title: Macrophage inhibitory cytokine-1/growth differentiation factor 15 as a marker of cognitive ageing and dementia.
abstract: OBJECTIVE
  As a divergent member of the transforming growth factor-β superfamily, macrophage inhibitory cytokine-1 (MIC-1/GDF15) is an autocrine regulatory molecule that plays important roles in diseases, such as cancer and cardiovascular disorders. More recently, this cytokine has been investigated for its contribution to ageing and age-related cognitive decline. This review aims at summarizing existing findings on the relationships of MIC-1/GDF15 with cognition, brain, and dementia in ageing populations and animal models.
  
  
  RESULTS
  In community-dwelling samples, higher circulating MIC-1/GDF15 levels were associated with worsening cognitive function and decline from cognitively normal status to mild cognitive impairment or dementia. Higher MIC-1/GDF15 serum levels were also linked to decreased grey matter volumes and white matter integrity. Brain structural changes were shown to mediate the inverse relationships of MIC-1/GDF15 serum levels with cognition. Animal studies indicated that the expression of MIC-1/GDF15 in response to stress was neuroprotective and even promoted neurogenesis.
  
  
  CONCLUSIONS
  From the available findings, MIC-1/GDF15 can be considered as a marker of age-related cognitive decline and brain structural changes. Combining MIC-1/GDF15 with other biomarkers may provide clinical diagnostic and prognostic utility. Threshold effects should be considered in future studies.
authors.affiliation: aCentre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales bNeuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D000375:Aging / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood; D003071:Cognition; D000066492:Cognitive Aging; D003704:Dementia / Q000097:blood*; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D009369:Neoplasms / Q000097:blood
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15