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Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms
Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden; Wayne State University, USA.
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2014 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 103, 334-348 p.Article in journal (Refereed) Published
Abstract [en]

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-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.

Place, publisher, year, edition, pages
2014. Vol. 103, 334-348 p.
Keyword [en]
Aging, MRI, Inflammation, Longitudinal, Parahippocampal gyrus, Cerebellum, Interleukin-1β
National Category
Psychology Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Research subject
URN: urn:nbn:se:su:diva-108565DOI: 10.1016/j.neuroimage.2014.09.042ISI: 000345393100034OAI: diva2:759380

This research was supported by the National Institute on Aging grant R37 AG-11230 to NR. NP was supported by grants FOA11H-090, FOA13H-090, FO2011-0504 and FO2013-0189 from the Swedish Royal Academia of Sciences, Lars Hiertas Memorial Foundation, Solstickan Foundation and Department of Psychology at the Stockholm University (Ann-Charlotte Smedler, Head of the Department). We acknowledge Awantika Deshmukh's contribution to tracing of the ROIs.

Available from: 2014-10-29 Created: 2014-10-29 Last updated: 2015-12-02Bibliographically approved
In thesis
1. The aging brain and changes in cognitive performance: Findings from morphometry and quantitative susceptibility mapping of iron
Open this publication in new window or tab >>The aging brain and changes in cognitive performance: Findings from morphometry and quantitative susceptibility mapping of iron
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brain aging is a heterogeneous phenomenon, and this thesis illustrates how the course of aging can vary within individuals over time and between individuals as a function of age, sex, and genetic variability. We used two contrasts from magnetic resonance imaging (MRI), namely spin-lattice T1-weighted imaging, and quantitative susceptibility mapping (QSM) from gradient-echo images, to picture the aging brain, by means of morphometric measures and brain-iron concentrations. Within each study, the same rigorous imaging acquisitioning protocols were used over large samples sizes of 167-183 individuals, which contribute to the uniqueness of the studies. Most of the current knowledge about the aging brain rests on the foundation of cross-sectional age-related differences, and studies I and III contribute to current knowledge with longitudinal designs to investigate individual rates of change. The importance of genetic variation in relation to regional brain changes was addressed with a specific emphasis on functional polymorphisms involved in pro-inflammatory responses. These studies further shed light on the importance of bi-directional relations between structural integrity and maintained cognitive abilities over time. Study II is the largest study to date to have quantitative susceptibility estimates examined in healthy adults, and the first in-vivo report to show a lowering in overall subcortical brain iron estimates in women from midlife to old age. Studies I and III are unique by examining longitudinal differences in anatomical brain regions using high resolution images from a 4 Tesla scanner. Peripheral vascular risk factors were not strong determinants of either brain- or cognitive changes in the studied samples. The results are discussed in the context of cognitive reserve, the brain maintenance hypothesis, and potential influences of hormones, inflammation and oxidative stress.

Place, publisher, year, edition, pages
Stockholm: Department of Psychology, Stokholm University, 2015. 105 p.
brain aging, volumes, ndividual differences, QSM, cognitive aging, iron, episodic memory, fluid-, crystalized abilities, sex differences, gender differences
National Category
Psychology (excluding Applied Psychology)
Research subject
urn:nbn:se:su:diva-123699 (URN)978-91-7649-295-6 (ISBN)
Public defence
2016-01-15, David Magnussonsalen (U31), Frescati Hagväg 8, Stockholm, 13:00 (English)
Available from: 2015-12-21 Created: 2015-12-02 Last updated: 2016-01-18Bibliographically approved

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