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The aging brain and changes in cognitive performance: Findings from morphometry and quantitative susceptibility mapping of iron
Stockholm University, Faculty of Social Sciences, Department of Psychology.ORCID iD: 0000-0001-9411-812X
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.
Keyword [en]
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
Psychology
Identifiers
URN: urn:nbn:se:su:diva-123699ISBN: 978-91-7649-295-6 (print)OAI: oai:DiVA.org:su-123699DiVA: diva2:875958
Public defence
2016-01-15, David Magnussonsalen (U31), Frescati Hagväg 8, Stockholm, 13:00 (English)
Opponent
Supervisors
Available from: 2015-12-21 Created: 2015-12-02 Last updated: 2016-01-18Bibliographically approved
List of papers
1. Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms
Open this publication in new window or tab >>Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms
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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.

Keyword
Aging, MRI, Inflammation, Longitudinal, Parahippocampal gyrus, Cerebellum, Interleukin-1β
National Category
Psychology Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-108565 (URN)10.1016/j.neuroimage.2014.09.042 (DOI)000345393100034 ()
Note

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: 2017-12-05Bibliographically approved
2. Age and sex related differences in subcortical brain iron concentrations among healthy adults
Open this publication in new window or tab >>Age and sex related differences in subcortical brain iron concentrations among healthy adults
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2015 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 122, 385-398 p.Article in journal (Refereed) Published
Abstract [en]

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20–69, ♀ 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5 T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+ 51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person changes in aging.

Keyword
quantitative susceptibility mapping, iron, brain aging, sub-cortical nuclei, gender differences, sex differences
National Category
Psychology Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-121114 (URN)10.1016/j.neuroimage.2015.07.050 (DOI)000363125200037 ()
Available from: 2015-09-24 Created: 2015-09-24 Last updated: 2017-12-01Bibliographically approved
3. Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors
Open this publication in new window or tab >>Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors
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2016 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 126, 15-26 p.Article in journal (Refereed) Published
Abstract [en]

We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.

Keyword
Fluid abilities, Longitudinal, MRI, Memory, Prefrontal cortex, Volume, White matter
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-123702 (URN)10.1016/j.neuroimage.2015.11.028 (DOI)000369289800002 ()26584866 (PubMedID)
Available from: 2015-12-02 Created: 2015-12-02 Last updated: 2017-12-01Bibliographically approved

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