APOE genotype modulates the effect of serum calcium levels on cognitive function in old age

Objective: The APOE genotype and serum calcium levels have both been associated with cognitive impairment. Animal studies have shown variation in apoE isoforms to play a critical role in intraneuronal calcium homeostasis, but the contribution of this interaction to cognitive function in man is unknown. Here, we studied whether the APOE genotype modulates the association between serum calcium levels and cognition. Methods: Within the Leiden 85-plus Study, a prospective population-based study of 599 subjects aged 85 years, we measured serum calcium levels and APOE genotype at baseline. During a 5-year follow-up period, cognitive function was annually assessed using the Mini-Mental State Examination (MMSE) and a standardized neuropsychological test battery. Results: Both at baseline and during follow-up, high serum calcium levels were associated with worse cognitive function in epsilon 3 epsilon 4 carriers and to a lesser extent in epsilon 3 epsilon 3 carriers, but not in epsilon 2 epsilon 3 carriers. The MMSE score during the entire follow-up period differed between those with high and low serum calcium levels, with 5.5 points in epsilon 3 epsilon 4 carriers (p < 0.001), 1.6 points in epsilon 3 epsilon 3 carriers (p = 0.010), and 0.1 point in epsilon 2 epsilon 3 carriers (p = 0.935). Formal testing showed an interaction between APOE genotype and serum calcium levels in relation to global cognitive function (p = 0.003). Conclusions: In old age, APOE genotype modulates the association between serum calcium levels and cognitive function. High serum calcium levels associate with worse cognitive function, especially in APOE epsilon 4 allele carriers, but not in carriers of the epsilon 2 allele. Neurology (R) 2009; 72: 821-828