Age-related Microstructural Changes Research Articles

White Matter Microstructure of the Genu of the Corpus Callosum Measured Using Neurite Orientation Dispersion and Density Imaging (NODDI) Is Associated with Cardiorespiratory Fitness in Older Adults

Changes in white matter microstructure of the genu of the corpus callosum are predictive of cognitive decline in patients with mild cognitive impairment. Cardiorespiratory fitness (CRF) is positively associated with brain health; however, the relationship between cardiorespiratory fitness and white matter microstructure of the genu of the corpus callosum is unknown. Further, a novel diffusion method for assessing white matter microstructure, neurite orientation dispersion and density imaging (NODDI), can detect specific microstructural features that are not observed with conventional diffusion tensor imaging (DTI). Young (n=27, age=25±5, m=12, f=15) and older (n=23, age=64±5, m=12, f=11) adults free of underlying disease participated in this study. CRF was assessed using an incremental maximal exercise test on a cycle ergometer. On a separate visit, white matter microstructure of the genu of the corpus callosum was measured using both DTI and NODDI MRI scans. In young adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured using either DTI or NODDI (p>0.05). In older adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured with DTI. However, in older adults, there was a positive association between CRF and orientation dispersion index of the genu of the corpus callosum measured with NODDI (r=0.47, p=0.02). In conclusion, using conventional DTI, no associations between CRF and white matter microstructure of the genu of the corpus callosum were observed. However, using NODDI, which can detect specific microstructural features, our results suggest that older adults with higher CRF demonstrated enhanced white matter microstructure, specifically orientation dispersion index, of the genu of the corpus callosum. Conventional DTI may underestimate the impact of CRF on age-related changes in white matter microstructure. National Institutes of Health - HL118154 (JNB), HL007936 (KBM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neuronal microstructural changes in the human brain are associated with neurocognitive aging.

Gray matter (GM) alterations play a role in aging-related disorders like Alzheimer's disease and related dementias, yet MRI studies mainly focus on macroscopic changes. Although reliable indicators of atrophy, morphological metrics like cortical thickness lack the sensitivity to detect early changes preceding visible atrophy. Our study aimed at exploring the potential of diffusion MRI in unveiling sensitive markers of cortical and subcortical age-related microstructural changes and assessing their associations with cognitive and behavioral deficits. We leveraged the Human Connectome Project-Aging cohort that included 707 participants (394 female; median age = 58, range = 36-90 years) and applied the powerful mean apparent diffusion propagator model to measure microstructural parameters, along with comprehensive behavioral and cognitive test scores. Both macro- and microstructural GM characteristics were strongly associated with age, with widespread significant microstructural correlations reflective of cellular morphological changes, reduced cellular density, increased extracellular volume, and increased membrane permeability. Importantly, when correlating MRI and cognitive test scores, our findings revealed no link between macrostructural volumetric changes and neurobehavioral performance. However, we found that cellular and extracellular alterations in cortical and subcortical GM regions were associated with neurobehavioral performance. Based on these findings, it is hypothesized that increased microstructural heterogeneity and decreased neurite orientation dispersion precede macrostructural changes, and that they play an important role in subsequent cognitive decline. These alterations are suggested to be early markers of neurocognitive performance that may distinctly aid in identifying the mechanisms underlying phenotypic aging and subsequent age-related functional decline.

MicroCT imaging of canid diaphyses: bone ontogeny from a zooarchaeological and digital perspective

X-ray microCT offers the possibility of studying the internal structure of animal remains by detecting age-related changes in bone microstructure. In the present work, we analyse developmental patterns of the diaphyseal structure in canids. In particular, the first metacarpal of current and archaeological individuals of red fox (Vulpes vulpes) and wolf (Canis lupus) was analysed. Variables describing bone structure were measured by inferring bone development through the observation of cross-sections. The results show how bone structure changes over the course of a lifetime and how this approach makes it possible to separate young and older individuals. This is important from a zooarchaeological point of view to estimate the age at death of fragmentary animal remains and to discriminate taxa characterised by similar morphology but different adult body size using a non-destructive approach.

Age-related changes in human skeletal muscle microstructure and architecture assessed by diffusion-tensor magnetic resonance imaging and their association with muscle strength.

Diffusion-tensor magnetic resonance imaging (DT-MRI) offers objective measures of muscle characteristics, providing insights into age-related changes. We used DT-MRI to probe skeletal muscle microstructure and architecture in a large healthy-aging cohort, with the aim of characterizing age-related differences and comparing these to muscle strength. We recruited 94 participants (43 female; median age = 56, range = 22-89 years) and measured microstructure parameters-fractional anisotropy (FA) and mean diffusivity (MD)-in 12 thigh muscles, and architecture parameters-pennation angle, fascicle length, fiber curvature, and physiological cross-sectional area (PCSA)-in the rectus femoris (RF) and biceps femoris longus (BFL). Knee extension and flexion torques were also measured for comparison to architecture measures. FA and MD were associated with age (β = 0.33, p = 0.001, R2 = 0.10; and β = -0.36, p < 0.001, R2 = 0.12), and FA was negatively associated with Type I fiber proportions from the literature (β = -0.70, p = 0.024, and R2 = 0.43). Pennation angle, fiber curvature, fascicle length, and PCSA were associated with age in the RF (β = -0.22, 0.26, -0.23, and -0.31, respectively; p < 0.05), while in the BFL only curvature and fascicle length were associated with age (β = 0.36, and -0.40, respectively; p < 0.001). In the RF, pennation angle and PCSA were associated with strength (β = 0.29, and 0.46, respectively; p < 0.01); in the BFL, only PCSA was associated with strength (β = 0.43; p < 0.001). Our results show skeletal muscle architectural changes with aging and intermuscular differences in the microstructure. DT-MRI may prove useful for elucidating muscle changes in the early stages of sarcopenia and monitoring interventions aimed at preventing age-associated microstructural changes in muscle that lead to functional impairment.

Ontogenetic changes in cortical bone vascular microstructure in the domestic duck (Anas platyrhynchos) and ring-necked pheasant (Phasianus colchicus).

Age-related changes in bone microstructure can inform our understanding the biology of both extant and fossil birds, but to date, histological work in birds, and particularly work using high-resolution 3D imaging, has largely been restricted to limited growth stages. We used minimally destructive synchrotron radiation-based X-ray computed tomography to visualise and measure key morphological and histological traits in 3D across development in the domestic duck and ring-necked pheasant. We use these measurements to build on the database of key reference material for interpreting bone histology. We found that growth patterns differed between the two species, with the ducks showing rapid growth in their lower limbs and early lower limb maturation, while pheasants grew more slowly, reflecting their later age at maturity. In the pheasant, both walking and flight occur early and their upper and lower limbs grew at similar rates. In the duck, flight and wing development are delayed until the bird is almost at full body mass. Through juvenile development, the second moment of area for the duck wing was low but increased rapidly towards the age of flight, at which point it became significantly greater than that of the lower limb, or the pheasant. On a microstructural level, both cortical porosity and canal diameter were related to cortical bone deposition rate. In terms of orientation, vascular canals in the bone cortex were more laminar in the humerus and femur compared with the tibiotarsus, and laminarity increased through juvenile development in the humerus, but not the tibiotarsus, possibly reflecting torsional vs compressive loading. These age-related changes in cortical bone vascular microstructure of the domestic duck and pheasant will help understanding the biology of both extant and fossil birds, including age estimation, growth rate and growth patterns, and limb function.

Hypothalamic microstructure and function are related to body mass, but not mental or cognitive abilities across the adult lifespan

Physical, mental, and cognitive resources are essential for healthy aging. Aging impacts on the structural integrity of various brain regions, including the hippocampus. Even though recent rodent studies hint towards a critical role of the hypothalamus, there is limited evidence on functional consequences of age-related changes of this region in humans. Given its central role in metabolic regulation and affective processing and its connections to the hippocampus, it is plausible that hypothalamic integrity and connectivity are associated with functional age-related decline. We used data of n = 369 participants (18–88 years) from the Cambridge Centre for Ageing and Neuroscience repository to determine functional impacts of potential changes in hypothalamic microstructure across the lifespan. First, we identified age-related changes in microstructure as a function of physical, mental, and cognitive health and compared those findings to changes in hippocampal microstructure. Second, we investigated the relationship of hypothalamic microstructure and resting-state functional connectivity and related those changes to age as well as physical health. Our results showed that hypothalamic microstructure is not affected by depressive symptoms (mental health), cognitive performance (cognitive health), and comparatively stable across the lifespan, but affected by body mass (physical health). Furthermore, body mass changes connectivity to limbic regions including the hippocampus, amygdala, and nucleus accumbens, suggesting functional alterations in the metabolic and reward systems. Our results demonstrate that hypothalamic structure and function are affected by body mass, focused on neural density and dispersion, but not inflammation. Still, observed effect sizes were small, encouraging detailed investigations of individual hypothalamic subunits.

3D finite-element brain modeling of lateral ventricular wall loading to rationalize periventricular white matter hyperintensity locations

Aging-related periventricular white matter hyperintensities (pvWMHs) are a common observation in medical images of the aging brain. The underlying tissue damage is part of the complex pathophysiology associated with age-related microstructural changes and cognitive decline. PvWMH formation is linked to blood–brain barrier dysfunction from cerebral small vessel disease as well as the accumulation of cerebrospinal fluid in periventricular tissue due to progressive denudation of the ventricular wall. In need of a unifying theory for pvWMH etiology, image-based finite-element modeling is used to demonstrate that ventricular expansion from age-related cerebral atrophy and hemodynamic loading leads to maximum mechanical loading of the ventricular wall in the same locations that show pvWMHs. Ventricular inflation, induced via pressurization of the ventricular wall, creates significant ventricular wall stretch and stress on the ependymal cells lining the wall, that are linked to cerebrospinal fluid leaking from the lateral ventricles into periventricular white matter tissue. Eight anatomically accurate 3D brain models of cognitively healthy subjects with a wide range of ventricular shapes are created. For all models, our simulations show that mechanomarkers of mechanical wall loading are consistently highest in pvWMHs locations (p < 0.05). Maximum principal strain, the ependymal cell thinning ratio, and wall curvature are on average 14%, 8%, and 24% higher in pvWMH regions compared to the remaining ventricular wall, respectively. Computational modeling provides a powerful framework to systematically study pvWMH formation and growth with the goal to develop pharmacological interventions in the future.

Bone microstructure in healthy men measured by HR-pQCT: Age-related changes and their relationships with DXA parameters and biochemical markers.

The primary purpose of this cross-sectional study was to investigate the characteristics of age-related changes in bone microstructure on high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) on dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers in men. The secondary purpose of this study was to examine how bone microstructure is related to aBMD and biochemical markers. The subjects were 128 healthy Japanese men (20-97years old). Bone microstructure was measured in the distal radius and tibia using second-generation HR-pQCT; aBMD in the proximal femur and lumbar spine was measured with DXA; and tartrate-resistant acid phosphatase-5b (TRACP-5b), type I procollagen-N-propeptide (P1NP), 25(OH) vitamin D, and pentosidine concentrations were measured by blood tests. In trabecular bone, the trabecular volumetric BMD (Tb.vBMD) and trabecular number (Tb.N) were lower with age (r=-0.23, -0.35) (r=-0.36,-0.33), and trabecular separation (Tb.Sp) and the star volume of marrow space (V*ms) were higher with age (r=0.29, 0.41) (r=0.34, 0.38) in both the radius and tibia. In cortical bone, cortical volumetric BMD (Ct.vBMD) was lower with age (r=-0.25, -0.52), and cortical porosity (Ct.Po) was higher with age (r=0.67, 0.62) in both the radius and tibia. In the tibia, cortical thickness (Ct.Th) and cortical area (Ct.Ar) were lower with age (r=-0.40) (r=-0.43), whereas, in the radius, they were maintained, and periosteal perimeter (Ct.Pm) was higher with age (r=0.35). aBMD in the proximal femur and P1NP were lower, and pentosidine was higher with increased age, whereas aBMD in the lumbar spine, TRACP-5b, and 25(OH) vitamin D had no relationships with age. DXA and HR-pQCT showed strong correlations particularly with femoral aBMD and tibial Tb.vBMD and Ct.Ar (r=0.61) (r=0.61), whereas no DXA parameters were related with Ct.Po. In correlations between biochemical markers and HR-pQCT, TRACP-5b and total P1NP were negatively correlated with Ct.vBMD (r=-0.31) (r=-0.35), but almost no other correlations were seen. Age-related changes of the bone microstructure in men were characterized by decreases in trabecular and cortical vBMD associated with decreased trabecular number, cavitation of the trabecular structure, and increased cortical porosity. Femoral aBMD was strongly related to bone microstructure in the tibia, whereas both lumbar aBMD and femoral aBMD were not related to Ct.Po, and biochemical markers showed almost no relationships with bone microstructure.

Characterization of Age-Related Differences in the Human Choroid Plexus Volume, Microstructural Integrity, and Blood Perfusion Using Multiparameter Magnetic Resonance Imaging.

The choroid plexus (CP) is an important cerebral structure involved in cerebrospinal fluid production and transport of solutes into the brain. Recent studies have uncovered the involvement of the CP in neurological disorders such as Alzheimer’s disease and multiple sclerosis. However, our understanding of human age-related microstructural and functional changes in the CP with aging and neuropathology is limited. In this cross-sectional study, we investigated age and sex differences in the CP structure and function using advanced quantitative magnetic resonance imaging methodology in a large cohort (n = 155) of cognitively unimpaired individuals over a wide age range between 21 and 94 years. Our analysis included volumetric measurements, relaxometry measures (T1 and T2), diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) and mean diffusivity (MD), as well as measures of cerebral blood flow (CBF). Our results revealed that CP volume was increasing with advancing age. We conjecture that this novel observation is likely attributed to alterations in the CP microstructure or function as well as to ventriculomegaly. Indeed, we also found that CBF was lower with advanced age, while, consistent with previous studies, T1, T2 and MD were higher, and FA was lower with advanced age. We attribute these functional and microstructural differences to a deteriorated CP structural integrity with aging. Furthermore, our relaxometry and DTI measures were found to be associated with differences in blood perfusion revealing lower microstructural integrity with lower CBF. Finally, in agreement with literature, sex-related differences in MD and CBF were statistically significant. This work lays the foundation for ongoing investigation of the involvement of CP in neurodegeneration.

White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction

The macro- and microstructural architecture of human brain white matter undergoes substantial alterations throughout development and ageing. Most of our understanding of the spatial and temporal characteristics of these lifespan adaptations come from magnetic resonance imaging (MRI), including diffusion MRI (dMRI), which enables visualisation and quantification of brain white matter with unprecedented sensitivity and detail. However, with some notable exceptions, previous studies have relied on cross-sectional designs, limited age ranges, and diffusion tensor imaging (DTI) based on conventional single-shell dMRI. In this mixed cross-sectional and longitudinal study (mean interval: 15.2 months) including 702 multi-shell dMRI datasets, we combined complementary dMRI models to investigate age trajectories in healthy individuals aged 18 to 94 years (57.12% women). Using linear mixed effect models and machine learning based brain age prediction, we assessed the age-dependence of diffusion metrics, and compared the age prediction accuracy of six different diffusion models, including diffusion tensor (DTI) and kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), restriction spectrum imaging (RSI), spherical mean technique multi-compartment (SMT-mc), and white matter tract integrity (WMTI). The results showed that the age slopes for conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) were largely consistent with previous research, and that the highest performing advanced dMRI models showed comparable age prediction accuracy to conventional DTI. Linear mixed effects models and Wilk's theorem analysis showed that the ‘FA fine’ metric of the RSI model and ‘orientation dispersion’ (OD) metric of the NODDI model showed the highest sensitivity to age. The results indicate that advanced diffusion models (DKI, NODDI, RSI, SMT mc, WMTI) provide sensitive measures of age-related microstructural changes of white matter in the brain that complement and extend the contribution of conventional DTI.

Associations between age-related changes in bone microstructure and strength and dietary acid load in a cohort of community-dwelling, healthy men and postmenopausal women

The importance of dietary acid load (DAL) in the pathogenesis of osteoporosis is still debated. Age-related changes in bone microstructure and strength in relation to DAL remain largely unexplored. We investigated the associations between changes in areal and volumetric bone mineral density (BMD), bone microstructure and strength, fracture risk, and DAL in a prospective cohort of 65-y-old healthy men and postmenopausal women. Potential renal acid load (PRAL; mEq/d) was calculated as a DAL proxy to characterize participants' diet as alkaline (Alk-D; PRAL < -5), neutral (Neut-D; -5≤PRAL≤5), or acidic (Acid-D; PRAL >5). We measured areal BMD (aBMD) by DXA, and distal radius and tibia bone microstructure using high-resolution peripheral quantitative computed tomography, at baseline (n=853) and after 6.1±1.4 y (n=708). Bone strength was estimated using finite element analyses at baseline and after 3.0±0.5 y (n=613). Prevalent and incident fractures were recorded. The majority of the participants (59%) had an Alk-D, while 23% had a Neut-D, and 18% an Acid-D. Baseline aBMD and bone microstructure and strength did differ or were slightly better in women or men with an Acid-D versus those consuming an Alk-D or Neut-D. Indeed, women with an Acid-D had higher trabecular number (P=0.010 vs. Alk-D; P=0.001 vs. Neut-D), while men had higher hip and radius aBMD (P=0.008 and 0.024 vs. Neut-D, respectively) and radius strength (P=0.026 vs. Neut-D). Over the follow-up, women in the Acid-D group experienced lower cortical and endocortical bone loss at the radius than did the Alk-D and Neut-D groups (cortical thickness, P=0.008 and<0.001; trabecular area, P=0.001 and<0.001, respectively). No association between fractures and PRAL was observed. These null or favourable associations between baseline values or changes in aBMD, bone microstructure and strength, and DAL in this cohort of 65-y-old healthy individuals do not support adverse DAL-mediated effects on bone. This trial was registered at http://www.isrctn.com as ISRCTN11865958.

Intra- and interhemispheric white matter tract associations with auditory spatial processing: Distinct normative and aging effects

Declining auditory spatial processing is hypothesized to contribute to the difficulty older adults have detecting, locating, and selecting a talker from among others in noisy listening environments. Though auditory spatial processing has been associated with several cortical structures, little is known regarding the underlying white matter architecture or how age-related changes in white matter microstructure may affect it. The arcuate fasciculus is a target for understanding age-related differences in auditory spatial attention based on normative spatial attention findings in humans. Similarly, animal and human clinical studies suggest that the corpus callosum plays a role in the cross-hemispheric integration of auditory spatial information important for spatial localization and attention. The current investigation used diffusion imaging to examine the extent to which age-group differences in the identification of spatially cued speech were accounted for by individual differences in the white matter microstructure of the right arcuate fasciculus and the corpus callosum. Higher right arcuate and callosal fractional anisotropy (FA) predicted better segregation and identification of spatially cued speech across younger and older listeners. Further, individual differences in callosal microstructure mediated age-group differences in auditory spatial processing. Follow-up analyses suggested that callosal tracts connecting left and right pre-frontal and posterior parietal cortex are particularly important for auditory spatial processing. The results are consistent with previous work in animals and clinical human samples and provide a cortical mechanism to account for age-related deficits in auditory spatial processing. Further, the results suggest that both intrahemispheric and interhemispheric mechanisms are involved in auditory spatial processing.

Characterization of age-related microstructural changes in locus coeruleus and substantia nigra pars compacta

Locus coeruleus (LC) and substantia nigra pars compacta (SNpc) degrade with normal aging, but not much is known regarding how these changes manifest in MRI images, or whether these markers predict aspects of cognition. Here, we use high-resolution diffusion-weighted MRI to investigate microstructural and compositional changes in LC and SNpc in young and older adult cohorts, as well as their relationship with cognition. In LC, the older cohort exhibited a significant reduction in mean and radial diffusivity, but a significant increase in fractional anisotropy compared with the young cohort. We observed a significant correlation between the decrease in LC mean, axial, and radial diffusivities and measures examining cognition (Rey Auditory Verbal Learning Test delayed recall) in the older adult cohort. This observation suggests that LC is involved in retaining cognitive abilities. In addition, we observed that iron deposition in SNpc occurs early in life and continues during normal aging.

Lagged Coupled Changes Between White Matter Microstructure and Processing Speed in Healthy Aging: A Longitudinal Investigation

Age-related differences in white matter (WM) microstructure have been linked to lower performance in tasks of processing speed in healthy older individuals. However, only few studies have examined this link in a longitudinal setting. These investigations have been limited to the correlation of simultaneous changes in WM microstructure and processing speed. Still little is known about the nature of age-related changes in WM microstructure, i.e., regionally distinct vs. global changes. In the present study, we addressed these open questions by exploring whether previous changes in WM microstructure were related to subsequent changes in processing speed: (a) 1 year later; or (b) 2 years later. Furthermore, we investigated whether age-related changes in WM microstructure were regionally specific or global. We used data from four occasions (covering 4 years) of the Longitudinal Healthy Aging Brain (LHAB) database project (N = 232; age range at baseline = 64–86). As a measure of WM microstructure, we used mean fractional anisotropy (FA) in 10 major WM tracts averaged across hemispheres. Processing speed was measured with four cognitive tasks. Statistical analyses were conducted with bivariate latent change score (LCS) models. We found, for the first time, evidence for lagged couplings between preceding changes in FA and subsequent changes in processing speed 2 years, but not 1 year later in some of the WM tracts (anterior thalamic radiation, superior longitudinal fasciculus). Our results supported the notion that FA changes were different between regional WM tracts rather than globally shared, with some tracts showing mean declines in FA, and others remaining relatively stable across 4 years.

Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation

Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline.In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20–77 years) using 3.0T and 12 b-values up to 5000 s/mm2. Association between diffusion metrics and subjects’ age was assessed using linear regression. A decline in mean γ (Mγ) in the scGM and a complementary increase in radial γ (γ⊥) in frontal WM, genu of corpus callosum and anterior corona radiata with advancing age were found. We suggested that the increase in γ⊥ might reflect declined myelin density, and Mγ decrease might mirror iron accumulation. An increase in D// and a decrease in the orientation dispersion index (ODI) were associated with axonal loss in the pyramidal tracts, while their inverted trends within the thalamus were thought to be linked to reduced architectural complexity of nerve fibers. γ-metrics together with conventional diffusion-metrics can more comprehensively characterize the complex mechanisms underlining age-related changes than conventional diffusion techniques alone.

Maturation-Related Changes in T2 Relaxation Times of Cartilage and Meniscus of the Pediatric Knee Joint at 3 T.

The objective of our study was to use a T2 mapping sequence performed at 3 T to investigate changes in the composition and microstructure of the cartilage and menisci of the pediatric knee joint during maturation. This retrospective study was performed of MRI examinations of 76 pediatric knees without internal derangement in 72 subjects (29 boys [mean age, 12.5 years] and 43 girls [mean age, 13.0 years]) who were evaluated with a sagittal T2 mapping sequence. T2 relaxation time values were quantitatively measured in eight cartilage subregions and in the medial and lateral menisci. Wilcoxon rank sum and Kruskal-Wallis tests were used to analyze the relationship between cartilage and meniscus T2 relaxation time values and sex and skeletal maturation, respectively. A multivariate linear regression model was used to investigate the independent association between cartilage T2 relaxation time values and age, weight, and body mass index (BMI [weight in kilograms divided by the square of height in meters]). There were no significant sex differences (p = 0.26-0.91) in T2 relaxation time values for cartilage or meniscus. T2 relaxation time values in each individual cartilage subregion significantly decreased (p < 0.001) with progressive maturation. T2 relaxation time values in the lateral meniscus significantly increased (p = 0.001) with maturation, whereas T2 relaxation time values in the medial meniscus did not significantly change (p = 0.82). There was a significant association (p < 0.001) between cartilage T2 relaxation time values and age independent of weight and BMI, but no significant association between cartilage T2 relaxation time values and weight (p = 0.06) and BMI (p = 0.20) independent of age. Cartilage T2 relaxation time values significantly decreased in all cartilage subregions and meniscus T2 relaxation time values significantly increased in the lateral meniscus during maturation. These changes in T2 relaxation time values reflect age-related changes in tissue composition and microstructure.

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals (n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa.

Whole brain analyses of age-related microstructural changes quantified using different diffusional magnetic resonance imaging methods.

The new diffusional magnetic resonance imaging (dMRI) techniques, diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) have been developed to clarify the microstructural changes. To our knowledge, however, there is little information on the similarities and differences of these metrics evaluated by the image-by-image paired t test. Twenty-three healthy subjects underwent dMRI. We estimated the relationships of these metrics evaluated by the image-by-image paired t-test and compared aging effects on each metric. We found that fractional anisotropy (FA), mean kurtosis (MK) derived from DKI and neurite density index (NDI) values derived from NODDI correlated with each other positively, and mean diffusivity (MD) and orientation dispersion index (ODI) values from NODDI correlated negatively with the FA value. There were no significant relationships of age with FA or MD values, while MK, ODI and NDI values showed significant correlations with age. These results may indicate not only the similar tendency among the metrics, but also the higher sensitivity of NODDI and DKI to the changes in microstructural tissue organization with advancing age. These techniques could shed light on both normal and degenerated brain changes.

Diffusion Kurtosis Imaging of Microstructural Alterations in the Brains of Paediatric Patients with Congenital Sensorineural Hearing Loss

Our aim was to assess microstructural alterations in the cerebrums of paediatric patients with congenital sensorineural hearing loss (SNHL) using diffusion kurtosis imaging (DKI). Seventy-two paediatric SNHL patients and 38 age-matched healthy volunteers were examined via DKI using a 3.0 T magnetic resonance (MR) imager. Fractional anisotropy (FA) and mean kurtosis (MK) values were computed for 12 cerebral regions in both the controls and the SNHL patients. Compared with patients below age 3, patients in the older age group were found to have more significant differences in MK than in FA, and these appeared in more major areas of the brain. In contrast, in 1- to 3-year-old children, a few major brain areas exhibited differences in FA, but none exhibited appreciable differences in MK. There were significant decreases in the FA or MK values (P < 0.05, all) in more areas of the brain in patients with lesions than in patients with normal-appearing brains. DKI offers comprehensive measurements for quantitative evaluation of age-related microstructural changes in both white and grey matter in SNHL patients. DKI scans of children with SNHL exhibiting significant decreases in MK might play an important role in evaluating the severity of developmental delay.

Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder

Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging. Cross-sectional study. University of California San Diego and the Veterans Administration San Diego Healthcare System. 33 euthymic BD and 38 HC participants. Diffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test. BD participants demonstrated slower PS compared with the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum, and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently. Results provide support for future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.