Conjugal Alzheimer disease: risk in children when both parents have Alzheimer disease
Jayadev S, Steinbart EJ, Chi YY, Kukull WA, Schellenberg GD, Bird TD;
Commented by , 31 Mar 2008
Aim of the study
To determine the risk of Alzheimer's disease (AD) in families where both parents have AD.
Method
Retrospective analysis from the University of Washington AD Research Center registry. AD was diagnosed using NINCDS-ADRDA criteria. Survival analysis of risk was performed using a non-parametric Kaplan-Meyer estimate to draw the cumulative risk curves.
Results
111 couples with AD were found, mean age at onset of 74.5 years for 174 subjects, 48/222 with autopsy-confirmation. They had 297 children surviving to adulthood, and 22.6% of these adult children have developed AD at the time of ascertainment, with a mean age of onset of 66.3 years.
The risk of AD was found to increase with age 31.0% (58 of 187) over age 60, 41.8% (41 of 98) over age 70. Many of the children are still below age 70. A family history of AD beyond the two parents did not change the risk of AD in the children but reduced the median age of onset in affected children (72 years if no family history beyond the parents, 60 years if for one parent, 57 years if both parents). ApoE genotype was available only in 17 children with AD, 7 carrying apoE4/4, 8 apoE3/4, 2 apoE3/3.
Professor Gauthier's comments
The authors conclude that when both parents have AD, the risk for their adult children is higher than that of the general population. ApoE4 plays an important role in this phenomenon but did not explain all cases of AD in the children, supporting a complex polygenic phenomenon.
It is not unusual for health middle-life individuals to consults memory clinics to estimate their level of risk towards AD. This study provides useful information in this regard. Unfortunately for now no specific preventive treatment can be offered to these subjects, but they could be enrolled in a prospective cohort of persons at higher risk who would be offered participation in intervention studies.
Furthermore studies of the type recently published in the same journal (ref. 1) using genomewide association analysis could be done in such a cohort.
References
1. Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, et al. Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Archives of Neurology 2008; 65 (1); 45-53. [Epub 2007 Nov 12]