title: Association between Mid-Regional Proadrenomedullin Levels and Progression of Deep White Matter Lesions in the Brain Accompanying Cognitive Decline.
abstract: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain.
  
  
  
  To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline.
  
  
  
  The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels.
  
  
  
  MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008.
  
  
  
  MR-proADM levels were significantly different between the DWML groups and inversely correlated with cognitive function test scores, suggesting that high MR-proADM levels and DWMLs are associated with cognitive decline. Therefore, the MR-proADM level may be an effective candidate as a potential diagnostic surrogate marker of cognitive decline.
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, Division of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ozaki
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsui
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Watanabe
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Kyoto Industrial Health Association, Kyoto, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Kyoto Industrial Health Association, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takada
authors.affiliation: Department of Endoscopy, Kindai University Nara Hospital, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011498:Protein Precursors / Q000097:blood*; D012307:Risk Factors; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin
keywords: Deep white matter lesion; dementia; magnetic resonance imaging; mid-regional proadrenomedullin