The Health Outcome

Alzheimer's disease (AD) is a common neurogenerative disorder in the elderly population. It is characterized by progressive dementia, beginning with memory loss and ending in death. Early-onset AD (before age 65) occurs in 1-2% of cases. Approximately 40-60% of AD cases have a positive family history of dementia. The ε4 allele of the apolipoprotein E ( APOE ) gene is a risk factor for both early-onset and late-onset AD. Other hypotheses suggest that genetic or environmental factors may interact with APOE to cause AD. Other genes studied in relation to AD include NOS3, PSEN1, and beta-APP.

The Finding

In a cohort of 1,869 Japanese Americans followed for an average of 3.8 years, 59 incident cases of probable AD were identified. On average, cases were slightly older than noncases at entry (79.2 years vs. 71.9 years) and more were female (61% vs. 55.6%). Pearson correlation coefficients were calculated for the independent variables. There was a meaningful and statistically significant correlation between head circumference (HC) and sex, height and sex, HC and height, and HC and body mass index (BMI). In a Cox proportional hazards model, APOEε4 was found to be a significant predictor of AD in women, controlling for education and HC (hazard ratio [HR] = 5.57, 95% conficence interval [CI] = 1.64-18.85, p=0.006). The HR for incident AD associated with having both HC in the lowest tertile and having an APOE ε4 allele, adjusted for BMI and education, was significant for both men and women. The HR for females was 14.37 (95% CI=2.05-100.7, p=0.007) and the HR for males was 69.19 (95% CI = 4.42-1082, p=0.003). A multiplicative interaction effect was observed between HC and APOEε4 status.

Public Health Implications

The authors state in their discussion “If one considers HC in the lowest tertile to be an ‘enabling causal factor,' one can speculate what proportion of the disease could be prevented if one could boost brain reserve throughout the lifecycle. From our study, the attributable risk percent explained by HC in the lowest tertile is 18.2%; thus, almost one-fifth of the disease among individuals with small HC might be preventable.” If the amount of “brain reserve” a person has is based on the maximal-attained size of their brain, it is hard to imagine what intervention would be recommended (to increase brain size). A person's brain normally attains its maximal size in early childhood. The authors suggest that involvement in enrichment activities such as mental exercises could delay the onset of AD. However, it is not clear that these activities have any effect on increasing or maintaining a person's brain size. The results of this study have little public health implication because a person can do nothing to change their head size or their APOE status

References

1. Borenstein Graves A, Mortimer JA, Bowen JD, et al. Head circumference and incident Alzheimer's disease: modification by apolipoprotien E. Neurology 2001;57(8):1453-60.
2. Borenstein Graves A. et al. e-Journal abstract