By Linda Carroll

(Reuters Health) – Having second- or third-degree relatives with Alzheimer’s raises a person’s risk of developing the disease, a new study suggests.

It’s already known that children of Alzheimer’s patients are at higher risk for the disease. But in the new study, people with Alzheimer’s in their extended family were also at a higher risk of the disease compared to those with no family history, researchers report in Neurology.

The more closely related the relatives with Alzheimer’s, and the greater their number, the higher an individual’s risk of developing the disease.

“The big picture message is that this reiterates how important and powerful (both close and distant) family history can be for risk prediction,” said the study’s lead author, Lisa Cannon-Albright of the University of Utah School of Medicine in Salt Lake City.

The new study was possible only because Cannon-Albright and her colleagues were able to tap into a very complete genealogy, the Utah Population Database, which includes information on families dating back to the original pioneers who settled the state in the 1800s. The family histories are linked to Utah death certificates, which show not only a cause of death, but also other contributing causes in the majority of cases.

From that database, the researchers selected 270,080 people who had at least three generations of genealogy with data for both parents, all four grandparents and at least six of eight great-grandparents. Among them were 4,436 people with a death certificate that indicated Alzheimer’s disease as a cause of death.

People who had one first-degree relative with Alzheimer’s – a parent or a full sibling – were 1.73 times as likely as those with no family history to develop the disease themselves. Two or more first-degree relatives had a much bigger impact: people in this category were 3.98 times as likely as those without a family history of the disease to develop Alzheimer’s.

Having just one or two affected second-degree relatives – grandparents, blood-related aunts and uncles, and siblings who shared just one parent – but no affected first-degree relatives had a small impact on risk. But things changed dramatically with three or more affected second-degree relatives. In that case, the risk of developing Alzheimer’s rose to 2.46 times that of someone with no family history.

The risk really shot up for people with one affected first-degree relative and two affected second-degree relatives: they were 21.29 times more likely to develop Alzheimer’s compared to people with no family history.

One might feel safe having no first- or second-degree relatives with Alzheimer’s, but the researchers found that people with a history of Alzheimer’s in three or more third-degree relatives – great-grandparents, great-uncles and -aunts and first cousins – were 1.43 times as likely as those with no family history to develop the disease.

“The increased risk (in those with just third-degree relatives) illustrates the strong role of inherited predisposition in Alzheimer’s,” Cannon-Albright said in an email. “It’s likely the genes these relatives share are responsible for their predisposition to Alzheimer’s. So even in the situation where someone doesn’t have any close relatives affected, they are still likely sharing the predisposing gene factors.”

The new study confirms how important it is to take a detailed family history, said Weiyi Mu, a genetic counselor in the Institute of Genetic Medicine at Johns Hopkins University in Baltimore. “Alzheimer’s disease is a multifactorial disorder,” she said.

“Typically we rely on studies like this one. I was very happy to see a study with second and third generations included. This is a valuable addition to the body of literature we use to talk to people about risk,” Mu said. “It makes me think there’s a lot more data out there in genealogical records that we could use to look at other diseases.”

SOURCE: Neurology, online March 13, 2019.