4.7 Article

Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms

Journal

NEUROIMAGE
Volume 103, Issue -, Pages 334-348

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2014.09.042

Keywords

Aging; MRI; Inflammation; Longitudinal; Parahippocampal gyrus; Cerebellum; Interleukin-1 beta

Funding

  1. National Institute on Aging [R37 AG-11230]
  2. Swedish Royal Academia of Sciences [FOA11H-090, FOA13H-090, FO2011-0504, FO2013-0189]
  3. Lars Hiertas Memorial Foundation
  4. Solstickan Foundation
  5. Department of Psychology at the Stockholm University

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We examined regional changes in brain volume in healthy adults (N=167, age 19-79 years at baseline; N=90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1 beta (IL-1 beta C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) epsilon 4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. (C) 2014 Elsevier Inc. All rights reserved.

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