. Using biomarkers such as cerebrospinal fluid assays or imaging features as primary outcome measures have also been considered a way of proving DM. The available methods for establishing DM are fraught with logistical and analytic problems. Unless the drug's benefits are large, attempts to prove DM for a truly effective drug may fail. Therefore, clinical trial designs that are the simplest to conduct and interpret are superior to those more complex approaches intended to prove DM.

AbstractBackgroundThe Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health.MethodsCriteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience.ResultsNinety‐six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes.ConclusionThis review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.