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

• Published in: NeuroImage (Orlando, Fla.) Vol. 103; pp. 334 - 348
• Main Authors: Persson, N., Ghisletta, P., Dahle, C.L., Bender, A.R., Yang, Y., Yuan, P., Daugherty, A.M., Raz, N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2014; Elsevier; Elsevier Limited
• Subjects: Adult; Age; Aged; Aging; Aging - genetics; Aging - pathology; Alleles; Alzheimer's disease; Apolipoprotein E; Apolipoproteins; Biological and medical sciences; Biomarkers; Brain; Brain - pathology; C-reactive protein; Caudate nucleus; Cerebellum; Cortex (frontal); Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene polymorphism; Genetic diversity; Genetic engineering; Genotype; Humans; Hypertension; IL-1β; Image Interpretation, Computer-Assisted; Individuality; Inflammation; Inflammation - complications; Inflammation - genetics; Interleukin-1β; Life span; Longitudinal; Magnetic Resonance Imaging; Male; Medicin och hälsovetenskap; Methylenetetrahydrofolate reductase; Middle Aged; MRI; Organ Size; Parahippocampal gyrus; Polymorphism, Single Nucleotide; Prefrontal cortex; Psychology; psykologi; Putamen; Studies; Substantia alba; Vertebrates: nervous system and sense organs; Visual cortex; Young Adult; Cerebellum; Longitudinal; MRI; Interleukin-1β; Aging; Inflammation; Parahippocampal gyrus; Senescence; Cytokine; Central nervous system; Interleukin 1β; Nuclear magnetic resonance imaging; Encephalon; Polymorphism
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2014.09.042

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. •In healthy adults, 10 brain ROI volumes measured manually twice 2years apart•Average shrinkage was observed in the medial temporal and orbitofrontal cortices.•No mean change noted in lateral prefrontal cortex and prefrontal white matter•Heterogeneity in change was noted in all regions, except the orbitofrontal cortex.•Pro-inflammatory SNPs were linked to parahippocampal and cerebellar shrinkage.