title: Glucose impairment and ghrelin gene variants are associated to cognitive dysfunction.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clínic I Universitari of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: M L
authors.initials: ML
authors.lastname: Mansego
authors.forename: M
authors.initials: M
authors.lastname: Serra-Prat
authors.forename: E
authors.initials: E
authors.lastname: Palomera
authors.forename: X
authors.initials: X
authors.lastname: Boquet
authors.forename: J F
authors.initials: JF
authors.lastname: Chaves
authors.forename: M
authors.initials: M
authors.lastname: Puig-Domingo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism*; D003072:Cognition Disorders / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D054439:Ghrelin / Q000235:genetics*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D013030:Spain
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D054439:Ghrelin