MTR
Methionine synthase (EC 2.1.1.13) (MS) (5-methyltetrahydrofolate--homocysteine methyltransferase) (Cobalamin-dependent methionine synthase) (Vitamin-B12 dependent methionine synthase)
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We examined the effect of age and training status on the oxygen uptake (V˙ O ) kinetics of untrained and recreationally trained women. Young (20-35yr), middle-age (40-55yr) and older (58-71yr) recreationally trained (YTR, n = 10; MTR, n = 12; OTR, n = 9) and untrained (YUT, n = 12; MUT, n = 10; OUT, n = 9) women participated in this crossectional study. Breath-by-breath V˙ O and near-infrared-spectroscopy-derived (NIRS) muscle deoxygenation [HHb] were monitored continuously during increasing and constant walking exercises. On-transition V˙ O and [HHb] responses to moderate intensity walking were modeled as mono-exponential. The data were normalized for each subject (0%-100 %), and [HHb]/ V˙ O ratio was calculated as the average [HHb]/ V˙ O during the 20- to 120-s period after the onset of moderate intensity walking exercise. The time constant of V˙ O (τ V˙ O ) was longer in OUT(23.8 ± 2.4), MUT(25.4 ± 5.1), YUT(23.1 ± 3.4) than in YTR(16.2 ± 2.0), MTR(16.7 ± 3.9), OTR(16.3 ± 2.8) women (p < 0.05). The [HHb]/ V˙ O ratio in OUT (1.31 ± 0.18) was higher than in YTR(1.08 ± 0.05), MTR(1.13 ± 0.09), YUT(1.12 ± 0.09) (p < 0.05). It is concluded that recreationally trained women had faster V˙ O kinetics along with better matching of O delivery and utilization at the site of gas exchange in the exercising muscles.
Keywords
- Aging
- Muscle deoxygenation
- Oxygen uptake kinetic
- Recreationally trained
- Women
Amide proton transfer-weighted (APTw) imaging has been revealed to hold great potential in the diagnosis of several brain diseases. The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw magnetic resonance imaging (MRI) in characterizing normal brain aging. A total of 106 healthy subjects were recruited and scanned at 3.0 Tesla, with APTw and conventional magnetization transfer (MT) sequences. Quantitative image analyses were performed in 12 regions of interest (ROIs) for each subject. The APTw or MT ratio (MTR) signal differences among five age groups (young, mature, middle-aged, young-old, and middle-old) were assessed using the one-way analysis of variance, with the Benjamini-Hochberg correction for multiple comparisons. The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression. There were no significant differences between the APTw or MTR values for males and females in any of the 12 ROIs analyzed. Among the five age groups, there were significant differences in the three white matter regions in the temporal, occipital, and frontal lobes. Overall, the mean APTw values in the older group were higher than those in the younger group. Positive correlations were observed in relation to age in most brain regions, including four with significant positive correlations (r=0.2065-0.4182) and five with increasing trends. As a comparison, the mean MTR values did not appear to be significantly different among the five age groups. In addition, the mean APTw and MTR values revealed significant positive correlations in 10 ROIs (r=0.2214-0.7269) and a significant negative correlation in one ROI (entorhinal cortex, r=-0.2141). Our early results show that the APTw signal can be used as a promising and complementary imaging biomarker with which normal brain aging can be evaluated at the molecular level.
Keywords
- Aging
- amide proton transfer imaging
- biomarkers
- chemical exchange saturation transfer (CEST)
- molecular imaging
The sex-specific link between longitudinal annual rate of cognitive change (LARCC) and polymorphisms in one-carbon metabolism enzymatic genes remains unclear, particularly among African-American adults. We tested associations of 14 single nucleotide polymorphisms (SNPs) from MTHFR, MTRR, MTR, and SHMT genes and select MTHFR haplotypes and latent classes (SNPHAP/SNPLC) with LARCC. Up to 797 African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (age: 30-64 y, 52% women) had 1.6-1.7 (i.e., 1 or 2) repeated measures (follow-up time, mean = 4.69 y) on 9 cognitive test scores, reflecting verbal and visual memory, verbal fluency, psychomotor speed, attention, and executive function: California Verbal Learning Test-immediate recall (CVLT-List A), CVLT-DFR (delayed free recall), Benton Visual Retention Test (BVRT), Animal Fluency (AF), Digits Span Forward and Backward tests, and Trail Making Test parts A and B (Trails A and B). Multiple linear mixed-effects and multiple linear regression models were conducted. Overall, MTHFR SNPs rs4846051(A1317G, G>A) and rs1801131(A1298C, G>T) were associated with slower and faster declines on AF, respectively, whereas rs2066462(C1056T, A>G) was related to slower decline on Trails B (executive function). Among men, rs4846051(A1317G, G>A) was linked to faster decline on BVRT (visual memory), whereas rs2066462(C1056T, A>G) and rs9651118(C>T) were associated with slower decline on CVLT-List A and rs9651118(C>T) with faster decline on CVLT-DFR. Among women, a slower decline on the domain "verbal memory/fluency" was observed with rs1801133(C677T, A>G). MTHFR SNPHAP [rs1801133(C677T, A>G)/rs1801131(A1298C, G>T): GG] was associated with slower decline on AF among women, whereas MTHFR SNPHAP(AT) was linked with slower decline on CVLT-List A among men but faster decline on "verbal memory/fluency" among women. Similar patterns were observed for MTHFR SNPLCs. In sum, MTHFR gene variations can differentially impact longitudinal changes in multiple cognitive domains among African-American adults.
MeSH Terms
- African Americans
- Carbon
- Cognitive Dysfunction
- Humans
- Polymorphism, Genetic
Keywords
- Aging
- Cognitive change
- Genetic polymorphisms
- Haplotypes
- MTHFR
- One-carbon metabolism
To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV). Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies.
MeSH Terms
- Adult
- Aged
- Aging
- Female
- Humans
- Male
- Middle Aged
- Myelin Sheath
- Reproducibility of Results
- Spinal Cord
- Young Adult
Successfully switching between tasks is critical in many daily activities. Age-related slowing of this switching behavior has been documented extensively, but the underlying neural mechanisms remain unclear. Here, we investigated the contribution of brain white matter changes associated with myelin alterations to age-related slowing of switching performance. Diffusion tensor imaging derived radial diffusivity (RD) and magnetization transfer imaging derived magnetization transfer ratio (MTR) were selected as myelin sensitive measures. These metrics were studied in relation to mixing cost (i.e., the increase in reaction time during task blocks that require task switching) on a local-global switching task in young (n = 24) and older (n = 22) adults. Results showed that higher age was associated with widespread increases in RD and decreases in MTR, indicative of white matter deterioration, possibly due to demyelination. Older adults also showed a higher mixing cost, implying slowing of switching performance. Finally, mediation analyses demonstrated that decreases in MTR of the bilateral superior corona radiata contributed to the observed slowing of switching performance with increasing age. These findings provide evidence for a role of cortico-subcortical white matter changes in task switching performance deterioration with healthy aging. Hum Brain Mapp 37:4084-4098, 2016. © 2016 Wiley Periodicals, Inc.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Brain
- Diffusion Tensor Imaging
- Executive Function
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Neuropsychological Tests
- Reaction Time
- White Matter
- Young Adult
Keywords
- aging
- diffusion tensor imaging
- magnetization transfer imaging
- mediation
- mixing cost
- switch cost
Superficial white matter (SWM) lies immediately beneath cortical gray matter and consists primarily of short association fibers. The characteristics of SWM and its development and aging were seldom examined in the literature and warrant further investigation. Magnetization transfer imaging is sensitive to myelin changes in the white matter. Using an innovative multimodal imaging analysis approach, vertex-based surface statistics (VBSS), the current study vertexwise mapped age-related changes of magnetization transfer ratio (MTR) in SWM from young adulthood to old age (30-85 years, N = 66). Results demonstrated regionally selective and temporally heterochronologic changes of SWM MTR with age, including (1) inverted U-shaped trajectories of SWM MTR in the rostral middle frontal, medial temporal, and temporoparietal regions, suggesting continuing myelination and protracted maturation till age 40-50 years and accelerating demyelination at age 60 and beyond, (2) linear decline of SWM MTR in the middle and superior temporal, and pericalcarine areas, indicating early maturation and less acceleration in age-related degeneration, and (3) no significant changes of SWM MTR in the primary motor, somatosensory and auditory regions, suggesting resistance to age-related deterioration. We did not observe similar patterns of changes in cortical thickness in our sample, suggesting the observed SWM MTR changes are not due to cortical atrophy. Hum Brain Mapp 37:1759-1769, 2016. © 2016 Wiley Periodicals, Inc.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Brain Mapping
- Female
- Healthy Volunteers
- Humans
- Image Processing, Computer-Assisted
- Linear Models
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Myelin Sheath
- White Matter
Keywords
- cortical thickness
- development and aging
- magnetization transfer
- myelin
- white matter
The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Cell Differentiation
- Cells, Cultured
- Collagen
- Immunoenzyme Techniques
- Male
- Patellar Ligament
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Running
- Stem Cells
- Stress, Mechanical
- Tendon Injuries
- Wound Healing
Keywords
- Gerotarget
- aging rat
- proliferation
- tendon stem cell
- treadmill running
- wound healing
Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits.
MeSH Terms
- Aging
- Anthropometry
- Bayes Theorem
- Cardiovascular Diseases
- Diet
- Energy Metabolism
- Feeding Behavior
- Female
- Genetic Predisposition to Disease
- Humans
- Life Style
- Lipid Metabolism
- Lipoproteins, LDL
- Male
- Middle Aged
- Risk Factors
- Turkey
- Waist-Hip Ratio
Keywords
- Cardiometabolic traits
- Diet
- Genetic predisposition
- Interactive mechanisms
- Turkey
In the last decade, several studies have described the typical brain white matter maturation in children and adolescents. Diffusion tensor imaging (DTI) is the most frequent MRI technique used to investigate the structural changes across development. However, few previous studies have used the magnetization transfer ratio (MTR), which gives a closer measure of myelin content. Here, we employed both techniques for the same sample of 176 typically developing children from 7 to 14years of age. We investigated the associations between DTI parameters and MTR measure, to assess the myelination in the brain in development. Secondly, we investigated age-effects on DTI parameters (fractional anisotropy, axial, radial and mean diffusivities) and MTR. No significant correlations between MTR and DTI parameters were observed. In addition, a significant age-effect was detected for DTI data but was not visible for MTR data. Thereby, changes in white matter at this age might be primarily correlated with microstructural changes.
MeSH Terms
- Adolescent
- Adolescent Development
- Aging
- Anisotropy
- Child
- Child Development
- Diffusion Tensor Imaging
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Myelin Sheath
- White Matter
Keywords
- Adolescence
- Childhood
- Diffusion tensor imaging
- Magnetization transfer ratio
- Normal brain development
Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (≤65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.
Keywords
- Magnetic Resonance Imaging (MRI)
- Magnetization Transfer Imaging (MTI)
- age
- brain
- familial longevity
- glucose
- insulin
This study aimed to investigate whether magnetization transfer imaging (MTI) parameters of cortical gray and white matter and subcortical gray matter structures differ between subjects enriched for human familial longevity and control subjects to provide a thorough description of the brain phenotype of familial longevity. Moreover, we aimed to describe cerebral ageing effects on MTI parameters in an elderly cohort. All subjects were included from the Leiden Longevity Study and underwent 3 Tesla MTI of the brain. In total, 183 offspring of nonagenarian siblings, who are enriched for familial factors of longevity, were contrasted with 163 environmentally and age-matched controls. No differences in cortical and subcortical gray matter and white matter MTI parameters were found between offspring and control subjects using histogram-based and voxel-wise analyses. Cortical gray matter and white matter MTI parameters decreased with increasing chronological age (all p < 0.001). Decrease of white matter magnetization transfer ratio (MTR) was homogeneous throughout the whole mean white matter skeleton except for parts of the callosal splenium and partly the posterior limb of the internal capsule and superior region of the corona radiata (p < 0.05). Mean MTR of subcortical gray matter structures decreased with increasing age (p amygdala, caudate nucleus and putamen < 0.001; p pallidum = 0.001, p thalamus = 0.002). In conclusion, the brain phenotype of human familial longevity is - at a mean age of 66 years - not characterized by preserved macromolecular brain tissue integrity.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Brain
- Brain Mapping
- Cohort Studies
- Female
- Gray Matter
- Humans
- Longevity
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Phenotype
- Radiography
- White Matter
White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.
MeSH Terms
- Aged
- Aging
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- White Matter
Keywords
- Aging
- Multimodal MRI
- Normal-appearing white matter
- White matter hyperintensities
Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern.
MeSH Terms
- Aged
- Aging
- Algorithms
- Alzheimer Disease
- Case-Control Studies
- Demyelinating Diseases
- Female
- Humans
- Limbic Lobe
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Myelin Sheath
- Severity of Illness Index
- Temporal Lobe
- White Matter
Keywords
- Connectivity
- U-fibers
- graph theory
- interhemispheric asymmetry
- magnetization transfer imaging
Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38-86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.
Keywords
- cerebrovascular disease
- cognitive aging
- dementia
- magnetic resonance imaging
- magnetization transfer imaging
- microstructural tissue damage
To explore gender, age-related, and regional differences of magnetization transfer ratio (MTR) of brain cortical and subcortical gray matter (GM). In all, 102 healthy subjects (51 women and 51 men; range 25-84 years) were examined with 3-mm thick MT images. We assessed MTR in automatically segmented GM structures including frontal, parietal-insular, temporal, and occipital cortex, caudate, pallidus and putamen, and cerebellar cortex. A general linear model analysis was conducted to ascertain the linear and quadratic relationship among the MTR and gender, age, and anatomical structure. The effect of gender was borderline (P = 0.07) in all GM structures (with higher MTR values in men), whereas age showed a significant linear as well as quadratic effect in all cortical and subcortical GM structures (P ≤ 0.001). Quadratic age-related decrease in MTR began at about 40 years of age. Mean and standard deviation (SD) of MTR had the following decreasing order: thalamus (58.3 0.8), pallidus (56.8 ± 1.3), caudate (55.5 ± 1.6) and putamen (54.6 ± 1.1); temporal (56.8 ± 0.9), parietal-insular (56.8 ± 1.1), frontal (56.5 ± 1.1), occipital (55.4 ± 1.0) and cerebellar (53.2 ± 1.0) cortex. In post-hoc testing, all regional pairwise differences were statistically significant except pallidus vs. temporal or parietal-insular cortex, caudate vs. occipital cortex, frontal vs. parietal-insular or temporal cortex. MTR of the cortical and subcortical brain GM structures decreases quadratically after midlife and shows significant regional differences.
MeSH Terms
- Adult
- Aged
- Aging
- Brain
- Female
- Gray Matter
- Humans
- Image Interpretation, Computer-Assisted
- Magnetic Fields
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Reference Values
- Reproducibility of Results
- Sensitivity and Specificity
- Sex Characteristics
Keywords
- aging
- automatic segmentation
- gray matter
- magnetization transfer
Multiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration. To determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI. Forty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region. All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes. Despite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.
MeSH Terms
- Adult
- Age Factors
- Aging
- Brain
- Disability Evaluation
- Female
- Humans
- Imaging, Three-Dimensional
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Multiple Sclerosis
- Myelin Sheath
- ROC Curve
Keywords
- Aging
- GM, gray matter
- GML, gray matter lesion
- MRI
- MTR, magnetization transfer ratio
- Magnetization transfer
- Multiple sclerosis
- NAGM, normal appearing gray matter
- NAWM, normal appearing white matter
- WM, white matter
- WML, white matter lesion
Magnetization-transfer imaging (MTI), a magnetic resonance imaging acquisition protocol, can detect microstructural brain tissue changes by assessing the magnetization exchange between tissue water and protons bound to macromolecules. This short literature review summarizes results of previous MTI studies in normal aging, cerebral small vessel disease, and Alzheimer's disease (AD). During normal aging, the magnetization transfer ratio (MTR), a measure for the magnitude of magnetization transfer between macromolecular and water protons, declines in normal appearing brain tissue and associations between lower MTR and executive dysfunction have been described. In AD, MTR changes follow a disease-specific temporo-parietal pattern, independent of cortical atrophy. The differential diagnostic contribution beyond atrophy seems to be modest and the independent effect of MTR alterations as predictors of conversion from mild cognitive impairment to AD needs to be explored. MTR correlates well with global cognitive measures like the Mini-Mental State Examination, and MTR decreases rapidly over time in AD. Longitudinal studies are needed to determine the clinical relevance of global and regional MTI measures in normal aging and neurodegenerative disease. Moreover, correlative MTI-histopathologic postmortem studies are warranted to determine the full spectrum of tissue destruction underlying MTR lowering apart from demyelination.
MeSH Terms
- Aging
- Brain
- Dementia
- Humans
- Image Processing, Computer-Assisted
- Longitudinal Studies
- Magnetic Resonance Imaging
- Neuropsychological Tests
Keywords
- Aging
- Alzheimer's disease
- dementia
- magnetic resonance imaging
- magnetization transfer contrast imaging
- mild cognitive impairment
- vascular dementia
Hippocampal structural integrity is commonly quantified using volumetric measurements derived from brain magnetic resonance imaging (MRI). Previously reported associations with cognitive decline have not been consistent. We investigate hippocampal integrity using quantitative MRI techniques and its association with cognitive abilities in older age. Participants from the Lothian Birth Cohort 1936 underwent brain MRI at mean age 73 years. Longitudinal relaxation time (T1), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampus. General factors of fluid-type intelligence (g), cognitive processing speed (speed) and memory were obtained at age 73 years, as well as childhood IQ test results at age 11 years. Amongst 565 older adults, multivariate linear regression showed that, after correcting for ICV, gender and age 11 IQ, larger left hippocampal volume was significantly associated with better memory ability (β = .11, p = .003), but not with speed or g. Using quantitative MRI and after correcting for multiple testing, higher T1 and MD were significantly associated with lower scores of g (β range = -.11 to -.14, p < .001), speed (β range = -.15 to -.20, p < .001) and memory (β range = -.10 to -.12, p < .001). Higher MTR and FA in the hippocampus were also significantly associated with higher scores of g (β range = .17 to .18, p < .0001) and speed (β range = .10 to .15, p < .0001), but not memory. Quantitative multi-modal MRI assessments were more sensitive at detecting cognition-hippocampal integrity associations than volumetric measurements, resulting in stronger associations between MRI biomarkers and age-related cognition changes.
MeSH Terms
- Aged
- Aging
- Cognition
- Female
- Functional Laterality
- Hippocampus
- Humans
- Independent Living
- Intelligence
- Magnetic Resonance Imaging
- Male
- Neuropsychological Tests
Keywords
- Ageing
- Cognition
- Diffusion tensor imaging
- Hippocampus
- Longitudinal relaxation times
- Magnetic resonance imaging
Magnetization transfer imaging detects cerebral microstructural tissue alterations. We examined the association between the Framingham Stroke Risk Profile (FSRP) score and magnetization transfer imaging (MTI) measures in pathological and normal appearing brain tissue in clinically normal elderly subjects to determine if stroke risk leads to brain tissue destruction beyond what is visible in conventional MRI scans. The study cohort is from the Austrian Stroke Prevention Study (ASPS). A total of 316 subjects underwent MTI and had a complete risk factor assessment sufficient to calculate the FSRP score. There were 205 women and 111 men with a mean age of 70.2 years ranging from 54 to 82 years. Subjects were grouped into four categories of stroke risk probability ranging from 3% to 88% for men and 1% to 84% for women. A higher FSRP score was significantly and independently associated with a MTR peak position shift indicating global microstructural alterations in brain tissue (BT) and in normal appearing brain tissue (NABT). The mean MTR in white matter hyperintensities (WMH) correlated inversely with increasing stroke risk. Age explained most of the variance in MTR peak position, all other risk factors of the FSRP score contributed significantly but explained an additional 2% of the variance of this MRI measure, only. Increasing risk for stroke leads to microstructural brain changes invisible by standard MRI. The validity, the underlying pathogenic mechanisms and the clinical importance of these abnormalities needs to be further determined.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Austria
- Brain
- Cerebrovascular Disorders
- Cohort Studies
- Data Interpretation, Statistical
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Regression Analysis
- Risk Factors
- Stroke
Keywords
- Cerebrovascular risk factors
- Magnetic resonance imaging
- Magnetization transfer imaging
- Stroke