Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Research Article Dement Geriatr Cogn Disord 2010;30:569–578 DOI: 10.1159/000322092 Systemic Inflammation Is Associated with MCI and Its Subtypes: The Sydney Memory and Aging Study Julian N. Trollor   a, b Evelyn Smith   a Bernhard T. Baune   g Nicole A. Kochan   b, d Lesley Campbell   e, f Katherine Samaras   e, f John Crawford   b Henry Brodaty   b, c Perminder Sachdev   b, d   a  Department of Developmental Disability Neuropsychiatry, b  Brain and Aging Research Program, School of Psychiatry, and c  Dementia Collaborative Research Centre, School of Psychiatry, University of New South Wales, Sydney, N.S.W., d  Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, N.S.W., e  Garvan Institute of Medical Research, and f  Department of Endocrinology, St Vincent’s Hospital, Darlinghurst, N.S.W., and g  Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Qld., Australia differences were apparent. Nonamnestic multiple domain MCI was associated with higher levels of IL-1  and IL-12, TNF-  and SAA compared to cognitively normal, amnestic MCI (single and multiple domain) and nonamnestic single do- main MCI. PAI-1 levels were higher in cognitively normal and nonamnestic multiple domain MCI than in amnestic multiple domain MCI. Conclusion: Our findings suggest an associa- tion between specific inflammatory markers and MCI sub- types, highlight sex differences in the association with MCI, and point to a discrete impact of systemic inflammation on cognition. Copyright © 2011 S. Karger AG, Basel Introduction The proposed revision of the Diagnostic and Statisti- cal Manual of Mental Disorders (DSM-V; dsm5.org) has included a new diagnostic syndrome of the minor neuro- cognitive disorder, which recognizes the clinical needs of Key Words Inflammation  Cytokines  Inflammatory markers  Mild cognitive impairment  Dementia Abstract Background/Aims: Raised low-grade systemic inflamma- tion has been associated with dementia, and preliminary studies suggest an association with mild cognitive impair- ment (MCI). This study examines the relationship between systemic inflammation and MCI subtypes. Methods: We measured the inflammatory markers C-reactive protein, in- terleukins (IL)-1 , -6, -8, -10 and -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A (SAA), tumor necrosis factor-  (TNF- ) and vascular adhesion molecule-1 (VCAM- 1) in the Sydney Memory and Ageing Study (MAS) cohort, a longitudinal study of 1,037 Australians aged 70–90 years. Re- sults: After adjusting for possible confounding variables, levels of TNF-  and SAA were higher in participants with MCI compared to cognitively normal individuals, and some sex Accepted: October 14, 2010 Published online: January 20, 2011 Assoc. Prof. Julian Trollor Department of Developmental Disability Neuropsychiatry University of New South Wales 34 Botany Road, Sydney, NSW 2052 (Australia) Tel. +61 2 9931 9160, Fax +61 2 9931 9154, E-Mail j.trollor  @  unsw.edu.au © 2011 S. Karger AG, Basel 1420–8008/10/0306–0569$26.00/0 Accessible online at: www.karger.com/dem