title: Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study.
abstract: BACKGROUND
  Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia.
  
  
  OBJECTIVE
  We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals.
  
  
  METHODS
  178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited.
  
  
  METHODS
  Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE).
  
  
  RESULTS
  The DD genotype for ACE was independently associated ( b  = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07).
  
  
  CONCLUSIONS
  Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia.
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Georgiopoulos
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Chrysohoou
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, Sassari I-07100, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Errigo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, Sassari I-07100, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pes
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Metaxa
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Zaromytidou
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Skoumas
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Kariori
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Lazaros
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Vogiatzi
authors.affiliation: Estonian Institute for Population Studies, Tallinn University, Uus-Sadama 5, Room M-553, 10120 Tallinn, Estonia.|IACCHOS Université Catholique de Louvain, Charleroi, 1, Place de l'Université B-1348 Louvain-la-Neuve, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Poulain
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Tousoulis
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Pitsavos
authors.affiliation: First Department of Cardiology, Hippokration Hospital, University of Athens, Vas. Sofias 114, 11527, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology; D003071:Cognition / Q000502:physiology; D004452:Echocardiography / Q000379:methods; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008019:Life Style; D008297:Male; D000073216:Mental Status and Dementia Tests; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A