The Health Outcome

Cognitive impairment in the elderly is a serious public health problem because it is fairly prevalent in older persons (15% of persons over age 65 years suffer from dementia (1)) and it increases the risk for a number of adverse health outcomes, including hospitalization, nursing home admission, and death. Investigators have reported that the ε4 allele of the APOE gene is associated with an increased risk for cognitive impairment. In addition, elevated systolic blood pressure (SBP) is associated with an increased risk of cognitive impairment. The authors of this study speculated that an interaction might exist between the ε4 allele of the APOE gene and elevated SBP on the risk of cognitive impairment (2).

The Finding

This cohort study was based on a sample of 3,605 Japanese-American men. Investigators measured SBP at three time points during midlife, and then measured cognitive function at late-life. Genotyping on blood samples obtained from participants allowed for identification of the presence or absence of the ε4 allele of the APOE gene.  The investigators divided the sample into four groups:  1) normal SBP (< 160 mmHg)/No ε4 , 2) normal SBP/ ε4, 3) high SBP (≥ 160 mmHg)/ No ε4, and 4) high SBP/ ε4.  The relative odds of developing poor cognitive impairment in these four groups was 1.00 (reference), 1.3, 1.8, and 2.9 respectively, suggesting a possible interaction between high SBP and the ε4 allele, but the interaction was not statistically significant (p = .62).  In further analyses, the authors found stronger evidence of a high SBP, ε4 interaction among those never treated with antihypertensive medications, suggesting a possible three-way interaction between high SBP, ε4, and lack of antihypertensive medication use.  Among those never treated with anithypertensive medications, the relative odds of poor cognitive function for the four SBP/ε4 groups noted above was 1.0, 1.3, 2.4, and 10.8, respectively.  However, a three-way interaction term for high SBP, ε4, and antihypertensive medication use was only marginally significant (p = .09) (2-3).

Public Health Implications

This study provides some evidence persons who have elevated SBP and at least one copy of the APOE ε4 allele could be at particularly high risk for late-life cognitive impairment, especially if they are not treated with antihypertensive medications.  Thus, treating such persons with antihypertensive medications and monitoring their cognitive status closely over time may be needed.  The interactions reported by the authors were suggestive but not statistically significant, so further research on the interaction between high SBP and APOE ε4 is needed.  Additionally, because the study population was restricted to Japanese-American men, the applicability of the study results to other groups of persons is not clear.

References

1. Larson EB, Kukull WA , Katzman RL. Cognitive impairment:  dementia and Alzheimer’s disease.  Annu Rev Public Health  1992;13:431-49.
2. Peila R, White LR, Petrovich H, et al.  Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment.  Stroke  2001; 32(12):2882-9.
3. E-journal club abstraction template