Age-related Microstructural Changes Research Articles

The Age-related Microstructural Changes of the Cortical Gray and White Matter Ratios on T2-, FLAIR and T1-weighted MR Images

Purpose : The purpose of this study was to investigate the microstructural changes according to aging on the thickness and signal intensity (SI) of the cortical gray matter (GM) and white matter (WM) on the T2-, fluid-attenuated inversion recovery (FLAIR) and T1- weighted MR images in normal subjects. Materials and Methods : The 10, 20, 30, 40, 50, 60, 70, 80 and 90 year age groups of men and women (each 10 individuals) who underwent routine brain MRI, including the T2-, FLAIR and T1- weighted images, were selected for this study. We measured the thickness and the SI of the cortical GM and WM at the postcentral gyrus, which has an even thickness at the level of centrum semiovale, on the axial scans and we calculated the mean values of the thickness ratio of the gray/white matter (TRGW) and the signal intensity ratio of the gray/white matter (SRGW), and we compared the ratios of each age group. Results : On the T2-weighted images, the TRGWs were 0.81 and 0.79 at the age of 10 and they were 0.73 and 0.71 at the age of 90 in the men and women, respectively. So, the GM thickness was decreased more than the WM thickness was with aging. On the FLAIR images, the TRGWs were 1.09 and 1.00 at the age of 10 and they were 1.11 and 0.95 at the age of 70 in the men and women, respectively. On the T1weighted images, the TRGWs were 0.66 and 0.80 at the age of 10, and the ratio was changed to 0.90 and 0.78 at the age of 90 in the men and women, respectively. On the T2-weighted image, the SRGWs were 1.53 and 1.43 at the age of 10, and they were 1.23 and 1.27 at the age of 90 in the men and women, respectively. On the FLAIR images, the SRGWs were 1.23 and 1.25 at the age of 10 and they were 1.06 and 1.05 at the age of 90 in the men and women, respectively. On the T1-weighted images, the SRGWs were 0.86 and 0.85 at the age of 10, and they were 0.90 and 0.87 at the age of 90 in the men and women, respectively. Conclusion : We suggest that the age-related microstructural changes of the thickness and the SI of the cortical GM and WM on the T2-, FLAIR and T1- weighted images are unique, and so this knowledge will be helpful to differentiate neurodegenerative disease from normal aging of the brain.

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy offspring having a parent with BD were compared with those in healthy controls. A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity were examined using whole-brain analyses, co-varying for age. Group-by-age interactions showed a linear increase in FA and a linear decrease in RD in CONT in the left corpus callosum and right inferior longitudinal fasciculus. In HBO, there was a linear decrease in FA and an increase in RD with age in the left corpus callosum and no relation between FA or RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed linear and showed nonlinear relations between FA and RD and age in these regions in CONT and HBO. This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO compared with CONT in the corpus callosum and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO.

Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys

Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatta). Further, we determined if long-term 30% calorie restriction (CR) reduced IL-6 and attenuated its association with lower tissue volume and density. Voxel-based morphometry (VBM) and diffusion-weighted voxelwise analyses were conducted. IL-6 was associated with less global gray and white matter (GM and WM), as well as smaller parietal and temporal GM volumes. Lower fractional anisotropy (FA) was associated with higher IL-6 levels along the corpus callosum and various cortical and subcortical tracts. Higher IL-6 concentrations across subjects were also associated with increased mean diffusivity (MD) throughout many brain regions, particularly in corpus callosum, cingulum, and parietal, frontal, and prefrontal areas. CR monkeys had significantly lower IL-6 and less associated atrophy. An IL-6×CR interaction across modalities also indicated that CR mitigated IL-6 related changes in several brain regions compared to controls. Peripheral IL-6 levels were correlated with atrophy in regions sensitive to aging, and this relationship was decreased by CR.

Age-related microstructural changes in subcortical white matter during postadolescent periods in men revealed by diffusion-weighted MR imaging

Continuous maturation of cerebral white matter (WM) in the postadolescent period is not fully understood. To elucidate the time course and location of possible postadolescent maturational changes in cerebral WM, we studied 60 healthy male subjects who were in their second to seventh decade using diffusion-weighted imaging. Mean diffusivity (MD) in subcortical WM was measured in 78 cortical regions in each subject's brain using an automated method. Regression analysis was used to model the age-related change in MD by either a linear or a quadratic function in each region. Age-related changes in subcortical MD were best modeled by either a linear function or a quadratic function in 27 regions including language-related regions, visual or multimodal areas in the bilateral occipital and temporal lobes, limbic areas including the bilateral parahippocampal gyri, and the bilateral postcentral and left precentral gyri. In these regions, the MD rapidly decreased until middle age and thereafter reached a plateau. Our results revealed microstructural changes in local subcortical WM and suggests a continuing maturational process in postoadolescent periods.

Microstructural alterations of the retinal arterial blood column along the vessel axis in healthy volunteers with age

Abstract Purpose We demonstrated previously that roughness of the retinal arterial blood column measured along the vessel axis increases in anamnestically healthy volunteers with increasing age. We termed it longitudinal retinal arterial profile (LAP). Whether LAP is altered with age in medically supervised healthy persons is investigated. Methods 82 medically healthy volunteers were examined by Dynamic Vessel Analyzer (IMEDOS, Jena, Germany) using stimulation with flickering light. 3 age groups were formed: young (N=27, 30,5±4,3 years), middle age (N=28, 42,3±3,3 years) and seniors (N=27, 64,0±5,0 years). Included in the analysis were volunteers without medical vascular risk factors defined as: blood pressure < 140/90 mmHg, HDL > 35 mg/dl, LDL < 190 mg/dl and glucose levels < 110 mg/dl. Retinal arterial diameters were measured along 1 mm vessel segments to obtain LAP. Differences were analyzed using Fourier transformation. Results In all age groups LAP do not change during all stages of the arterial response. Arterial diameters in the senior group were reduced in comparison to the young group at all stages of the vessel reaction (p<0,05). There are differences in LAP between the age groups. Compared to young persons, seniors showed significantly diminished waves with a period of 417 µm at all stages of the arterial reaction, whereas young volunteers showed less pronounced waves with a period of 208 µm (p<0,05). Conclusion Our results represent the healthy aging process in retinal vasculature. Age related microstructural changes in longitudinal profiles of retinal arteries in medically healthy persons might be an indication for alterations in the vascular endothelium and smooth musculature.

Does internal longitudinal microstructure of retinal veins change with age in medically healthy persons?

Abstract Purpose We demonstrated previously that roughness of the retinal arterial blood column measured along the vessel axis, termed longitudinal arterial profile (LAP) increases significantly in anamnesticly healthy volunteers with increasing age. Recently we have demonstrated age related changes in LAP of medically healthy persons. Whether longitudinal retinal venous profiles (LVP) are altered with age in this group is investigated. Methods 83 medically healthy volunteers were examined by Dynamic Vessel Analyzer (IMEDOS, Jena, Germany) using stimulation with flickering light. 3 age groups were formed: young (N=28, 30,2±4,3 years), middle age (N=28, 42,3±3,3 years) and seniors (N=27, 64,0±5,0 years). Included in the analysis were volunteers without medical vascular risk factors defined as: blood pressure < 140/90 mmHg, HDL > 35 mg/dl, LDL < 190 mg/dl and glucose levels < 110 mg/dl. Retinal venous diameters were measured along 1 mm vessel segments to obtain LVP. Differences were analyzed using Fourier transformation. Results In all age groups power spectra of LVP do not change during all stages of the venous response to the stimulation. There were no significant differences in LVP between the age groups. Venous diameters in middle‐age group were reduced in comparison to the young group at all stages of vessel reaction (p<0,05). Conclusion Our results indicate that in contrast to retinal arteries retinal veins of validated healthy volunteers do not undergo age related microstructural changes. Hence previously reported age related decrease of retinal venous diameter might have physiologic origin due to reduced blood flow in retinal microcirculation with age, not because of structural changes of venous wall.

Age-and region-dependent changes in three-dimensional microstructural properties of proximal femoral trabeculae

This study investigated regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. The results demonstrate that age-related changes in trabecular microstructure significantly varied from different sub-regions of the proximal femur. We hypothesize that the age-related changes in trabecular bone microstructure appear to be varied from specific anatomic sub-regions of the proximal femur followed by non-uniform bone loss. The purpose of this study was therefore to explore regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. A total of 162 trabecular bone cores from six regions of 27 femora of male cadaver donors were scanned using micro-computed tomography (micro-CT). The following microstructural parameters were calculated: bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), structure model index (SMI), and degree of anisotropy (DOA). Age-related changes in trabecular microstructure varied from different regions of the proximal femur. There was a significant decrease in bone volume fraction and an almost identical decrease in trabecular thickness associated with aging at any region. Regional analysis demonstrated a significant difference in BV/TV, Tb.Th, Tb.Sp, Tb.N and DOA between superior and inferior neck, as well as a significant difference in BV/TV, Tb.Sp, Tb.N, SMI and DOA between superior and inferior trochanter. Age-related changes in bone loss and trabecular microstructure within the male proximal femur are not uniform in this cadaveric population.

Evidence of Subcortical and Cortical Aging of the Acoustic Pathway: A Diffusion Tensor Imaging (DTI) Study

During aging, there is evidence of microstructural changes in certain cortical and subcortical brain regions. Diffusion tensor imaging (DTI) is used to study age related microstructural changes in the acoustic pathway. Twenty healthy volunteers (mean age 28.5 years) and 15 healthy volunteers (mean age 61.3 years) were examined using a 1.5-T MR system with a high-resolution T1-weighted sequence and an integrated parallel imaging technique DTI Echo-planar-imaging (EPI) sequence. For reliability, 10 subjects underwent a second examination 2 days later. The fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in six brain regions of the auditory pathway. We found no left/right asymmetry in the selected brain structures. There were no significant differences (P < .05) in the ADC and FA in the lateral lemniscus and medial geniculate body of young and elderly subjects. However, FA was significantly increased (P < .05) in the inferior colliculus and decreased in the auditory radiation, the superficial temporal gyrus, and the transverse temporal gyrus in the elder subjects than in the younger ones. There were no significant differences in anisotropy in subsequent examinations in the younger individuals. These findings suggest evidence of age-related changes in the acoustic pathway. These changes are associated with a decrease in anisotropy mainly in the cortical grey and white matter rather than in the subcortical regions. Our DTI measurements were reproducible.

Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging

Age-related microstructural changes in brain white matter can be studied by utilizing indices derived from diffusion tensor imaging (DTI): apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The objective of this study is to examine alterations in FA and ADC by employing exploratory voxel-based analysis (VBA) and region(s) of interest (ROI)-based analysis. A highly nonlinear registration algorithm was used to align the ADC and FA image volumes of different subjects to perform accurate voxel-level statistics for two age groups, as well as for hemispheric asymmetry for both age groups. VBA shows significant age-related decline in FA with frontal predominance (frontal white matter, and genu and anterior body of the corpus callosum), superior portions of a splenium and highly oriented fibers of the posterior limb of the internal capsule and the anterior and posterior limbs of the external capsule. Hemispheric asymmetry of FA, as assessed by VBA, showed that for the young-age group, significant right-greater-than-left asymmetry exists in the genu, splenium and body of the corpus callosum and that left-greater-than-right asymmetry exists in the anterior limb of the external capsule and in the posterior limb of the internal capsule, thalamus, cerebral peduncle and temporal-parietal regions. VBA of the hemispheric asymmetry of the middle-age group revealed much less asymmetry. Regions showing age-related changes and hemispheric asymmetry from VBA were, for a majority of the findings, in conformance with ROI analysis and with the known pattern of development and age-related degradation of fiber tracks. The study shows the feasibility of the VBA of DTI indices for exploratory investigations of subtle differences in population cohorts, especially when findings are not localized and/or known a priori.

Morphology, localization and accumulation of in vivo microdamage in human cortical bone

In vivo, microdamage occurs in the form of linear microcracks and diffuse damage. However, it is unknown whether the age-related changes in bone quality predispose bone to form one type of damage morphology over the other during in vivo loading. In this study, histological and histomorphometrical analyses were conducted on transverse cross sections, obtained from the tibiae of aging human bone (age 19 to 89), to investigate the in vivo accumulation and localization of damage morphologies. The results demonstrate that old donor bone (83 ± 3 years) contains more linear microcracks than younger donor bone in the cortices predominantly subjected to compressive ( p < 0.01) and tensile loading ( p < 0.01). In contrast, young donor bone (40 ± 10 years) contains more diffuse damage than older donor bone in the cortex predominantly subjected to tensile loading ( p < 0.01). The formation of damage morphology showed no correlation with bone geometry parameters and exhibited distinct preferences with bone microstructure. Linear microcracks formed in the interstitial bone ( p < 0.01) and were either trapped or arrested by the microstructural interfaces (cement line and lamellar interface) ( p < 0.05). Areas of diffuse damage, however, were preferentially associated with secondary osteonal bone ( p < 0.01) and had no relationship with the microstructural interfaces ( p < 0.01). Based upon these findings, we conclude that age-related changes in bone microstructure, but not bone geometry, play a key role in the propensity of old donors to form linear microcrack over diffuse damage under in vivo loading conditions.

Age-related changes in trabecular bone microstructures: global and local morphometry

A recently developed method allows investigating trabecular bone on an elemental (rod/plate) level. With this method, it is possible to measure local morphometric parameters such as thickness or orientation directly on the extracted rods and plates. Age-related changes of trabecular microarchitecture can thus be investigated on an elemental level, which may help to improve the understanding of age-related bone failure mechanism as well as the effect of pharmaceutical intervention in the prevention of such fractures. Autopsies from femoral heads (FH) and lumbar spine (LS) were analyzed by global morphometry. Additionally, the trabecular structures were decomposed into rods and plates for the analysis with local morphometry. These morphometric indices were related to age using an analysis of covariance to test for gender differences and linearity with age. In this study, age-related changes showed no gender but site differences. In LS, rods were thinned in aging and finally vanish from the structure, causing a transformation of the trabecular bone structure to longer and, on average, thicker rods. In FH, changes were expressed by a simultaneous thinning and loss of interconnecting trabeculae and perforation of plates leading to new plates and rods. Results were mostly in agreement with earlier findings using descriptive analysis of the aging process. Here we present for the first time preliminary quantitative evidence of changes in the local microstructure, i.e., individual rods and plates. Nevertheless, the number of samples was too small to make for ready conclusions. We conclude that the combination of local and global morphometry is a useful method for a detailed and quantitative description of age-related changes in bone microstructure.

Quantitative MRI

The advent of MRI has made a remarkable progress in the understanding of age-related brain changes providing a noninvasive tool to study in vivo the normally aging individuals at multiple time points. However, conventional MRI techniques are unable to detect and quantify age-related microstructural changes that have been documented at the post-mortem examination of brain tissues. More sophisticated, quantitative MR techniques such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy have been shown to be sensitive to microstructural and metabolic changes that occur in gray and white matter over the course of life span. This review highlights some of these innovative, quantitative MR techniques that are particularly relevant for the study of occult age-related brain tissue changes. Characterization of the in vivo patterns of molecular and cellular changes that occur in the normal aging brain is of crucial importance to understand the pathophysiology of normal cognitive decline and to interpret observed changes in neurodegenerative diseases.

Zone-dependent changes in human vertebral trabecular bone: clinical implications

We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body—the central third vs. the areas adjacent to the endplates. The aim of the present study was, therefore, to investigate whether such zone-specific differences could be identified by static histomorphometric measures. The material comprised 48 individuals (24 women aged 19–97 years, and 24 men aged 23–95 years). Three of the women had a known fracture of the L-2. From each L-2, thick frontal sections of half of the vertebra were embedded undecalcified in methylmethacrylate, cut into 10-μm-thick sections, and stained with aniline blue. The sections were scanned into a computer, and classic static histomorphometry was performed on the images. The histomorphometry was performed on both the whole section and on the separate zones (central and sub-endplate zone). The results showed that trabecular bone volume, trabecular number, and connectivity density decreased significantly faster with age, whereas marrow space star volume increased significantly faster with age in the zones adjacent to the endplates than in the central zone. The other histomorphometric measures showed no zone specificity in relation to aging. However, trabecular thickness and trabecular separation were both higher at all ages in the central zone than in the sub-endplate zone, although this was significant only for trabecular separation. The described differences might have significant clinical implications concerning quantitative computed tomography (QCT) scanning, X-ray analyses, and assessment of fracture liability in the human spine, but the underlying pathogenesis is still not known. This study shows that the human vertebral body can be described as two distinct zones with very specific age-related changes in density and microstructure. This zone-specificity is important for the correct interpretation of clinical data.

Modeling the mechanical behavior of vertebral trabecular bone: Effects of age-related changes in microstructure

Age-related reductions in the thickness and number of trabeculae in vertebral trabecular bone have been documented by several workers, yet the relative effects of these changes on mechanical properties are not known. We developed a two-dimensional model of human vertebral trabecular bone and investigated its mechanical behavior using finite element analysis. The stress-strain behavior, failure mode, and strain distributions predicted using the model were consistent with those observed for vertebral trabecular bone under compressive loading. Random reductions in the number of trabeculae reduced the modulus and strength of the models two to five times more than uniform reductions in the thickness of trabeculae that caused the same loss of bone volume. For example, randomly removing longitudinal trabeculae to achieve a reduction in density of 10% reduced the strength by approximately 70%, whereas removing the same amount of bone by uniformly reducing the thickness of the longitudinal trabeculae only reduced the strength by approximately 20%. For a simulation of aged bone, in which the thickness and number of trabeculae were reduced concurrently, the strength was 23% of its intact (“young”) value. When the bone mass of the aged model was restored to its intact level by increasing the thickness but not the number of trabeculae, the strength increased by 60%, but was still only 37% of its intact value. These combined findings, based on a two-dimensional, idealized model of vertebral trabecular bone, illustrate the importance of maintaining trabecular number and suggest that it may not be possible to restore bone strength following a period of advanced bone loss if a substantial number of trabeculae have been resorbed. Thus, until treatments exist that can increase trabecular number, the most effective treatment strategy is to prevent the degradation of bone strength by maintaining the number of trabeculae at a healthy level.

Age-related structural changes in the rat cerebellar cortex: Effect of choline alfoscerate treatment

The influence of ageing and of 3 months choline alfoscerate treatment on age-related microstructural changes in cerebellar cortex was studied in 3-, 12- and 24-month-old male Sprague- Dawley rats. The number of Purkinje and granule neurons, the density of Nissl bodies in the cytoplasm of Purkinje and granule neurons and the density of silver-gold impregnated fibres within molecular and granule cells layers were assessed by neurohistological and neurohistochemical techniques associated with microdensitometry and quantitative image analysis. The number of Purkinje and granule neurons was approximately the same in rats of 3 and 12 months and significantly decreased in 24-month-old animals. The density of Nissl bodies and of fine processes of silver-gold impregnated fibres were greatest in the cerebellar cortex of rats of 12 months of age, followed in descending order by 3- and 24-month-old rats. Both the density of Nissl bodies and of silver-gold impregnated fibres were significantly lower in the cerebellar cortex of the oldest age group considered in comparison with the young and middle age groups. Treatment with choline alfoscerate, a precursor in the biosynthesis of brain phospholipids which increases bioavailability of choline in the nervous tissue, noticeably reduced the loss of Purkinje and granule neurons in rats of 24 months. Moreover, it restored the density of Nissl bodies in the cytoplasm of Purkinje and granule neurons as well as the density of silver-gold stained fibres in the molecular and in the granule cells layers to values not significantly different from those found in rats of 3 months.