Alzheimer’s Disease

It’s well established that having a parent or sibling with Alzheimer’s increases a person’s risk of developing the disease. A new, NIA-supported study shows that even in the absence of close family members with Alzheimer’s, having extended family members with the disease increased a person’s risk. The findings, published April 9 in Neurology, could have implications for assessing risk using a broader view of family history.

A team of researchers from the University of Utah School of Medicine, Huntsman Cancer Institute, George E. Wahlen Department of Veterans Affairs Medical Center, Utah State University, and Brigham Young University mined the Utah Population Database. This record of Utah founders from the 1800s and their descendants, was used to identify individuals with genealogy data for at least 12 ancestors in the last three generations. The resulting pool of more than 270,000 individuals included 4,436 with Alzheimer’s as the primary or contributing cause of death.

To measure relative risk, the researchers compared the actual number of people who had Alzheimer’s with the expected number of Alzheimer’s cases based on various family histories of the disease. The analysis included first-degree relatives (parents, children, and siblings), second-degree relatives (grandparents, grandchildren, aunts and uncles, and nieces and nephews), and third-degree relatives (great-grandparents, great-grandchildren, grand nieces, grand nephews, great aunts and uncles, and first cousins).

In line with previous studies, the researchers found that having one or more first-degree relatives with Alzheimer’s put people at significantly higher risk for the disease. People with one first-degree relative with Alzheimer’s were 1.73 times more likely to develop the disease. Looking further into the family tree, people with two first-degree relatives with Alzheimer’s were nearly four times more likely to develop the disease. Those with three first-degree relatives were nearly two-and-half more times likely, and those with four were almost 15 times more likely to develop Alzheimer’s disease.

But even people whose parents or siblings did not have Alzheimer’s were at higher risk in most cases if they had second- or third-degree relatives with the disease, the researchers found. For example, people with three or four second-degree relatives who had Alzheimer’s were more than twice as likely to develop the disease. People who had only third-degree relatives with Alzheimer’s had a 43 percent increased risk when they had three or more such relatives with the disease.

People at the lowest risk had no relatives with Alzheimer’s disease or only one or two third-degree relatives with Alzheimer’s.

A family history of Alzheimer’s does not mean that a person will develop the disease, and a lower risk does not mean a person won’t get the disease. Rather, an individualized assessment of risk based on one’s extended-family history might help identify people who may benefit from monitoring for early signs of disease and steps that might help prevent dementia, the authors wrote.

It’s important to note that estimates in this study are based on the Utah study population and may not apply to other populations. The study also did not incorporate genetic influences or other risk factors into the calculations of relative risk, which is an area the researchers are now beginning to explore.

This study was supported by NIA grant RF1AG054052.

Reference: Cannon-Albright LA, et al. Relative risk for Alzheimer disease based on complete family history. Neurology. 2019;92(15):e1745-e1753.

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