title: The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort.
abstract: OBJECTIVE
  Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years.
  
  
  METHODS
  In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated.
  
  
  RESULTS
  As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found.
  
  
  CONCLUSIONS
  In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia.
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden. Electronic address: anna.zettergren@neuro.gu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Zettergren
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden; Clinical Neurochemistry Lab, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Silke
authors.initials: S
authors.lastname: Kern
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Deborah
authors.initials: D
authors.lastname: Gustafson
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Gudmundsson
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Sigström
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Svante
authors.initials: S
authors.lastname: Östling
authors.affiliation: Department of Pharmacology (EE) Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.affiliation: Clinical Neurochemistry Lab, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Lab, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Skoog
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003430:Cross-Sectional Studies; D003704:Dementia / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D013548:Sweden
chemical_list: C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Late-life depression; angiotensin receptor II type 1; angiotensin-converting enzyme; dementia; gene