The risk doubled if a person had both a first-degree relative (parent or sibling) and a second-degree relative (grandparent, aunt, uncle, or a sibling who shared one parent) who had the disease, according to Lisa Cannon-Albright, PhD, of the University of Utah in Salt Lake City, and colleagues.
“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,” Cannon-Albright said in a statement.
“We found that having a broader view of family history may help better predict risk,” she added. “These results potentially could lead to better diagnoses and help patients and their families in making health-related decisions.”
For this study, the researchers used the Utah Population Database, a record of Utahans from the 1800s and their descendants linked to death certificates from 1904 to 2014, to estimate relative risk for Alzheimer‘s disease based on specific family history.
Death certificates included primary cause of death, and contributing causes of death also were available for the majority of linked death certificates. Because Alzheimer‘s disease first appeared as a coded cause of death in ICD-9, only death certificates coded with ICD-9 or ICD-10 were included.
The analysis included 270,818 people with genealogy data for at least 12 immediate ancestors and a linked Utah death certificate; more than half of these individuals died after 1978. Of those people, 4,436 had a Utah death certificate that indicated Alzheimer‘s disease as a primary or contributing cause of death, with most of those deaths (3,298) occurring after 2000. The majority of Alzheimer‘s deaths were in women (64%) and the median age of death was 85.
The analysis showed that having any first-degree relative with Alzheimer‘s significantly increased risk:
- ≥1 first-degree relative: RR 1.73 (95% CI 1.59–1.87)
- ≥2 first-degree relatives:RR 3.98 (95% CI 3.26–4.82)
- ≥3 first-degree relatives: RR 2.48 (95% CI 1.07–4.89)
- ≥4 first-degree relatives: RR 14.77 (95% CI 5.42–32.15)
Having a second-degree relative and two first-degree relatives with Alzheimer‘s increased risk by 21 times (RR 21.29; 95% CI 5.80–54.52).
Alzheimer‘s disease in only third-degree relatives also upped risk: a person who had no first- or second-degree relatives with Alzheimer‘s, but had three or more third-degree relatives with the disease, had a relative risk of 1.43 (95% CI, 1.21–1.68).
The results suggested that given an equivalent family history, men were at higher risk for Alzheimer‘s disease than women. Evidence was mixed about differences on maternal versus paternal inheritance.
Specific family history constellations showed “that second-degree and third-degree family history, even in the absence of first-degree family history, can be indicative of significantly elevated risk,” Cannon-Albright and co-authors wrote. “These findings indicate the importance of a full family history that extends beyond immediate family members.”
This analysis has several limitations, the researchers said. Cases of Alzheimer‘s disease may have been missed: people with Alzheimer‘s may not have had the disease listed as a cause of death. People who died before ICD-9 coding was implemented were eliminated from the study, as were people who did not have death records linked to genealogy data. In addition, the Utah study population is unique and results may not apply to others.
The researchers reported relationships with June Morris Trust, Rodney and Carolyn Brady Fund, GE Health, AbbVie, Biogen, Lilly Pharmaceuticals, and Proactive Memory Services, Inc.