Children have an increased risk for Alzheimer's disease in adulthood if both parents have the disorder, reported researchers in the March Archives of Neurology. Family history of the disease also appeared to mediate age at onset but not the overall risk in this cohort of children of couples with Alzheimer's disease. In addition, although presence of the apolipoprotein E (APOE) ε4 allele appeared to play an important role in this phenomenon, it was not the sole cause of all cases of Alzheimer's disease, said Suman Jayadev, MD, Acting Assistant Professor of Neurology at the University of Washington in Seattle, and coauthors.
Affected Spouses Boost Risk in Offspring
A total of 111 couples with probable or definite Alzheimer’s disease were identified from the University of Washington Alzheimer’s Disease Research Center registry; mean age of dementia onset was 74.5. Of the 297 children who survived to adulthood, 67 (22.6%) had a clinical diagnosis of Alzheimer’s disease at the time of the study. However, because nearly 80% of the unaffected offspring had not yet reached age 70, Dr. Jayadev and colleagues suggested that the overall prevalence of Alzheimer’s disease in this population is likely an underestimation.
“Of the 223 living offspring, the mean age was 62 years, showing that many of the children have not yet reached the ages having the highest risk of Alzheimer’s disease,” the researchers said. About one-quarter of the offspring 50 or older had a diagnosis of Alzheimer’s disease, and the prevalence rate increased to 31% in offspring 60 or older, to 35.7% in those 65 or older, and to 41.8% in those 70 or older. Cumulative risk for Alzheimer’s disease by age 70 was approximately 20% and increased to above 60% at age 80. “It is therefore probable that the prevalence of Alzheimer’s disease in this study group will be even higher once more offspring have lived beyond age 70 years,” asserted the authors.
The mean age at onset was younger among fathers and male offspring (73.9 and 64.7, respectively) than among mothers and female offspring (75.1 and 67.6, respectively). For offspring 70 and older, however, the researchers observed a nonsignificant trend toward increased risk for Alzheimer’s disease in women.
Family History, APOE, and Risk for Alzheimer’s Disease
A review of medical records indicated that 152 offspring had a confirmed family history positive for Alzheimer’s disease beyond their parents, and 106 had a confirmed family history negative for Alzheimer’s disease. Diagnoses of dementia were established in 14.5% and 21.7% of the two groups, respectively, although the difference was not statistically significant. Rates of Alzheimer’s disease incidence were also not significantly different between subgroups with a negative family history, unilateral family history, or bilateral family history.
“Although the presence of Alzheimer’s disease did not seem to be affected by the presence of a family history, age at onset of Alzheimer’s disease correlated with a positive family history,” stated Dr. Jayadev and colleagues. Offspring with a family history negative for Alzheimer’s disease had an older median age at onset than those who had one parent with a family history of Alzheimer’s disease (72 vs 60). Children who had a positive family history on both parents’ sides had the youngest median age at onset (57). However, the researchers noted that families with a significant disease history may be more likely to be referred to an Alzheimer’s disease research center, which may have led to a selection bias for a “particularly Alzheimer’s disease–prone” subgroup.
Although there were only 17 APOE genotypes in the sample, “it was clear that the ε4 allele was overrepresented in the affected offspring,” said the researchers. However, they noted that the genotype did not fully account for the increased risk, which supports the likelihood of additional genetic factors.
—Jessica Dziedzic