Danielle Wilson, R. Peters, K. Ritchie
May 1, 2011
Therapeutic Advances in Chronic Disease
Objectives: In this paper we aim to: (1) identify and review midlife risk factors that may contribute to the development of dementia and that may be amenable to intervention; (2) review advances made in our understanding of the most common cause of dementia, Alzheimer’s disease (AD), where current pharmacological studies have aimed to modify the disease course; and (3) explore other interventions that may slow cognitive decline in those with AD. Methods: A review of the literature was conducted to look for interventions that may modify the risk of incident dementia or that may modify symptom progression in those with diagnosed dementia. Results: (1) Midlife risks identified as amenable to intervention include blood pressure, diabetes, elevated cholesterol, poor psychosocial and lifestyle factors. (2) The leading drugs in development can be grouped by their principal target: anti-amyloid, anti-tau and mitochondrial stability. However to date, there have been no successes in late stage Phase III trials of putative disease-modifying drugs for AD. (3) Once the diagnosis of dementia has been made there is little that can slow the rate of decline. Possible exceptions include the use of exercise and antihypertensive medication with some nootropic medication showing promise in small trials. Conclusion: (1) It is clear that there are several risk factors in midlife that may lead to a greater likelihood of developing dementia. However, there is no simple intervention to modify these risks. It seems sensible to conclude from the data that avoiding high blood pressure, controlling cholesterol and diabetes as well as maintaining a healthy diet and lifestyle may lower the risk of developing dementia. (2) The need for better outcome measures in clinical trials is evident and may, in part, explain the numerous failures in late-stage clinical trials of disease-modifying drugs. Improved diagnostic test batteries to reduce population heterogeneity in early intervention studies will be required for robust clinical trials in the future. (3) Current research indicates that there is little that can delay decline; however, future trials may wish to focus on nootropics.