title: Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.
abstract: Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case-control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community. All subjects underwent detailed neuropsychological assessment, 3-Tesla magnetic resonance imaging, and venous blood draw. Subjects were classified as CIND or AD based on clinical criteria, while significant CeVD was defined as the presence of cortical infarcts and/or 2 lacunes or more, and/or confluent white matter hyperintensities (WMHs) in 2 or more brain regions. A total of 324 subjects were included in the study, of whom 80 had no cognitive impairment, 144 CIND and 100with AD. Higher GDF-15 levels were significantly associated with disease groups, especially in the presence of CeVD, namely, CIND with CeVD (odds ratios [OR]: 7.21; 95% confidence interval [CI]: 2.14-24.27) and AD with CeVD (OR: 21.87; 95% CI: 2.01-237.43). Among the different CeVD markers, only WMH was associated with higher GDF-15 levels (OR: 3.97; 95% CI: 1.79-8.83). The associations between GDF-15 and cognitive impairment as well as with WMH remained significant after excluding subjects with cardiovascular diseases. In conclusion, we showed that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore Memory Aging and Cognition Centre, National University Health System Cardiovascular Research Institute, National University Heart Centre, Singapore Departments of Neurology and Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands Raffles Neuroscience Centre, Raffles Hospital, Singapore.
authors.forename: Yuek Ling
authors.initials: YL
authors.lastname: Chai
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.forename: Jenny P C
authors.initials: JPC
authors.lastname: Chong
authors.forename: Yan Xia
authors.initials: YX
authors.lastname: Ng
authors.forename: Oi Wah
authors.initials: OW
authors.lastname: Liew
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Mitchell K P
authors.initials: MKP
authors.lastname: Lai
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15