Anders M. Fjell

Effects of age on volumes of cortex, white matter and subcortical structures

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.

Brain Maturation in Adolescence and Young Adulthood: Regional Age-Related Changes in Cortical Thickness and White Matter Volume and Microstructure

The development of cortical gray matter, white matter (WM) volume, and WM microstructure in adolescence is beginning to be fairly well characterized by structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) studies. However, these aspects of brain development have rarely been investigated concurrently in the same sample and hence the relations between them are not understood. We delineated the age-related changes in cortical thickness, regional WM volume, and diffusion characteristics and investigated the relationships between these properties of brain development. One hundred and sixty-eight healthy participants aged 8-30 years underwent sMRI and DTI. The results showed regional age-related cortical thinning, WM volume increases, and changes in diffusion parameters. Cortical thickness was the most strongly age-related parameter. All classes of measures showed unique associations with age. The results indicate that cortical thinning in adolescence cannot be explained by WM maturation in underlying regions as measured by volumetry or DTI. Moderate associations between cortical thickness and both volume and diffusion parameters in underlying WM regions were also found, although the relationships were not strong. It is concluded that none of the measures are redundant and that the integration of the 3 will yield a more complete understanding of brain maturation.

Life-Span Changes of the Human Brain White Matter: Diffusion Tensor Imaging (DTI) and Volumetry

Magnetic resonance imaging volumetry studies report inverted U-patterns with increasing white-matter (WM) volume into middle age suggesting protracted WM maturation compared with the cortical gray matter. Diffusion tensor imaging (DTI) is sensitive to degree and direction of water permeability in biological tissues, providing in vivo indices of WM microstructure. The aim of this cross-sectional study was to delineate age trajectories of WM volume and DTI indices in 430 healthy subjects ranging 8-85 years of age. We used automated regional brain volume segmentation and tract-based statistics of fractional anisotropy, mean, and radial diffusivity as markers of WM integrity. Nonparametric regressions were used to fit the age trajectories and to estimate the timing of maximum development and deterioration in aging. Although the volumetric data supported protracted growth into the sixth decade, DTI indices plateaued early in the fourth decade across all tested regions and then declined slowly into late adulthood followed by an accelerating decrease in senescence. Tractwise and voxel-based analyses yielded regional differences in development and aging but did not provide ample evidence in support of a simple last-in-first-out hypothesis of life-span changes.

High Consistency of Regional Cortical Thinning in Aging across Multiple Samples

Cross-sectional magnetic resonance imaging (MRI) studies of cortical thickness and volume have shown age effects on large areas, but there are substantial discrepancies across studies regarding the localization and magnitude of effects. These discrepancies hinder understanding of effects of aging on brain morphometry, and limit the potential usefulness of MR in research on healthy and pathological age-related brain changes. The present study was undertaken to overcome this problem by assessing the consistency of age effects on cortical thickness across 6 different samples with a total of 883 participants. A surface-based segmentation procedure (FreeSurfer) was used to calculate cortical thickness continuously across the brain surface. The results showed consistent age effects across samples in the superior, middle, and inferior frontal gyri, superior and middle temporal gyri, precuneus, inferior and superior parietal cortices, fusiform and lingual gyri, and the temporo-parietal junction. The strongest effects were seen in the superior and inferior frontal gyri, as well as superior parts of the temporal lobe. The inferior temporal lobe and anterior cingulate cortices were relatively less affected by age. The results are discussed in relation to leading theories of cognitive aging.

Structural Brain Changes in Aging: Courses, Causes and Cognitive Consequences

The structure of the brain is constantly changing from birth throughout the lifetime, meaning that normal aging, free from dementia, is associated with structural brain changes. This paper reviews recent evidence from magnetic resonance imaging (MRI) studies about age-related changes in the brain. The main conclusions are that (1) the brain shrinks in volume and the ventricular system expands in healthy aging. However, the pattern of changes is highly heterogeneous, with the largest changes seen in the frontal and temporal cortex, and in the putamen, thalamus, and accumbens. With modern approaches to analysis of MRI data, changes in cortical thickness and subcortical volume can be tracked over periods as short as one year, with annual reductions of between 0.5% and 1.0% in most brain areas. (2) The volumetric brain reductions in healthy aging are likely only to a minor extent related to neuronal loss. Rather, shrinkage of neurons, reductions of synaptic spines, and lower numbers of synapses probably account for the reductions in grey matter. In addition, the length of myelinated axons is greatly reduced, up to almost 50%. (3) Reductions in specific cognitive abilities--for instance processing speed, executive functions, and episodic memory--are seen in healthy aging. Such reductions are to a substantial degree mediated by neuroanatomical changes, meaning that between 25% and 100% of the differences between young and old participants in selected cognitive functions can be explained by group differences in structural brain characteristics.

Heterogeneity in Subcortical Brain Development: A Structural Magnetic Resonance Imaging Study of Brain Maturation from 8 to 30 Years

Brain development during late childhood and adolescence is characterized by decreases in gray matter (GM) and increases in white matter (WM) and ventricular volume. The dynamic nature of development across different structures is, however, not well understood, and the present magnetic resonance imaging study took advantage of a whole-brain segmentation approach to describe the developmental trajectories of 16 neuroanatomical volumes in the same sample of children, adolescents, and young adults (n = 171; range, 8–30 years). The cerebral cortex, cerebral WM, caudate, putamen, pallidum, accumbens area, hippocampus, amygdala, thalamus, brainstem, cerebellar GM, cerebellar WM, lateral ventricles, inferior lateral ventricles, third ventricle, and fourth ventricle were studied. The cerebral cortex was further analyzed in terms of lobar thickness and surface area. The results revealed substantial heterogeneity in developmental trajectories. GM decreased nonlinearly in the cerebral cortex and linearly in the caudate, putamen, pallidum, accumbens, and cerebellar GM, whereas the amygdala and hippocampus showed slight, nonlinear increases in GM volume. WM increased nonlinearly in both the cerebrum and cerebellum, with an earlier maturation in cerebellar WM. In addition to similarities in developmental trajectories within subcortical regions, our results also point to differences between structures within the same regions: among the basal ganglia, the caudate showed a weaker relationship with age than the putamen and pallidum, and in the cerebellum, differences were found between GM and WM development. These results emphasize the importance of studying a wide range of structural variables in the same sample, for a broader understanding of brain developmental principles.

One year brain atrophy evident in healthy aging

An accurate description of changes in the brain in healthy aging is needed to understand the basis of age-related changes in cognitive function. Cross-sectional magnetic resonance imaging (MRI) studies suggest thinning of the cerebral cortex, volumetric reductions of most subcortical structures, and ventricular expansion. However, there is a paucity of detailed longitudinal studies to support the cross-sectional findings. In the present study, 142 healthy elderly participants (60–91 years of age) were followed with repeated MRI, and were compared with 122 patients with mild to moderate Alzheimers disease (AD). Volume changes were measured across the entire cortex and in 48 regions of interest. Cortical reductions in the healthy elderly were extensive after only 1 year, especially evident in temporal and prefrontal cortices, where annual decline was ∼0.5%. All subcortical and ventricular regions except caudate nucleus and the fourth ventricle changed significantly over 1 year. Some of the atrophy occurred in areas vulnerable to AD, while other changes were observed in areas less characteristic of the disease in early stages. This suggests that the changes are not primarily driven by degenerative processes associated with AD, although it is likely that preclinical changes associated with AD are superposed on changes due to normal aging in some subjects, especially in the temporal lobes. Finally, atrophy was found to accelerate with increasing age, and this was especially prominent in areas vulnerable to AD. Thus, it is possible that the accelerating atrophy with increasing age is due to preclinical AD.

Consistent neuroanatomical age-related volume differences across multiple samples.

Magnetic resonance imaging (MRI) is the principal method for studying structural age-related brain changes in vivo. However, previous research has yielded inconsistent results, precluding understanding of structural changes of the aging brain. This inconsistency is due to methodological differences and/or different aging patterns across samples. To overcome these problems, we tested age effects on 17 different neuroanatomical structures and total brain volume across five samples, of which one was split to further investigate consistency (883 participants). Widespread age-related volume differences were seen consistently across samples. In four of the five samples, all structures, except the brainstem, showed age-related volume differences. The strongest and most consistent effects were found for cerebral cortex, pallidum, putamen and accumbens volume. Total brain volume, cerebral white matter, caudate, hippocampus and the ventricles consistently showed non-linear age functions. Healthy aging appears associated with more widespread and consistent age-related neuroanatomical volume differences than previously believed.

Effects of memory training on cortical thickness in the elderly

The brains ability to alter its functional and structural architecture in response to experience and learning has been extensively studied. Mental stimulation might serve as a reserve mechanism in brain aging, but macrostructural brain changes in response to cognitive training have been demonstrated in young participants only. We examined the short-term effects of an intensive memory training program on cognition and brain structure in middle-aged and elderly healthy volunteers. The memory trainers completed an 8-week training regimen aimed at improving verbal source memory utilizing the Method of Loci (MoL), while control participants did not receive any intervention. Both the memory trainers and the controls underwent magnetic resonance imaging (MRI) scans and memory testing pre and post 8 weeks of training or no training, respectively. Cortical thickness was automatically measured across the cortical mantle, and data processing and statistical analyses were optimized for reliable detection of longitudinal changes. The results showed that memory training improved source memory performance. Memory trainers also showed regional increases in cortical thickness compared with controls. Furthermore, thickness change in the right fusiform and lateral orbitofrontal cortex correlated positively with improvement in source memory performance, suggesting a possible functional significance of the structural changes. These findings demonstrate that systematic mental exercise may induce short-term structural changes in the aging human brain, indicating structural brain plasticity in elderly. The present study included short-term assessments, and follow-up studies are needed in order to assess whether such training indeed alters the long-term structural trajectories.

Combining MR Imaging, Positron-Emission Tomography, and CSF Biomarkers in the Diagnosis and Prognosis of Alzheimer Disease

BACKGROUND AND PURPOSE: Different biomarkers for AD may potentially be complementary in diagnosis and prognosis of AD. Our aim was to combine MR imaging, FDG-PET, and CSF biomarkers in the diagnostic classification and 2-year prognosis of MCI and AD, by examining the following: 1) which measures are most sensitive to diagnostic status, 2) to what extent the methods provide unique information in diagnostic classification, and 3) which measures are most predictive of clinical decline. MATERIALS AND METHODS: ADNI baseline MR imaging, FDG-PET, and CSF data from 42 controls, 73 patients with MCI, and 38 patients with AD; and 2-year clinical follow-up data for 36 controls, 51 patients with MCI, and 25 patients with AD were analyzed. The hippocampus and entorhinal, parahippocampal, retrosplenial, precuneus, inferior parietal, supramarginal, middle temporal, lateral, and medial orbitofrontal cortices were used as regions of interest. CSF variables included Aβ42, t-tau, p-tau, and ratios of t-tau/Aβ42 and p-tau/Aβ42. Regression analyses were performed to determine the sensitivity of measures to diagnostic status as well as 2-year change in CDR-SB, MMSE, and delayed logical memory in MCI. RESULTS: Hippocampal volume, retrosplenial thickness, and t-tau/Aβ42 uniquely predicted diagnostic group. Change in CDR-SB was best predicted by retrosplenial thickness; MMSE, by retrosplenial metabolism and thickness; and delayed logical memory, by hippocampal volume. CONCLUSIONS: All biomarkers were sensitive to the diagnostic group. Combining MR imaging morphometry and CSF biomarkers improved diagnostic classification (controls versus AD). MR imaging morphometry and PET were largely overlapping in value for discrimination. Baseline MR imaging and PET measures were more predictive of clinical change in MCI than were CSF measures.