title: Declines in inflammation predict greater white matter microstructure in older adults.
abstract: Protracted systemic inflammation has been associated with adverse effects on cognition and brain structure and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. We studied 276 black and white older adults (mean age = 83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with c-reactive protein, CRP) was assessed repeatedly over 6 years (i.e., year 2, 4, 6, and 8). Brain magnetic resonance imaging (MRIs) were obtained at years 10-11 with diffusion tensor imaging; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal (superior longitudinal fasciculus [SLF]-dorsal) and temporal (SLF-temporal; uncinate) white matter tracts. Mean CRP values significantly declined (t = -5.54, p < 0.0001) over 6 years, and subject-specific slopes (best linear unbiased predictors of slopes) all showed a decline (mean = -0.57, standard deviation = 0.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal (beta = -0.0052, standard error [SE] = 0.003; 95% confidence interval [CI] = -0.0103 to -0.0025, p = 0.04), SLF-temporal (beta = -0.0109, SE = 0.004; 95% CI = -0.0189 to -0.0029, p = 0.008), and uncinate (beta = -0.0067, SE = 0.003; 95% CI = -0.0132 to -0.0001, p = 0.05) fasciculi. Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors.
authors.affiliation: Neurology Department, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: bbettcher@memory.ucsf.edu.
authors.forename: Brianne Magouirk
authors.initials: BM
authors.lastname: Bettcher
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; San Francisco VA Medical Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Boudreau
authors.affiliation: Neurology Department, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Aizenstein
authors.affiliation: The Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
authors.affiliation: The Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.affiliation: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: The Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Satterfield
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D066127:White Matter / Q000473:pathology* / Q000648:ultrastructure*
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: CRP; Diffusion tensor imaging; Longitudinal; Pro-inflammatory