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2011 Grants - Sherva
Genetics of Rate of Cognitive Decline in a Clinical Trial of Alzheimer's Disease
Richard Sherva, Ph.D., M.P.H.
2011 New Investigator Research Grant
Alzheimer's disease is a progressive neurological disorder. Most people with the disease tend to experience declines in cognition and executive function (or the ability to carry out daily tasks). But the rate of decline often varies greatly from one individual to another. The reasons for this heterogeneity of decline in Alzheimer's are unknown, but they may involve genetic factors that could reveal important information about the processes behind dementia.
In preliminary research, Richard Sherva, Ph.D., M.P.H., and colleagues analyzed cognitive and genetic data from a small group of elderly people with dementia. Using complex statistical methods, they identified certain segments of DNA (a component in cells that contains the specific genetic information needed for any living organism to develop and function) called single nucleotide polymorphisms (SNPs) that were associated with a particular rate of cognitive decline. Similar results were also achieved in a study of people with Alzheimer's disease at the Religious Orders Study and Rush Memory and Aging Project.
For their current effort, Dr. Sherva and colleagues expect to confirm their earlier results using data from elderly participants in an ongoing clinical trial. The researchers will focus on 96 individual SNPs in 56 genes. They will assess whether these SNPs are associated with the participants' rates of decline as measured by several tests of cognition and function. The team will focus on identifying particular chromosomes that harbor the SNPs most closely associated with dementia progression rates. Such research could lead to targeted therapies aimed at slowing cognitive and functional decline in Alzheimer's disease.