Dementia becomes more common with age, with a prevalence of 5 percent to 10 percent in people over age 65 and 20 percent in people over age 80. It is difficult to distinguish even the three most common types of dementia: Alzheimers disease, Lewy body disease and multi-infarct dementia. Alzheimer's, the most common form of dementia, is genetically complex. To date, mutations in three genes (APP, PSEN1, and PSEN2) have been identified as causes of familial early-onset Alzheimer's. In addition, a change in the apolipoprotein E (APOE) gene has been associated with the more common late-onset form of the disease. These four genes account for less than 30 percent of the genetic variance in age of onset for Alzheimer's disease. Numerous other genes that influence Alzheimer's risk may exist.

Another type of dementia, caused by Lewy body disease, accounts for 20 percent of all cases of dementia in old age. It can be associated with mutations in the alpha synuclein gene, but most Lewy body dementia is not. The ability to identify underlying genetic influences that result in different synuclein pathologies is key to understanding these disorders.

Investigators hope to gain a better understanding of the biochemical and physiological processes and complex genetic interactions underlying the diseases that cause dementia. Their first aim is to identify families with a history of dementia in an attempt to clone the causative gene defect(s). Their second aim is to investigate the association between genetic polymorphisms and dementia. This will be performed by a candidate gene approach, assessing the contribution of genes already associated with familial forms of disease, likely candidates, or genes within a genetic region previously linked to disease.