title: Genetically increased risk of sleep disruption in Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD).
  
  
  METHODS
  A case-control association analysis.
  
  
  METHODS
  Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A).
  
  
  METHODS
  Patients with AD diagnosed according to standard criteria.
  
  
  METHODS
  Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods.
  
  
  RESULTS
  Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype.
  
  
  CONCLUSIONS
  We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.
authors.affiliation: Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland, United Kingdom. david.craig@qub.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hart
authors.forename: A Peter
authors.initials: AP
authors.lastname: Passmore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D016022:Case-Control Studies; D017281:Cost of Illness; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood; D008995:Monoamine Oxidase / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D012701:Serotonin / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E; D012701:Serotonin; D008995:Monoamine Oxidase; D008550:Melatonin