title: Hyperhomocysteinemia, intima-media thickness and C677T MTHFR gene polymorphism: a correlation study in patients with cognitive impairment.
abstract: OBJECTIVE
  Intima-media thickness (IMT) seems associated with risk of Alzheimer disease (AD). Homocysteine (hcy) is a risk factor for vascular diseases and dementia. This study aimed at investigating the possible relationship among IMT, plasma hcy and C677T methylentetrahydrofolate reductase (MTHFR) polymorphism in relation to cognitive status.
  
  
  METHODS
  Sixty-three patients with cognitive impairment and 64 controls underwent biochemical, neuropsychological and carotid ultrasound assessment.
  
  
  RESULTS
  After age and folate adjustment, plasma hcy correlated with both Mini Mental State Examination (MMSE) score (r=-0.7, p<0.01) and IMT (r=0.7, p<0.01). Among patients with cognitive impairment, carriers of TT677 MTHFR genotype had plasma hcy (p<0.001) and IMT (p<0.01) values higher than non carriers. Furthermore, multiple regression analysis showed that MMSE scores were associated with plasma hcy (beta=-0.3, p=0.01), IMT (beta=-0.3, p=0.01) and TT677 MTHFR genotype (beta=-0.3, p=0.02). Structural equation modelling showed that the relation between hcy levels and MMSE score was partly direct (parameter estimate=-0.6; p=0.01) and partly mediated by IMT values (parameter estimate=-0.4; p=0.03). Finally, IMT resulted associated with hypertension (parameter estimate=0.8; p<0.0001).
  
  
  CONCLUSIONS
  Our findings suggest that TT677 MTHFR genotype promotes plasma homocysteine increase which in turn may favour intima-media thickening in patients with cognitive impairment. Hcy may promote neuronal damage through multiple mechanisms, including a micro-vascular damage, mediated by IMT increase, and a direct neuro-toxic effect.
authors.affiliation: Neurologia Clinica, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, Rome, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Gorgone
authors.forename: Francesca
authors.initials: F
authors.lastname: Ursini
authors.forename: Claudia
authors.initials: C
authors.lastname: Altamura
authors.forename: Federica
authors.initials: F
authors.lastname: Bressi
authors.forename: Mario
authors.initials: M
authors.lastname: Tombini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curcio
authors.forename: Paola
authors.initials: P
authors.lastname: Chiovenda
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Mauro
authors.initials: M
authors.lastname: Silvestrini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
authors.forename: Francesco
authors.initials: F
authors.lastname: Pisani
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri