Regional Age-related Changes Research Articles

Regional age-related changes of neuromelanin and iron in the substantia nigra based on neuromelanin accumulation and iron deposition.

To investigate age-related neuromelanin signal variation and iron content changes in the subregions of substantia nigra (SN) using magnetization transfer contrast neuromelanin-sensitive multi-echo fast field echo sequence in a normal population. In this prospective study, 115 healthy volunteers between 20 and 86years of age were recruited and scanned using 3.0-T MRI. We manually delineated neuromelanin accumulation and iron deposition regions in neuromelanin image and quantitative susceptibility mapping, respectively. We calculated the overlap region using the two measurements mentioned above. Partial correlation analysis was used to evaluate the correlations between volume, contrast ratio (CR), susceptibility of three subregions of SN, and age. Curve estimation models were used to find the best regression model. CR increased with age (r = 0.379, p < 0.001; r = 0.371, p < 0.001), while volume showed an age-related decline (r = -0.559, p < 0.001; r = -0.410, p < 0.001) in the neuromelanin accumulation and overlap regions. Cubic polynomial regression analysis found a small increase in neuromelanin accumulation volume with age until 34, followed by a significant decrease until the 80s (R2 = 0.358, p < 0.001). No significant correlations were found between susceptibility and age in any subregion. No correlation was found between CR and susceptibility in the overlap region. Our results indicated that CR increased with age, while volume showed an age-related decline in the overlap region. We further found that the neuromelanin accumulation region volume increased until the 30s and decreased into the 80s. This study may provide a reference for future neurodegenerative elucidations of substantia nigra. • Our results define the regional changes in neuromelanin and iron in the substantia nigra with age in the normal population, especially in the overlap region. • The contrast ratio increased with age in the neuromelanin accumulation and overlap regions, and volume showed an age-related decline, while contrast ratio and volume do not affect each other indirectly. • The contrast ratio of hyperintense neuromelanin in the overlap region was unaffected by iron content.

Longitudinal increases of brain metabolite levels in 5-10 year old children.

Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies reveal significant changes in brain structure and structural networks that occur together with cognitive and behavioral maturation in childhood. However, the underlying cellular changes accompanying brain maturation are less understood. Examining regional age-related changes in metabolite levels provides insight into the physiology of neurodevelopment. Magnetic resonance spectroscopy (MRS) measures localize brain metabolism. The majority of neuroimaging studies of healthy development are from the developed world. In a longitudinal MRS study of 64 South African children aged 5 to 10 years old (29 female; 29 HIV exposed, uninfected), we examined the age-related trajectories of creatine (Cr+PCr), N-acetyl-aspartate (NAA), the combined NAA+N-acetyl-aspartyl-glutamate (NAAG), choline (GPC+PCh), glutamate (Glu) and the combined Glu+glutamine (Glu+Gln) in voxels within gray and white matter, as well as subcortically in the basal ganglia (BG). In frontal gray matter, we found age-related increases in Cr+PCr, NAA, NAA+NAAG and Glu+Gln levels pointing to synaptic activity likely related to learning. In the BG we observed increased levels of Glu, Glu+Gln and NAA+NAAG with age that point to subcortical synaptic reorganization. In white matter, we found increased levels of Cr+PCr, NAA, NAA+NAAG, Glu and Glu+Gln with age, implicating these metabolites in ongoing myelination. We observed no sex-age or HIV exposure-age interactions, indicating that physiological changes are independent of sex during this time period. The metabolite trajectories presented, therefore, provide a critical benchmark of normal cellular growth for a low socioeconomic pediatric population in the developing world against which pathology and abnormal development may be compared.

Distribution of Cortical Benzodiazepine Receptor Binding in Right-Handed Healthy Humans: A Voxel-Based Statistical Analysis of Iodine 123 Iomazenil SPECT with Partial Volume Correction

CBR imaging is highly susceptible to a PVE produced by morphologic changes in the brain related to aging and brain laterality. We assessed the influence of PVE produced by regional age-related changes in gray matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in human CBR binding by using PVE-corrected SPECT images. Nineteen right-handed healthy volunteers (range, 25-82 years; mean, 55 ± 21 years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The influence of age-related changes in rGMC on SPECT images before PVE correction was assessed. PVE correction of the SPECT images was performed by using an MR imaging-based method. Voxel-based linear regression analyses of the PVE-corrected SPECT images were performed by using SPM5. The age-related reductions in rGMC and BP without PVE correction revealed a significant direct proportional correlation. Voxel-based statistical analysis with PVE correction showed no significant age-related changes in BP. PVE correction was indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR binding in right-handed healthy humans.

Differential Prefrontal White Matter Development in Chimpanzees and Humans

A comparison of developmental patterns of white matter (WM) within the prefrontal region between humans and nonhuman primates is key to understanding human brain evolution. WM mediates complex cognitive processes and has reciprocal connections with posterior processing regions [1, 2]. Although the developmental pattern of prefrontal WM in macaques differs markedly from that in humans [3], this has not been explored in our closest evolutionary relative, the chimpanzee. The present longitudinal study of magnetic resonance imaging scans demonstrated that the prefrontal WM volume in chimpanzees was immature and had not reached the adult value during prepuberty, as observed in humans but not in macaques. However, the rate of prefrontal WM volume increase during infancy was slower in chimpanzees than in humans. These results suggest that a less mature and more protracted elaboration of neuronal connections in the prefrontal portion of the developing brain existed in the last common ancestor of chimpanzees and humans, and that this served to enhance the impact of postnatal experiences on neuronal connectivity. Furthermore, the rapid development of the human prefrontal WM during infancy may help the development of complex social interactions, as well as the acquisition of experience-dependent knowledge and skills to shape neuronal connectivity.

Structural organization of the prefrontal white matter pathways in the adult and aging brain measured by diffusion tensor imaging

Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of frontal callosal fibers to normal aging. The present study extended this examination systematically to other prefrontal white matter regions. Structural magnetic resonance imaging and DTI datasets were acquired from 69 healthy subjects aged 22-84 years. The prefrontal white matter was parcellated into several anatomical sub-regions: medial and lateral orbitofrontal white matter, dorsolateral prefrontal white matter, and medial prefrontal white matter, using reliable DTI-tractography protocols. Tract-specific characteristics were calculated using Matlab. Regression models were used to determine the relationship between age and structural integrity of white matter tracts. The results of our study demonstrate regional age-related changes in the prefrontal white matter tracts of the human brain. This study was cross-sectional and therefore additional longitudinal studies are needed to confirm our findings.

Effects of childhood absence epilepsy on associations between regional cortical morphometry and aging and cognitive abilities

In this study, we used surface-based morphometry to examine whether age-related changes in gray matter tissue thickness and depth of sulcal regions at high spatial resolution across the cortex differed in children with childhood absence epilepsy (CAE) compared to healthy control subjects. In addition, the possibility of variable brain-cognition relationships in the CAE compared to the control group was investigated. The main findings of this study are as follows: (1) From the developmental perspective, children with CAE did not demonstrate the normal regional age-related changes involving a decrease in cortical thickness and increase in sulcal depth. (2) None of the seizure variables, including age of onset, seizure frequency, and AEDs had a significant effect on the association between age and cortical morphometry measures in the CAE population. (3) Even though the CAE group had mean VIQ and PIQ scores in the average range, our findings suggest that they use different brain regions to perform these cognitive functions compared to healthy controls. This first study on brain morphometry and cognition in children with childhood absence seizures has important implications for advancing our understanding of brain development and cognitive comorbidity in CAE, as well as for revisiting the clinical notion that CAE is a benign disorder.

Regional Age-Related Changes in Aortic Pulse Wave Velocity and Systolic Diameter Measured Using Magnetic Resonance Imaging

Regional Age-Related Changes in Aortic Pulse Wave Velocity and Systolic Diameter Measured Using Magnetic Resonance Imaging

Conventional, Diffusion and Magnetization Transfer MRI in the Study of Myelination

Myelination of the brain starts at the second trimester of gestation and continues throughout life. Post mortem studies have demonstrated that myelination continues into the second to third decade of life. It follows a caudal to rostral and a posterior to anterior pattern and proceeds rapidly up to two years of age. Cranial nerves are the first to myelinate, while myelination of white matter tracts carrying sensory information precede to those carrying information relating to movement. The myelination process affects dramatically tissue contrast and changes in the MR appearance of the developing brain have been described initially in conventional sequences. These sequences offer anatomic information and assess macroscopic structural changes of the brain. With the larger application of Diffusion and Magnetization Transfer imaging, a semiquantitative evaluation of the myelination process has been performed and regional age related changes of the mean diffusivity (MD), the apparent diffusion coefficient (ADC), the fractional anisotropy (FA) and the magnetization transfer ratio (MTR) of developing brain have been described. These techniques assess microstructural changes of the brain.

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.

Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain

BackgroundNitric oxide (NO) is a multifunctional molecule synthesized by three isozymes of the NO synthase (NOSs) acting as a messenger/modulator and/or a potential neurotoxin. In rodents, the role of NOSs in sleep processes and throughout aging is now well established. For example, sleep parameters are highly deteriorated in senescence accelerated-prone 8 (SAMP8) mice, a useful animal model to study aging or age-associated disorders, while the inducible form of NOS (iNOS) is down-regulated within the cortex and the sleep-structures of the brainstem. Evidence is now increasing for a role of iNOS and resulting oxidative stress but not for the constitutive expressed isozyme (nNOS). To better understand the role of nNOS in the behavioural impairments observed in SAMP8 versus SAMR1 (control) animals, we evaluated age-related variations occurring in the nNOS expression and activity and nitrites/nitrates (NOx-) levels, in three brain areas (n = 7 animals in each group). Calibrated reverse transcriptase (RT) and real-time polymerase chain reaction (PCR) and biochemical procedures were used.ResultsWe found that the levels of nNOS mRNA decreased in the cortex and the hippocampus of 8- vs 2-month-old animals followed by an increase in 12-vs 8-month-old animals in both strains. In the brainstem, levels of nNOS mRNA decreased in an age-dependent manner in SAMP8, but not in SAMR1. Regional age-related changes were also observed in nNOS activity. Moreover, nNOS activity in hippocampus was found lower in 8-month-old SAMP8 than in SAMR1, while in the cortex and the brainstem, nNOS activities increased at 8 months and afterward decreased with age in SAMP8 and SAMR1. NOx- levels showed profiles similar to nNOS activities in the cortex and the brainstem but were undetectable in the hippocampus of SAMP8 and SAMR1. Finally, NOx- levels were higher in the cortex of 8 month-old SAMP8 than in age-matched SAMR1.ConclusionConcomitant variations occurring in NO levels derived from nNOS and iNOS at an early age constitute a major factor of risk for sleep and/or memory impairments in SAMP8.

Determination of age at death using combined morphology and histology of the femur.

Bone is characterised by age-related morphological and histological changes. We have previously established an automated method of recording bone morphometry and histology from entire transverse sections of cortical bone. Our aim was to determine whether data acquired using this automated system were useful in the prediction of age. Ninety-six specimens of human femoral middiaphysis were studied from subjects aged 21-92 y. Equations predicting specimen age were constructed using macroscopic data (total subperiosteal area (TSPA), periosteal perimeter (PP), endosteal perimeter (EP), cortical bone area (CA) and moments of area) and microscopic data (the number, size and diversity of pores and intracortical porosity) together with sex, height and weight. Both TSPA and PP were independent predictors of age but the number of pores was not a significant predictor of age in any equation. The age predicted by these equations was inaccurate by more than 8 y in over half the subjects. We conclude that we could not predict age at a clinically acceptable level using data from our automated system. This most likely reflects an insensitivity to regional age-related changes in bone histology because we recorded data from each entire cortex. Automated bone measurement according to cortical region might be more useful in the prediction of age. The inclusion of TSPA together with PP as independent predictors of age raises the possibility that a future measure of periosteal shape at the femoral diaphysis could also be helpful in the prediction of age. The accuracy reached with the relatively simple methods described here is sufficient to encourage the development of image-analysis systems for the automatic detection of more complex features.

Effect of vinconate against regional age-related changes in the gerbil brain

We investigated age-related changes in the binding sites of muscarinic acetylcholine, forskolin, adenosine 3', 5' -cyclic monophosphatee (cAMP), and of a voltage-dependent L-type calcium channel blocker in the gerbil brain receptor autoradiography. [ 3H]Quinuclidinyl benzilate (QNB), [ 3H]forskolin, [ 3H]cAMP, and [ 3H]PN200-110 were used to label muscarinic receptors, adenylate cyclase, cAMP-dependent protein kinase, and L-type calcium channels, respectively. In middle-aged animals (16-month-old gerbils), [ 3H]QNB, [ 3H]PN200-110, [ 3H]forskolin, and [ 3H]cAMP binding sites were elevated in the hippocampal region compared with that of young gerbils (4 weeks old). Further, a significant elevation in [ 3H]forskolin binding was seen in the nucleus accumbens. In contrast, [ 3H]QNB, [ 3H]PN200-110, and [ 3H]forskolin binding sites were reduced in the cerebellum, neocortex and thalamus, and hypothalamus in middle-aged animals, respectively, [ 3H]cAMP binding was not altered in other regions except for an elevation in the hippocampus. Thus, the age-related alterations in receptor binding may proceed by different mechanisms in various brain regions. Chromic vinconate treatment partly modulated the age-related alterations in [ 3H]QNB, [ 3H]forskolin, and [ 3H]cAMP binding in the hippocampus, but not that of [ 3H]PN200-110. Vinconate also regulated the age-related changes in [ 3H]forskolin binding in the nucleus accumbens. These results indicate that the age-related alterations in the binding sites of muscarinic acetylcholine, forskolin, cAMP, and L-type calcium channel blocker occur in particular in the hippocampus. Further, they suggest that a novel vince alkaloid derivative, vinconate, can partly modulate age-related changes in the binding sites.

Positron emission tomography studies of normal aging: A replication of PET III and 18-FDG using PET VI and 11-CDG

Using PET VI and 11-CDG we replicated our earlier PET III and 18-FDG normal aging findings. Examination of young and old normal volunteers revealed the absence of any absolute regional age-related changes in glucose utilization. For the combined sample ( N=81) we did find evidence to suggest a relative hypofrontal change with increasing age. A strong relationship between age and ventricular size (CT) was also found. These findings suggest the preserved glucose metabolism of the resting aging brain in the presence of structural atrophic changes.