Age-related Cortical Thinning Research Articles

Disturbances in primary visual processing as a function of healthy aging

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer's disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age.

Brain network architecture constrains age-related cortical thinning

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including “hotspots” of pronounced age effects in sensorimotor areas. Regional age-related differences were strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Association of Cannabis Use and Neurodevelopment Among Adolescents

Source: Albaugh MD, Ottino-Gonzalez J, Sidwell A, et al Association of cannabis use during adolescence with neurodevelopment [published online ahead of print June 16, 2021]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2021.1258Investigators from multiple institutions reviewed data from a longitudinal study to assess the association between cannabis use during adolescence and cerebral cortical thickness development as measured using MRI. Participants were enrolled in the IMAGEN study, conducted across 8 European sites, when they were approximately 14 years old. Using a standard protocol, MRI scans were obtained of the adolescents’ brains at enrollment and a 5-year follow-up visit. In addition, at baseline and at follow-up, study participants completed the European School Survey Project on Alcohol and Other Drugs (ESPAD), in which lifetime use of alcohol, nicotine, and cannabis is self-reported using a 7-point scale with usage ranging from “never” to “>40 times.” Only youths who reported never using cannabis at baseline and had baseline and 5-year data were included in the present study. At the 5-year follow-up, participants also completed the Barratt Impulsiveness Scale, a 30-item self-report that assesses 3 domains of impulsiveness (attentional, non-planning, and motor). Alcohol consumption was estimated at baseline and 5-year follow-up with the Alcohol Use Disorders Identification Test Consumption scale.Cross-sectional regression models were used to assess the association between lifetime cannabis use and local cortical thickness. Longitudinal models were used to identify areas of accelerated age-related cortical thinning associated with cannabis use and to evaluate the association between the 3 domains of impulsiveness as measured by the Barratt Impulsiveness Scale.A total of 799 youths who were cannabis-naïve at baseline were included in the analyses. Mean age of these participants at baseline was 14.0 ±0.4 years, and 56.3% were female. At the 5-year follow-up, 208 participants (26.0%) reported 1-9 lifetime uses of cannabis, and 161 (20.2%) reported 10 to >40 uses. On cross-sectional analysis, there was a dose-dependent, statistically significant negative association between cortical thickness in the left prefrontal and right prefrontal cortices and lifetime cannabis use assessed at the 5-year follow-up. No statistically significant relationships were found between lifetime cannabis use and cortical thickness on baseline MRI results, suggesting that differences observed at follow-up did not precede cannabis use. On longitudinal analysis, statistically significant associations between accelerated age-related thinning in both the left and right prefrontal cortices were found. There was no significant difference in the effects of cannabis on cortical thickness between females and males in either the cross-sectional or longitudinal analyses. Cannabis-related cortical thinning in the right dorsomedial prefrontal cortex was significantly associated with more attentional impulsiveness as measured by the Barratt Impulsiveness Scale.The authors conclude that cannabis use during adolescence was associated with altered neurodevelopment.Dr Doolittle has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Cannabis use has become more popular and socially accepted in recent years. Many states have decriminalized marijuana use and expanded licensing for dispensaries.1 Nearly 50% of adolescents consider marijuana to be easily accessible, and 28% believe it to have no or low health risks.1 Nearly 1 in 10 persons older than 12 years of age has used marijuana within the past month.2 Large studies of marijuana derivatives, such as tetrahydrocannabinol and cannabidiol, have demonstrated improvement in a range of medical conditions, such as chemotherapy-related nausea, spasticity in multiple sclerosis, and chronic pain.3,4 As marijuana becomes more widely accepted, however, its deleterious effects are often overlooked. This is especially important among adolescents, whose cerebral cortex has not yet fully matured.5 In fact, the current authors describe thinning of the cerebral cortex of adolescent brains based on the cumulative dose of marijuana ingested. In addition, these anatomic effects are associated with a measurable behavioral change: attentional impulsiveness.While the decriminalization of marijuana has resulted in important legal reform, marijuana is best regarded as a drug, akin to alcohol. Use by adolescents ought to be discouraged, except when its medical benefit exceeds its potential harmful effect. While the investigators in the current study do not address the impact of marijuana beyond the 5-year follow-up, other large population studies highlight the association of marijuana use and harmful outcomes, such as respiratory problems, increased depression and anxiety, impaired executive function, poor school performance, and poverty.6,7The current study is the largest longitudinal study of its kind, making an important contribution to ongoing debate of marijuana’s harm and efficacy. Despite marijuana’s increasing popularity, pediatric caregivers should continue to advise caution.Marijuana use among adolescents is associated with cortical thinning and increased impulsiveness.

How Do We Motorically Resonate in Aging? A Compensatory Role of Prefrontal Cortex.

Aging is the major risk factor for chronic age-related neurological diseases such as neurodegenerative disorders and neurovascular injuries. Exploiting the multimodal nature of the Mirror Neuron System (MNS), rehabilitative interventions have been proposed based on motor-resonance mechanisms in recent years. Despite the considerable evidence of the MNS’ functionality in young adults, further investigation of the action-observation matching system is required in aging, where well-known structural and functional brain changes occur. Twenty-one healthy young adults (mean age 26.66y) and 19 healthy elderly participants (mean age 71.47y) underwent a single MRI evaluation including a T1-3D high-resolution and functional MRI (fMRI) with mirror task. Morphological and functional BOLD data were derived from MRI images to highlight cortical activations associated with the task; to detect differences between the two groups (Young, Elderly) in the two MRI indexes (BOLD and thickness z-scores) using mixed factorial ANOVA (Group∗Index analyses); and to investigate the presence of different cortical lateralization of the BOLD signal in the two groups. In the entire sample, the activation of a bilateral MNS fronto-parietal network was highlighted. The mixed ANOVA (pFDR-corr < 0.05) revealed significant interactions between BOLD signal and cortical thickness in left dorsal premotor cortex, right ventral premotor and prefrontal cortices. A different cortical lateralization of the BOLD signal in frontal lobe activity between groups was also found. Data herein reported suggest that age-related cortical thinning of the MNS is coupled with increased interhemispheric symmetry along with premotor and prefrontal cortex recruitment. These physiological changes of MNS resemble the aging of the motor and cognitive neural systems, suggesting specific but also common aging and compensatory mechanisms.

Association of Cannabis Use During Adolescence With Neurodevelopment

Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans. To examine the degree to which magnetic resonance (MR) imaging-assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents. Data were obtained from the community-based IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants were identified who reported being cannabis naive at study baseline and had behavioral and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was performed from October 1, 2019, to August 31, 2020. Cannabis use was assessed at baseline and 5-year follow-up with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo sequence. Quality-controlled native MR images were processed through the CIVET pipeline, version 2.1.0. The study evaluated 1598 MR images from 799 participants (450 female participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated with thickness in left prefrontal (peak: t785 = -4.87, cluster size = 1558 vertices; P = 1.10 × 10-6, random field theory cluster corrected) and right prefrontal (peak: t785 = -4.27, cluster size = 1551 vertices; P = 2.81 × 10-5, random field theory cluster corrected) cortices. There were no significant associations between lifetime cannabis use at 5-year follow-up and baseline cortical thickness, suggesting that the observed neuroanatomical differences did not precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical thinning was qualified by cannabis use in a dose-dependent fashion such that greater use, from baseline to follow-up, was associated with increased thinning in left prefrontal (peak: t815.27 = -4.24, cluster size = 3643 vertices; P = 2.28 × 10-8, random field theory cluster corrected) and right prefrontal (peak: t813.30 = -4.71, cluster size = 2675 vertices; P = 3.72 × 10-8, random field theory cluster corrected) cortices. The spatial pattern of cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540; P < .001), and a positron emission tomography-assessed cannabinoid 1 receptor-binding map derived from a separate sample of participants (r = -0.189; P < .001). Analysis revealed that thinning in right prefrontal cortices, from baseline to follow-up, was associated with attentional impulsiveness at follow-up. Results suggest that cannabis use during adolescence is associated with altered neurodevelopment, particularly in cortices rich in cannabinoid 1 receptors and undergoing the greatest age-related thickness change in middle to late adolescence.

Development of attention networks from childhood to young adulthood: A study of performance, intraindividual variability and cortical thickness

Human cognitive development is manifold, with different functions developing at different speeds at different ages. Attention is an important domain of this cognitive development, and involves distinct developmental trajectories for separate functions, including conflict processing, selection of sensory input and alertness. In children, several studies using the Attention Network Test (ANT) have investigated the development of three attentional networks that carry out the functions of executive control, orienting and alerting. There is, however, a lack of studies on the development of these attentional components across adolescence, limiting our understanding of their protracted development. To fill this knowledge gap, we performed a mixed cross-sectional and longitudinal study using mixed methods to examine the development of the attentional components and their intraindividual variability from late childhood to young adulthood (n = 287, n observations = 408, age range = 8.5–26.7 years, mean follow up interval = 4.4 years). The results indicated that executive control stabilized during late adolescence, while orienting and alerting continued to develop into young adulthood. In addition, a continuous development into young adulthood was observed for the intraindividual variability measures of orienting and alerting. In a subsample with available magnetic resonance imaging (MRI) data (n = 169, n observations = 281), higher alerting scores were associated with thicker cortices within a right prefrontal cortical region and greater age-related cortical thinning in left rolandic operculum, while higher orienting scores were associated with greater age-related cortical thinning in frontal and parietal regions. Finally, increased consistency of orienting performance was associated with thinner cortex in prefrontal regions and reduced age-related thinning in frontal regions.

Disease-related cortical thinning in presymptomatic granulin mutation carriers

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

The Effect of a Multicomponent Dual-Task Exercise on Cortical Thickness in Older Adults with Cognitive Decline: A Randomized Controlled Trial.

The aim of this study was to examine cortical thickness changes associated with a multicomponent exercise intervention combining physical exercise and cognitive training in older adults with cognitive decline. This study involved a secondary analysis of neuroimaging data from a randomized controlled trial with 280 older adults having cognitive decline who were randomly assigned to either a multicomponent exercise group (n = 140) that attended weekly 90-minute exercise and cognitive training sessions or a health education control group (n = 140). The cortical thickness and cognitive performance were assessed at the baseline and at trial completion (10 months). The cortical thickness in the frontal and temporal regions was determined using FreeSurfer software. Cognitive performance was evaluated using the Gerontology-Functional Assessment Tool (NCGG-FAT). The cortical thickness significantly increased in the middle temporal (p < 0.001) and temporal pole (p < 0.001) in the multicomponent exercise group compared with the control group. Cortical thickness changes were significantly associated with change in trail making test (TMT)-A, TMT-B, and story memory after a 10-month multicomponent exercise intervention. This study suggests that multicomponent exercise programs combining physical exercise and cognitive training have important implications for brain health, especially in providing protection from age-related cortical thinning.

Aging and central vision loss: Relationship between the cortical macro-structure and micro-structure

Aging and central vision loss are associated with cortical atrophies, but little is known about the relationship between cortical thinning and the underlying cellular structure. We compared the macro- and micro-structure of the cortical gray and superficial white matter of 38 patients with juvenile (JMD) or age-related (AMD) macular degeneration and 38 healthy humans (19–84 years) by multimodal MRI including diffusion-tensor imaging (DTI). A factor analysis showed that cortical thickness, tissue-dependent measures, and DTI-based measures were sensitive to distinct components of brain structure. Age-related cortical thinning and increased diffusion were observed across most of the cortex, but increased T1-weighted intensities (frontal), reduced T2-weighted intensities (occipital), and reduced anisotropy (medial) were limited to confined cortical regions. Vision loss was associated with cortical thinning and enhanced diffusion in the gray matter (less in the white matter) of the occipital central visual field representation. Moreover, AMD (but not JMD) patients showed enhanced diffusion in lateral occipito-temporal cortex and cortical thinning in the posterior cingulum. These findings demonstrate that changes in brain structure are best quantified by multimodal imaging. They further suggest that age-related brain atrophies (cortical thinning) reflect diverse micro-structural etiologies. Moreover, juvenile and age-related macular degeneration are associated with distinct patterns of micro-structural alterations.

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open‐access healthy cohort (n = 102, age range = 30–89 years) with MRI and Aβ PET data, we estimated age‐related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface‐based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting‐state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory‐motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long‐axis. While age‐related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced toward higher‐order transmodal regions. Age‐related atrophy was greater toward the posterior end of the hippocampal long‐axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography‐specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain‐based biomarkers of aging.

Distinct Brain Regions in Physiological and Pathological Brain Aging.

BackgroundStudying structural brain aging is important to understand age-related pathologies, as well as to identify the early manifestations of the Alzheimer’s disease (AD) continuum. In this study, we investigated the long-term trajectory of physiological and pathological brain aging in a large number of participants ranging from the 50s to over 80 years of age.ObjectiveTo explore the distinct brain regions that distinguish pathological brain aging from physiological brain aging using sophisticated measurements of cortical thickness.MethodsA total of 2,823 cognitively normal (CN) individuals and 2,675 patients with AD continuum [874 with subjective memory impairment (SMI), 954 with amnestic mild cognitive impairment (aMCI), and 847 with AD dementia] who underwent a high-resolution 3.0-tesla MRI were included in this study. To investigate pathological brain aging, we further classified patients with aMCI and AD according to the severity of cognitive impairment. Cortical thickness was measured using a surface-based method. Multiple linear regression analyses were performed to evaluate age, diagnostic groups, and cortical thickness.ResultsAging extensively affected cortical thickness not only in CN individuals but also in AD continuum patients; however, the precuneus and inferior temporal regions were relatively preserved against age-related cortical thinning. Compared to CN individuals, AD continuum patients including those with SMI showed a decreased cortical thickness in the perisylvian region. However, widespread cortical thinning including the precuneus and inferior temporal regions were found from the late-stage aMCI to the moderate to severe AD. Unlike the other age groups, AD continuum patients aged over 80 years showed prominent cortical thinning in the medial temporal region with relative sparing of the precuneus.ConclusionOur findings suggested that the precuneus and inferior temporal regions are the key regions in distinguishing between physiological and pathological brain aging. Attempts to differentiate age-related pathology from physiological brain aging at a very early stage would be important in terms of establishing new strategies for preventing accelerated pathological brain aging.

Thinning faster? Age-related cortical thickness differences in adults with autism spectrum disorder

BackgroundOver the course of the last 30 years, autism spectrum disorder (ASD) diagnoses have increased, thus identifying a large group of aging individuals with ASD. Currently, little is known regarding how aging will affect these individual's neuroanatomy, compared to the neurotypical (NT) population. Because of the anatomical overlap of ASD-related cortical pathology and age-related cortical thinning, both following an anterior-to-posterior severity gradient, we hypothesize adults with ASD will show larger age-related cortical thinning than NT adults. MethodsWe analyzed cortical measurements using available data from the multi-site Autism Brain Imaging Data Exchange I (ABIDE I; n = 282) and our own cohort of middle-age to older adults with and without ASD (n = 47) mostly available in ABIDE II (n = 35). We compared correlations between cortical measures and age in right-handed adults with ASD (n = 157) and similar NT adults (n = 172), controlling for IQ and site. Participants were 18–64 years of age (mean = 29.8 years; median = 26 years). ResultsWe found significant differences between diagnosis groups in the relationship between age and cortical thickness for areas of left frontal lobe (pars opercularis), temporal lobe (inferior gyrus, middle gyrus, banks of the superior temporal sulcus, and entorhinal cortex), parietal lobe (inferior gyrus), and lateral occipital lobe. For all areas, adults with ASD showed a greater negative correlation between age and cortical thickness than NT adults. ConclusionAs hypothesized, adults with ASD demonstrated exacerbated age-related cortical thinning, compared to NT adults. These differences were the largest and most extensive in the left temporal lobe. Future longitudinal work is warranted to investigate whether differences in brain age trajectories will translate to unique behavioral needs in older adults with ASD.

Androgen Receptor in Neurons Slows Age-Related Cortical Thinning in Male Mice.

Androgens via the androgen receptor (AR) are required for optimal male bone health. The target cell(s) for the effects of androgens on cortical bone remain(s) incompletely understood. In females, estrogen receptor alpha in neurons is a negative regulator of cortical and trabecular bone. Whether neuronal AR regulates bone mass in males remains unexplored. Here, we inactivated AR in neurons using a tamoxifen-inducible CreERT2 under the control of the neuronal promoter Thy1. Tamoxifen induced a 70% to 80% reduction of AR mRNA levels in Thy1-CreERT2-positive brain regions cerebral cortex and brainstem as well as in the peripheral nervous tissue of male neuronal AR knockout (N-ARKO) mice. Hypothalamic AR mRNA levels were only marginally reduced and the hypothalamic-pituitary-gonadal axis remained unaffected, as determined by normal levels of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). In contrast to orchidectomy, deletion of neuronal AR did not alter body weight, body composition, hindlimb muscle mass, grip strength, or wheel running. MicroCT analysis of the femur revealed no changes in bone accrual during growth in N-ARKO mice. However, 36- and 46-week-old N-ARKO mice displayed an accelerated age-related cortical involution, namely a more pronounced loss of cortical thickness and strength, which occurred in the setting of androgen sufficiency. Neuronal AR inactivation decreased the cancellous bone volume fraction in L5 vertebra but not in the appendicular skeleton of aging mice. MicroCT findings were corroborated in the tibia and after normalization of hormonal levels. Serum markers of bone turnover and histomorphometry parameters were comparable between genotypes, except for a 30% increase in osteoclast surface in the trabecular compartment of 36-week-old N-ARKO mice. Cortical bone loss in N-ARKO mice was associated with an upregulation of Ucp1 expression in brown adipose tissue, a widely used readout for sympathetic tone. We conclude that androgens preserve cortical integrity in aging male mice via AR in neurons. © 2018 American Society for Bone and Mineral Research.

Accelerated age-related cortical thinning in mild traumatic brain injury.

IntroductionMild traumatic brain injury (mTBI) can result in many structural abnormalities in the cerebral cortex. While thinning of the cortex has been shown in mTBI patients, there is high regional variability in reported findings. High‐resolution imaging can elucidate otherwise unnoticed changes in cortical measures following injury. This study examined age‐related patterns of cortical thickness in U.S. active duty service members and veterans with a history of mTBI (n = 66) as compared to a normative population (n = 67).MethodsUsing a fully automated cortical parcellation methodology, cortical thickness measures were extracted from 31 bilateral cortical regions for all participants.ResultsThe effect of diagnosis and age on cortical thickness (group × age interaction) was found to be significant (p < 0.05) for many regions, including bilateral parietal and left frontal and temporal cortices. Findings held for a male‐only subset, and there was no effect of time since injury in any regions.ConclusionsThe presence of mTBI appeared to accelerate age‐related cortical thinning across the cortex in our study population.

Trajectories of Physiological Brain Aging and Related Factors in People Aged from 20 to over-80.

In this study, we investigated a long-term trajectory of brain aging (from the 20 s to over-80) in cognitively normal (CN) individuals. We further determined whether differences in sex, education years, and apolipoprotein E ε 4 status affect age-related cortical thinning. A total of 2,944 CN individuals who underwent high-resolution (3.0-Tesla) magnetic resonance imaging were included in this study. Cortical thickness was measured using a surface-based method. Multiple linear regression analyses were performed to evaluate age-related cortical thinning and related factors. Compared to those in their 20 s/30 s, participants in their 40 s showed thinning primarily in the medial and lateral frontal and inferior parietal regions, and cortical thinning occurred across most of the cortices with increasing age. Notably, the precuneus, inferior temporal and lateral occipital regions were relatively spared until later in life. Male and lower education years were associated with greater cortical thinning with distinct regional specificity. Our findings provide an important clue to understanding the mechanism of age-related cognitive decline and new strategies for preventing the acceleration of pathological brain aging.

Social Responsiveness Scale (SRS) in Relation to Longitudinal Cortical Thickness Changes in Autism Spectrum Disorder.

The relationship between brain development and clinical heterogeneity in autism (ASD) is unknown. This study examines the Social Responsiveness Scale (SRS) in relation to the longitudinal development of cortical thickness. Participants (N = 91 ASD, N = 56 TDC; 3-39years at first scan) were scanned up to three times over a 7-year period. Mixed-effects models examined cortical thickness in relation to SRS score. ASD participants with higher SRS scores showed regionally increased age-related cortical thinning. Regional thickness differences and reduced age-related cortical thinning were found in predominantly right lateralized regions in ASD with decreasing SRS scores over time. Our findings emphasize the importance of examining clinical phenotypes in brain-based studies of ASD.

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume.

ObjectiveThis study examined the effects of HIV infection, methamphetamine dependence and their interaction on cortical thickness, area and volume, as well as the potential interactive effects on cortical morphometry of HIV and methamphetamine with age.MethodT1-weighted structural images were obtained on a 3.0T General Electric MR750 scanner. Freesurfer v5.3.0 was used to derive cortical thickness, area and volume measures in thirty-four regions based on Desikan-Killiany atlas labels.ResultsFollowing correction for multiple statistical tests, HIV diagnosis was not significantly related to cortical thickness or area in any ROI, although smaller global cortical area and volume were seen in those with lower nadir CD4 count. HIV diagnosis, nevertheless, was associated with smaller mean cortical volumes in rostral middle frontal gyrus and in the inferior and superior parietal lobes. Methamphetamine dependence was significantly associated with thinner cortex especially in posterior cingulate gyrus, but was not associated with cortical area or volume following correction for multiple statistical tests. We found little evidence that methamphetamine dependence moderated differences in cortical area, volume or thickness for any ROI in the HIV seropositive group. Interactions with age revealed that HIV diagnosis attenuated the degree of age-related cortical thinning seen in non-infected individuals; intercepts indicated that young HIV seropositive individuals had thinner cortex than non-infected peers.ConclusionsMethamphetamine dependence does not appear to potentiate a reduction of cortical area, volume or thickness in HIV seropositive individuals. The finding of thinner cortex in young HIV seropositive individuals and the association between CD4 nadir and global cortical area and volume argue for prioritizing early antiretroviral treatment.

Psychiatric polygenic risk associates with cortical morphology and functional organization in aging

Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross. Interestingly, the genes in PRScross, that contributed most to aging neurodegeneration, were expressed in the functioanlly connected cortical regions. Especially, genes identified through the genotype-functional connectivity association analysis were commonly expressed in both cortical regions and formed strong gene networks with biological processes related to neural plasticity and synaptogenesis, regulated by glutamatergic and GABAergic transmission, neurotrophin signaling, and metabolism. This study suggested integrating genotype and transcriptome with neuroimage data sheds new light on the mechanisms of aging brain.

Precuneus abnormalities in middle-aged to older adults with depressive symptoms: An analysis of BDI-II symptom dimensions

We recently reported age-related increases in left precuneus cortical thickness (CT) in older adults with elevated total depressive symptoms. However, it is unclear whether abnormalities in precuneus surface area (SA) are also evident and whether specific symptom dimensions of depression moderated age effects on these measurements. Seventy-three adults completed the Beck Depression Inventory – 2nd edition (BDI-II) and underwent structural neuroimaging. Measures of CT and SA were extracted from the right and left precuneus via FreeSurfer. Regression models included regions of interest as dependent variables, with age, BDI-II subscale scores (e.g., affective, cognitive, and somatic symptoms), and their interactions as independent variables, controlling for mean hemispheric thickness (for CT) or total intracranial volume (for SA). A significant age × somatic symptom interaction was found for left precuneus CT, such that elevated levels of somatic symptoms were significantly associated with age-related cortical thinning. No depressive symptom dimensions moderated the relationship between age and SA, suggesting that CT may be a more sensitive measure of brain abnormalities in middle-aged to older adults with depressive symptoms.