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

From the Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

Address correspondence and reprint requests to Dr. P. van Vliet, Leiden University Medical Center, Department of Gerontology and Geriatrics (C2-R), PO Box 9600, 2300 RC, Leiden, The Netherlands p.van_vliet{at}lumc.nl.

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 34 carriers and to a lesser extent in 33 carriers, but not in 23 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 34 carriers (p < 0.001), 1.6 points in 33 carriers (p = 0.010), and 0.1 point in 23 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 4 allele carriers, but not in carriers of the 2 allele.

Abbreviations: ADL = activities of daily living; CI = confidence interval; FCP = final common pathway; HNE = 4-hydroxynenoral; LDL = low-density lipoprotein; LDT = Letter Digit Coding Test; MMSE = Mini-Mental State Examination; NMDA-R = N-methyl-d-aspartic acid receptor; PLT = Picture Learning Test; PTH = parathyroid hormone; ROS = reactive oxygen species.

Supplemental data at www.neurology.org.

Funded by an Innovative Oriented Research (IOP) grant from the Dutch Ministry of Economic Affairs (grant number IGE01014).

Disclosure: The authors report no disclosures.

Received September 15, 2008. Accepted in final form December 1, 2008.