"We and other investigators have found evidence that estrogen helps protect women from developing Parkinson's," says Walter Rocca, M.D., M.P.H., Mayo Clinic neurologist and epidemiologist, and lead study investigator. "So, a gene variant that would decrease estrogen production or activity would put those women at greater risk for the disease."

The study associated variants in the following three genes with development of Parkinson's: estrogen receptor 1 gene (ESR1); estrogen receptor 2 gene (ESR2); and PR domain-containing protein 2 gene (PRDM2).

"The gene variants are not a defect or a problem in and of themselves -- they are part of human differences, simply differences across people, like being slim, short or blue-eyed," says Dr. Rocca. "These differences make one subgroup of the population more susceptible to a disease like Parkinson's. However, sometimes the genetic variant is a weak risk factor, and the disease only manifests if another risk factor is present, such as a particular diet, physical exercise, taking certain medications or a medical event."

The study was conducted using a database from a previous study of the entire human genome for genes linked to Parkinson's. For the new study, the Mayo Clinic investigators examined several genes for variants in 172 women who had Parkinson's and 229 women who did not have the disease.

Dr. Rocca explains that some genetic variants the study pinpointed for association with Parkinson's are quite common, affecting 10 to 20 percent of the female population. As women are not routinely tested for these gene variations, however, those affected would be unaware, he says.

"If the findings of this study are replicated and confirmed, the hope is to use these variants to predict the risk of disease using a simple blood test," says Dr. Rocca. He explains that the test would be particularly useful for women and their physicians before deciding to conduct an elective ovariectomy, surgical removal of the ovaries, because a combination of estrogen-reducing factors could amplify a woman's risk for Parkinson's.

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At the beginning of the study, 7.6 percent of patients had a history of stroke. All participants experienced a decline in memory over time, but the decline was more rapid in those patients with a history of stroke. The association was stronger in men and individuals without a particular type of gene known as an APOEe4 allele, which has been linked to Alzheimer's disease in previous research. Abstract/visuospatial abilities, which do not involve language, also declined among men and those without the APOEe4 allele who also had a history of stroke.

"The mechanisms by which stroke increases the risk of cognitive decline are not clear," the authors write. Stroke may increase the risk of memory problems by destroying or damaging certain areas of the brain or by triggering the deposit of materials that form the hallmark brain plaques associated with Alzheimer's disease. "It is also possible that the occurrence of stroke adds cognitive deficits in person with subclinical Alzheimer's disease that bring them over the diagnostic threshold  and that stroke does not have a direct specific effect on Alzheimer's disease."

"A history of stroke is related to a progressive decline in memory and abstract/visuospatial performance, especially among men and those without an APOEe4 allele," they conclude.

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