We know that having a parent with Alzheimer’s disease or inheriting the ApoE4 gene puts a person at a higher risk for Alzheimer’s. Now, a new study shows that the genetic link goes deeper: Having a great-grandparent or a cousin puts people at a higher risk for Alzheimer’s, too.
In a report published in the journal Neurology, researchers from the University of Utah School of Medicine in Salt Lake City found that a second- or third-degree relative could raise the risk of Alzheimer’s—and the closer the relative, the higher the risk.
“Family history is an important indicator of risk for Alzheimer’s disease, but most research focuses on dementia in immediate family members, so our study sought to look at the bigger family picture,” said study author Lisa A. Cannon-Albright, Ph.D., of the University of Utah School of Medicine in Salt Lake City. “We found that having a broader view of family history may help better predict risk. These results potentially could lead to better diagnoses and help patients and their families in making health-related decisions.”
Researchers used the Utah Population Database, which includes data going back to the 1800s from Utah pioneers and their modern-day relatives. Death certificates are linked to the data, so researchers were able to narrow down people who died of Alzheimer’s disease or had it listed as a contributing cause of death. They looked at 270,800 people who could be traced through the prior three generations with data from both parents, all four grandparents and a minimum of six of eight great-grandparents.
Of that data set, 4,436 listed Alzheimer’s on the death certificate. When researchers examined the descendants of people with Alzheimer’s, they found that people with a first-degree relative—a parent or sibling—had a 73 percent increased risk of Alzheimer’s, meaning they are 1.73 times as likely to develop the disease as someone with a family history of Alzheimer’s.
When a person had two first-degree relatives with Alzheimer’s, their risk shot up much more—to 398 percent, or 4 times as likely to develop the disease as someone with no family history. Those with four affected relatives were 15 times more likely to develop the disease.
The risk was low for people who had one or two second-degree relatives with Alzheimer’s—aunts and uncles, grandparents or a sibling who shares one parent—but increased when the number of second-degree relatives with Alzheimer’s rose to three. Those people were 2.46 more likely to get Alzheimer’s than someone without a family history.
The greatest risk was found for people who have one first-degree relative and two second-degree relatives with Alzheimer’s, rising to 21.29 times more likely to develop Alzheimer’s than someone with no family history.
“More and more, people are increasingly seeking an estimate of their own genetic risk for Alzheimer’s disease,” said Cannon-Albright. “Our findings indicate the importance of clinicians taking a person’s full family history that extends beyond their immediate family members.”
Still, the study has limitations. Alzheimer’s is often misdiagnosed and under-diagnosed, research suggests, especially in decades past. It could be that Alzheimer’s was listed as a cause of death for some people who did not have the disease, and was not listed for those who did.
“There are still many unknowns about why a person develops Alzheimer’s disease,” said Cannon-Albright. “A family history of the disease is not the only possible cause. There may be environmental causes, or both. There is still much more research needed before we can give people a more accurate prediction of their risk of the disease.”
A family history of Alzheimer’s does not, by any means, guarantee that a person will get the disease.
“Although this study does suggest that a family history, including extended family such as great-grandparents, is linked to an increased—it doesn’t mean people with a family history will definitely go on to develop dementia, said James Pickett, Ph.D., of the Alzheimer’s Society. “Alzheimer’s risk is complex, with many factors at play. By following good lifestyle advice, even people with a strong family history could significantly reduce their risk.”