Glucose impairment and ghrelin gene variants are associated to cognitive dysfunction.

BACKGROUND AND AIMS: Cognitive state and brain volume have been related to body mass index, abdominal fat, waist-hip ratio, components of metabolic syndrome (MS) and ghrelin. Genetic variations within the ghrelin gene have been recently associated to MS. The aim of our study was to investigate cognitive state by Mini-Mental State Examination (MMSE) in relation to MS components (ATP-III criteria) and ghrelin gene polymorphisms in dwelling individuals aged ≥70. METHODS: 280 subjects (137 men/143 women, age 77.03 ± 5.92) from the Mataró Ageing Study were included. Individuals were phenotypically characterized by anthropometric variables, lipids, glucose, blood pressure and MMSE. SNPs -501AC (rs26802), -994CT (rs26312), -604GA (rs27647), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene were studied. Genotypes were determined by polymerase chain reaction and SNapshot minisequencing. RESULTS: 22.1 % had MMSE <24. MMSE <24 was associated with age (p < 0.001), female gender (p = 0.016), low education (p < 0.001) and glucose impairment or diabetes (p = 0.040). MMSE was influenced by obesity, central obesity, MS and glucose impairment. This latter association remained significant after adjustment by gender, age, alcohol, educational level, GDS and ApoE genotype (p = 0.009). Ghrelin SNPs were associated to MMSE: M72L C/A genotype showed lower score than C/C (p = 0.032, after adjusting for confounders 0.049); L90G A/T genotype showed lower score than A/A (p = 0.054, after adjusting 0.005). MMSE <24 was associated to L90G (39.1 % in A/T genotype vs 19.3 % in A/A, p = 0.026, after adjusting for confounders p = 0.002, OR 6.18 CI 1.93-21.75). CONCLUSIONS: Glucose impairment and L90G Ghrelin gene variant influence cognitive function in old dwelling individuals participating in the Mataró Ageing Study.