Association between Mid-Regional Proadrenomedullin Levels and Progression of Deep White Matter Lesions in the Brain Accompanying Cognitive Decline

Article type: Research Article

Authors: Kuriyama, Nagato^{a; b; *} | Ihara, Masafumi^c | Mizuno, Toshiki^b | Ozaki, Etsuko^a | Matsui, Daisuke^a | Watanabe, Isao^a | Koyama, Teruhide^a | Kondo, Masaki^b | Tokuda, Takahiko^b | Tamura, Aiko^b | Yamada, Kei^d | Akazawa, Kentaro^d | Takeda, Kazuo^e | Takada, Akihiro^e | Mizuno, Shigeto^g | Nakagawa, Masanori^f | Watanabe, Yoshiyuki^a

Affiliations: [a] Departments of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan | [b] Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan | [c] Department of Stroke and Cerebrovascular Diseases, Division of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan | [d] Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan | [e] Kyoto Industrial Health Association, Kyoto, Japan | [f] North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan | [g] Department of Endoscopy, Kindai University Nara Hospital, Japan

Correspondence: [*] Correspondence to: Nagato Kuriyama, MD, PhD, Departments of Epidemiology for Community Health and Medicine, and Neurology, Kyoto Prefectural University of Medicine,465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto-city, 602–8566, Japan. Tel.: +81 75 251 5789; Fax: +81 75 251 5799; E-mail: [email protected].

Abstract: Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: Deep white matter lesion, dementia, magnetic resonance imaging, mid-regional proadrenomedullin

DOI: 10.3233/JAD-160901

Journal: Journal of Alzheimer's Disease, vol. 56, no. 4, pp. 1253-1262, 2017