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O2–06–04: Amyloid β42–level lowering non–steroidal anti–inflammatory drugs and the risk of Alzheimer's disease
Author(s) -
Haag Mendel D.,
Oijen Marieke,
Jan de Jong Frank,
Hofman Albert,
Stijnen Theo,
Stricker Bruno H.,
Breteler Monique M.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.150
Subject(s) - medicine , dementia , hazard ratio , discontinuation , disease , population , proportional hazards model , concomitant , rotterdam study , lower risk , confidence interval , environmental health
of brain and WMH volumes were obtained from 1974 Framingham Heart Study Offspring Cohort participants free from clinical stroke, TIA or dementia with an age range of 35-85 years (60 9; 53% women). To adjust for head size, both measures were divided by total cranial volume (TCV); WMH was log transformed to normalize variance. MRI measures were associated with 8 inflammatory biomarkers including CD40 ligand (CD40L), C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), osteoprotegerin (OPG), and P-selectin after log transformation, adjusting for age, sex, systolic blood pressure (BP), diastolic BP, body mass index, height, total high density lipoprotein, smoking status, fasting glucose, triglycerides, diabetes, BP treatment, hormone replacement therapy, lipid lowering treatment, aspirin, atrial fibrillation, prevalent CVD, and ECG left ventricular hypertrophy. Results: In multivariable models, the inflammatory markers were associated with TBV (p .0001) but not WMH. Backward elimination (terms with p 0.05 retained) revealed two significant inverse associations with TBV including IL-6 ( –0.29, p .002) and OPG ( –0.77, p .001). The estimated mean change in TBV per interquartile range of IL-6 –0.26 (p .002) and OPG –0.30 (p .001). Findings were similar when the analyses were re-run excluding individuals with prevalent CVD. Conclusions: Our analyses revealed that IL-6 and OPG, both markers of systemic inflammation, were inversely associated with TBV; however, no inflammatory marker was associated with WMH. Though our analyses are cross-sectional and unable to establish causality, we propose that elevated inflammatory markers may be implicated in accelerating age-related atrophy. The etiology of this association remains unclear and requires further investigation.