title: Prediction of Alzheimer's disease using midregional proadrenomedullin and midregional proatrial natriuretic peptide: a retrospective analysis of 134 patients with mild cognitive impairment.
abstract: OBJECTIVE
  Development of biomarkers for early detection of Alzheimer's disease (AD) is a major clinical research goal. On the basis of the hypothesis that cardiovascular risk factors contribute to the pathogenesis of AD, we investigated whether the cardiovascular risk markers midregional proadrenomedullin (MR-proADM) and midregional proatrial natriuretic peptide (MR-proANP) predict a major clinical milestone, ie, conversion from predementia mild cognitive impairment (MCI) to manifest AD.
  
  
  METHODS
  A group of 134 MCI patients, among 137 originally prospectively recruited at the memory disorder clinic at Malmö University Hospital, Malmö, Sweden, between July 1998 and June 2001, was clinically followed for 4-6 years. We determined whether plasma concentrations of MR-proADM and MR-proANP at baseline predicted time to conversion from MCI to clinically diagnosed AD (DSM-III-R). MCI was diagnosed according to Petersen criteria.
  
  
  RESULTS
  During follow-up, 41.8% of MCI patients remained cognitively stable, 42.5% converted to possible and probable AD, and 15.7% converted to other forms of dementia (MCI-other). MCI converters and MCI-other patients showed increased concentrations of MR-proANP and MR-proADM compared to the stable MCI patients (P = .0001). At a cutoff of 87 pmol/L, MR-proANP yielded a sensitivity of 73.7% and a specificity of 64.3% for predicting conversion to AD. The survival analysis showed that higher values of MR-proANP and MR-proADM were associated with progression to AD. In a multivariate Cox regression model including known risk factors, MR-proANP and MR-proADM remained independent risk factors for conversion to AD for patients below the age of 72 years.
  
  
  CONCLUSIONS
  Our study shows that plasma concentrations of MR-proANP and MR-proADM have predictive value in the progression from predementia MCI to clinical AD. Sensitivity was particularly high, which may recommend this test for first-stage screening in patients at risk for AD.
authors.affiliation: Dementia Research Section and Memory Clinic, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany. katharina.buerger@med.uni-muenchen.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Buerger
authors.forename: Olga
authors.initials: O
authors.lastname: Uspenskaya
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartmann
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Moeller
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: Andrea
authors.initials: A
authors.lastname: Ernst
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000097:blood* / Q000175:diagnosis; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; C552580:midregional pro-atrial natriuretic peptide, human; C088633:proadrenomedullin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor