title: Regional brain shrinkage over two years: individual differences and effects of pro-inflammatory genetic polymorphisms.
abstract: We examined regional changes in brain volume in healthy adults (N=167, age 19-79years 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-1β (IL-1β 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) ε4 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.
authors.affiliation: Department of Psychology, Stockholm University, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden; Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: N
authors.initials: N
authors.lastname: Persson
authors.affiliation: Faculty of Psychology and Educational Sciences, University of Geneva, Sierre, Switzerland; Switzerland Distance Learning University, Sierre, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Ghisletta
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Dahle
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Bender
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA; Department of Psychology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Daugherty
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA; Department of Psychology, Wayne State University, Detroit, MI 48202, USA. Electronic address: nraz@wayne.edu.
authors.forename: N
authors.initials: N
authors.lastname: Raz
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007206:Individuality; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
keywords: Aging; Cerebellum; Inflammation; Interleukin-1β; Longitudinal; MRI; Parahippocampal gyrus