Structure Of Brain Regions Research Articles

Abnormal Topological Organization of Human Brain Connectome in Primary Dysmenorrhea Patients Using Graph Theoretical Analysis.

Accumulating studies have revealed altered brain function and structure in regions linked to sensory, pain and emotion in individuals with primary dysmenorrhea (PD). However, the changes in the topological properties of the brain's functional connectome in patients with PD experiencing chronic pain remain poorly understood. Our study aimed to explore the mechanism of functional brain network impairment in individuals withPD through a graph-theoretic analysis. This study was a randomized controlled trial that included individuals with PD and healthy controls (HC) from June 2021 to June 2022. The experiment took place in the magnetic resonance imaging facility at Jiangxi Provincial People's Hospital. Static MRI scans were conducted on 23 female patients with PD and 23 healthy female controls. A two-sample t-test was conducted to compare the global and nodal indices between the two groups, while the Network-Based Statistics (NBS) method was utilized to explore the functional connectivity alterations between the groups. In the global index, The PD group exhibited decreased Sigma (p = 0.0432) and Gamma (p = 0.0470) compared to the HC group among the small-world network properties.(p<0.05) In the nodal index, the PD group displayed reduced betweenness centrality and increased degree centrality in the default mode network (DMN), along with decreased nodal efficiency and increased degree centrality in the visual network (VN). (P < 0.05, Bonferroni-corrected) Furthermore, in the connection analysis, PD patients showed altered functional connectivity in the basal ganglia network (BGN), VN, and DMN.(NBS corrected). Our results indicate that individuals with PD showed abnormal brain network efficiency and abnormal connection within DMN, VN and BGN related to pain matrix. These findings have important references for understanding the neural mechanism of pain in PD.

Neuroanatomical Signature of the Transition from Normal Cognition to MCI in Parkinson's Disease.

The progression of Parkinson's disease (PD) is often accompanied by cognitive decline. We had previously developed a brain age estimation program utilizing structural MRI data of 949 healthy individuals from publicly available sources. Structural MRI data of 244 PD patients who were cognitively normal at baseline was acquired from the Parkinson Progression Markers Initiative (PPMI). 192 of these showed stable normal cognitive function from baseline out to 5 years (PD-SNC), and the remaining 52 had unstable normal cognition and developed mild cognitive impairment within 5 years (PD-UNC). 105 healthy controls were also included in the analysis as a reference. First, we examined if there were any baseline differences in regional brain structure between PD-UNC and PD-SNC cohorts utilizing the three most widely used atrophy estimation pipelines, i.e., voxel-based morphometry (VBM), deformation-based morphometry and cortical thickness analyses. We then investigated if accelerated brain age estimation with our multivariate regressive machine learning algorithm was different across these groups (HC, PD-SNC, and PD-UNC). As per the VBM analysis, PD-UNC patients demonstrated a noticeable increase in GM volume in the posterior and anterior lobes of the cerebellum, sub-lobar, extra-nuclear, thalamus, and pulvinar regions when compared to PD-SNC at baseline. PD-UNC patients were observed to have significantly older brain age compared to both PD-SNC patients (p=0.009) and healthy controls (p<0.009). The increase in GM volume in the PD-UNC group could potentially indicate an inflammatory or neuronal hypertrophy response, which could serve as a biomarker for future cognitive decline among this population.

Association of in utero HIV exposure with child brain structure and language development: a South African birth cohort study

BackgroundThere is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment.MethodsThe Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother–child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2–3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed.ResultsAnalyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size − 0.44 [95% CI − 0.78 to − 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032).ConclusionsIn this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

Associations of brain morphology with cortical proteins of cognitive resilience

In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline.

Adverse childhood experiences differently affect Theory of Mind brain networks in schizophrenia and healthy controls

Patients with schizophrenia (SZ) show impairments in both affective and cognitive dimensions of theory of mind (ToM). SZ are also particularly vulnerable to detrimental effect of adverse childhood experiences (ACE), influencing the overall course of the disorder and fostering poor social functioning. ACE associate with long-lasting detrimental effects on brain structure, function, and connectivity in regions involved in ToM. Here, we investigated whether ToM networks are differentially affected by ACEs in healthy controls (HC) and SZ, and if these effects can predict the disorder clinical outcome. 26 HC and 33 SZ performed a ToM task during an fMRI session. Whole-brain functional response and connectivity (FC) were extracted, investigating the interaction between ACEs and diagnosis. FC values significantly affected by ACEs were entered in a cross-validated LASSO regression predicting Positive and Negative Syndrome Scale (PANSS), Interpersonal Reactivity Index (IRI), and task performance. ACEs and diagnosis showed a widespread interaction at both affective and cognitive tasks, including connectivity between vmPFC, ACC, precentral and postcentral gyri, insula, PCC, precuneus, parahippocampal gyrus, temporal pole, thalamus, and cerebellum, and functional response in the ACC, thalamus, parahippocampal gyrus and putamen. FC predicted the PANSS score, the fantasy dimension of IRI, and the AToM response latency. Our results highlight the crucial role of early stress in differentially shaping ToM related brain networks in HC and SZ. These effects can also partially explain the clinical and behavioral outcomes of the disorder, extending our knowledge of the effects of ACEs.

Associations of cerebrospinal fluid complement proteins with Alzheimer’s pathology, cognition, and brain structure in non-dementia elderly

BackgroundCerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer’s disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated.MethodsA total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes.ResultsWe found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05).ConclusionsThis study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.

Causal associations between gut microbiota and regional cortical structure: a Mendelian randomization study.

Observational studies have reported associations between gut microbiota composition and central nervous system diseases. However, the potential causal relationships and underlying mechanisms remain unclear. Here, we applied Mendelian randomization (MR) to investigate the causal effects of gut microbiota on cortical surface area (SA) and thickness (TH) in the brain. We used genome-wide association study summary statistics of gut microbiota abundance in 18,340 individuals from the MiBioGen Consortium to identify genetic instruments for 196 gut microbial taxa. We then analyzed data from 56,761 individuals from the ENIGMA Consortium to examine associations of genetically predicted gut microbiota with alterations in cortical SA and TH globally and across 34 functional brain regions. Inverse-variance weighted analysis was used as the primary MR method, with MR Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out analysis to assess heterogeneity and pleiotropy. At the functional region level, genetically predicted higher abundance of class Mollicutes was associated with greater SA of the medial orbitofrontal cortex (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002), as was higher abundance of phylum Tenericutes (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002). Additionally, higher abundance of phylum Tenericutes was associated with greater SA of the lateral orbitofrontal cortex (β = 10.51 mm2, 95% CI: 3.24-17.79 mm2, p = 0.0046). No evidence of heterogeneity or pleiotropy was detected. Specific gut microbiota may causally influence cortical structure in brain regions involved in neuropsychiatric disorders. The findings provide evidence for a gut-brain axis influencing cortical development, particularly in the orbitofrontal cortex during adolescence.

Regional Brain Structure Mediates Age‐Related Decline in Eye Movement Control

AbstractBackgroundEye movements (EM) are considered potential biomarkers of neurodegeneration because they are altered in patients with neurodegenerative disease, including Alzheimer’s disease (AD). Alterations in EM control have also been observed in old age, with particularly strong age effects on saccadic latency, inhibitory errors in the antisaccade task, and smooth pursuit accuracy. The goal of our study was to characterize the neural pathways of age‐related changes in these EM outcomes.MethodThe analysis was based on 8,318 participants (aged 30 to 95 years) from the population‐based Rhineland Study. EMs were recorded using video‐based infrared oculography at 1,000 Hz. Volumes and thickness measures of selected brain structures were obtained using FreeSurfer from 3 Tesla T1‐weighted MR images. Relations of brain structure with EM outcomes were quantified using multivariable linear regression models. Brain structure variables were also analyzed as potential mediators in the relation between age and EM outcomes using causal mediation analysis under a counterfactual framework.ResultIn women, higher volume of the right thalamus and right globus pallidus was associated with lower antisaccade latency, whereas higher cortical thickness in the anterior cingulate cortex was associated with higher antisaccade latency. Higher cortical thickness in right supramarginal gyrus and right paracentral lobule and sulcus was associated with fewer antisaccade errors in women. There were no significant associations between regional brain structure and antisaccade performance in men. Higher cortical thickness in the right calcarine sulcus was associated with higher smooth pursuit velocity gain in both men and women. Additionally, individual brain structures mediated up to 11% of the age‐related decline in EM performance.ConclusionOur results support that EMs indeed reflect neurodegenerative processes as changes in brain structure partly account for age‐related decline in oculomotor performance. Relevant brain regions include both brain regions vulnerable to AD pathology and brain regions that are typically spared, suggesting that both “normal” age‐related and pathological mechanisms may be causative for decline in EM control. Our results highlight the importance of taking into account normal age‐related changes when considering EMs as early biomarkers for AD. Further work is needed to better distinguish normal age‐related changes from pathological change.

Association of Olfaction and Microstructural Integrity of Brain Tissue in Community-Dwelling Adults: Atherosclerosis Risk in Communities Neurocognitive Study.

Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. Among 1,418 participants (mean age 76 ± 5 years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9 ± 2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely the hippocampus (β -0.79 [95% CI -0.94 to -0.65] units lower olfaction score per 1 SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared with those with normal cognition (e.g., βhippocampus -0.75 [95% CI -1.02 to -0.49] and -0.44 [95% CI -0.63 to -0.26] for MCI and normal cognition, respectively, p interaction = 0.004). Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with those with MCI may reflect the earlier vs later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.

Posterior parietal cortical areas and recovery after motor stroke: a scoping review.

Brain imaging and electrophysiology have significantly enhanced our current understanding of stroke-related changes in brain structure and function and their implications for recovery processes. In the motor domain, most studies have focused on key motor areas of the frontal lobe including the primary and secondary motor cortices. Time- and recovery-dependent alterations in regional anatomy, brain activity and inter-regional connectivity have been related to recovery. In contrast, the involvement of posterior parietal cortical areas in stroke recovery is poorly understood although these regions are similarly important for important aspects of motor functioning in the healthy brain. Just in recent years, the field has increasingly started to explore to what extent posterior parietal cortical areas might undergo equivalent changes in task-related activation, regional brain structure and inter-regional functional and structural connectivity after stroke. The aim of this scoping review is to give an update on available data covering these aspects and thereby providing novel insights into parieto-frontal interactions for systems neuroscience stroke recovery research in the upper limb motor domain.

Leucocyte telomere length, brain volume and risk of dementia: a prospective cohort study

BackgroundThe evidence regarding the association between leucocyte telomere length (LTL) and brain health is sparse and inconclusive.AimsTo investigate the associations of LTL with brain structure and the risk of dementia...

Correlating MRI-based brain volumetry and cognitive assessment in people with Down syndrome.

Down syndrome (DS) is the most common genetic cause of intellectual disability. Children and adults with DS show deficits in language performance and explicit memory. Here, we used magnetic resonance imaging (MRI) on children and adults with DS to characterize changes in the volume of specific brain structures involved in memory and language and their relationship to features of cognitive-behavioral phenotypes. Thirteen children and adults with the DS phenotype and 12 age- and gender-matched healthy controls (age range 4-25) underwent an assessment by MRI and a psychological evaluation for language and cognitive abilities. The cognitive profile of people with DS showed deficits in different cognition and language domains correlating with reduced volumes of specific regional and subregional brain structures, confirming previous related studies. Interestingly, in our study, people with DS also showed more significant parahippocampal gyrus volumes, in agreement with the results found in earlier reports. The memory functions and language skills affected in studied individuals with DS correlate significantly with the reduced volume of specific brain regions, allowing us to understand DS's cognitive-behavioral phenotype. Our results provide an essential basis for early intervention and the design of rehabilitation management protocols.

Alterations of gut microbiota are associated with brain structural changes in the spectrum of Alzheimer's disease: the SILCODE study in Hainan cohort.

The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown. One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions. The abundance of Lachnospiraceae, Lachnospiracea_incertae_sedis, Fusicatenibacter, and Anaerobutyricum decreased with cognitive ability. Rikenellaceae, Odoribacteraceae, and Alistipes were specifically enriched in the CI group. Mediterraneibacter abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume (p = 0.0214, p = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus. This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.

Preterm birth associated alterations in brain structure, cognitive functioning and behavior in children from the ABCD dataset.

Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition. These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.

Association between polygenic risk for Alzheimer’s disease and brain structure in children and adults

BackgroundThe correlations between genetic risk for Alzheimer’s disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages.MethodsThis study used large existing genome-wide association datasets to calculate polygenic risk score (PRS) for AD in two populations from the UK Biobank (N ~ 23 000) and Adolescent Brain Cognitive Development Study (N ~ 4660) who had multimodal macrostructural and microstructural magnetic resonance imaging (MRI) metrics. We used linear mixed-effect models to assess the strength of the association between AD PRS and multiple MRI metrics of regional brain structures at different stages of life.ResultsCompared to those with lower PRSs, adolescents with higher PRSs had thinner cortex in the caudal anterior cingulate and supramarginal. In the middle-aged and elderly population, AD PRS had correlations with regional structure shrink primarily located in the cingulate, prefrontal cortex, hippocampus, thalamus, amygdala, and striatum, whereas the brain expansion was concentrated near the occipital lobe. Furthermore, both adults and adolescents with higher PRSs exhibited widespread white matter microstructural changes, indicated by decreased fractional anisotropy (FA) or increased mean diffusivity (MD).ConclusionsIn conclusion, our results suggest genetic loading for AD may influence brain structures in a highly dynamic manner, with dramatically different patterns at different ages. This age-specific change is consistent with the classical pattern of brain impairment observed in AD patients.

Association of motor function with cognitive trajectories, risk of mild cognitive impairment, and structural brain differences

AbstractBackgroundThe impact of motor function (MF) on cognitive trajectories and mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association of MF with cognitive trajectories, risk of MCI, and structural brain differences on magnetic resonance imaging (MRI).MethodWithin the Rush Memory and Aging Project, 1,216 cognitively intact participants (mean age: 78.60±7.25 years) were followed for up to 22 years. Baseline global MF was assessed by averaging the z‐scores of 10 motor tests and categorizing these scores tertiles (low middle, and high). Global and domain‐specific cognitive functions – including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed – were assessed annually through 19 cognitive tests. Incident MCI was detected and diagnosed based on standard criteria. A subsample (n = 284) underwent brain MRI and regional structural brain volumes were measured. Data were analyzed using linear mixed‐effects models, Cox regression, and linear regression.ResultAt baseline, global MF scores ranged from 0.46 to 1.82 (mean score: 1.06 ± 0.22). During the follow‐up (median, 6.98 years; interquartile range, 3.08‐10.75 years), 553 participants (45.48%) developed MCI. Compared to participants with high MF, those with low MF had faster decline in global cognition (β = ‐0.05, 95% confidence interval [CI]: ‐0.06 to ‐0.03), episodic memory (β = ‐0.05, 95% CI: ‐0.07 to ‐0.03), semantic memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.02), working memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.03), visuospatial ability (β = ‐0.03, 95% CI: ‐0.04 to ‐0.02), and perceptual speed (β = ‐0.04, 95% CI: ‐0.06 to ‐0.03) over the follow‐up. The multi‐adjusted hazard ratio (95% CI) of MCI was 1.84 (1.41 to 2.42) for the lowest MF tertile compared to the highest. Furthermore, the low MF was related to a significantly greater volume of white matter hyperintensities (β = 0.16, 95% CI: 0.01 to 0.32), but not total brain, white matter, or gray matter volumes (all P &gt;0.05).ConclusionLow MF is associated with faster cognitive decline (including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed) and a moderately increased risk of MCI. Vascular pathologies might play an important role in the MF‐MCI association.

Structural and functional activities of brain in patients with vascular cognitive impairment: A case-controlled magnetic resonance imaging study.

This study aimed to identify abnormal brain regions and imaging indices of vascular cognitive impairment (VCI) and explore specific imaging diagnostic markers of VCI. In this study, 24 patients with VCI were allocated to the VCI group and 25 healthy subjects were assigned to the healthy control (HC) group. Demographic data and neuropsychological test scores were compared using SPSS 25.0. The structural and functional imaging data were post-processed and statistically analyzed using CAT12, DPARSF and SPM12 software, based on the MATLAB platform. The structural and functional indices of gray matter volume (GMV) and regional homogeneity (ReHo) were obtained, and inter-group data were analyzed using an independent-sample t test. Sex, age, years of education, and total brain volume were used as covariates. Compared to the HC group, the GMV of VCI in the VCI group decreased significantly in the rectus muscles of the bilateral gyrus, left superior temporal gyrus, left supplementary motor area (SMA), right insula, right superior temporal gyrus, right anterior cuneiform lobe, and right anterior central gyrus (PRECG) (P < .05, FWE correction), without GMV enlargement in the brain area. ReHo decreased in the right inferior temporal gyrus (ITG), right parahippocampal gyrus, and left temporal pole (middle temporal gyrus, right lingual gyrus, left posterior central gyrus, and right middle temporal gyrus), the areas of increased ReHo were the left caudate nucleus, left rectus gyrus, right anterior cingulate gyrus and lateral cingulate gyrus (P < .05, FWE correction). Correlation analysis showed that the GMV of the left superior temporal gyrus was positively correlated with the Montreal Cognitive Assessment (MoCA) score (P < .05), and the GMV of the right insula was positively correlated with the MESE and long delayed memory scores (P < .05). There was a significant positive correlation between the ReHo and short-term delayed memory scores in the middle temporal gyrus of the left temporal pole (P < .05). The volume of GMV and ReHo decreased in VCI patients, suggesting that impairment of brain structure and function in specific regions is the central mechanism of cognitive impairment in these patients. Meanwhile, the functional indices of some brain regions were increased, which may be a compensatory mechanism for the cognitive impairment associated with VCI.

Plasma TDP-43 levels are associated with neuroimaging measures of brain structure in limbic regions.

We evaluated the relationship between plasma levels of transactive response DNA binding protein of 43kDa (TDP-43) and neuroimaging (magnetic resonance imaging [MRI]) measures of brain structure in aging. Plasma samples were collected from 72 non-demented older adults (age range 60-94 years) in the University of Kentucky Alzheimer's Disease Research Center cohort. Multivariate linear regression models were run with plasma TDP-43 level as the predictor variable and brain structure (volumetric or cortical thickness) measurements as the dependent variable. Covariates included age, sex, intracranial volume, and plasma markers of Alzheimer's disease neuropathological change (ADNC). Negative associations were observed between plasma TDP-43 level and both the volume of the entorhinal cortex, and cortical thickness in the cingulate/parahippocampal gyrus, after controlling for ADNC plasma markers. Plasma TDP-43 levels may be directly associated with structural MRI measures. Plasma TDP-43 assays may prove useful in clinical trial stratification. Plasma transactive response DNA binding protein of 43kDa (TDP-43) levels were associated with entorhinal cortex volume.Biomarkers of TDP-43 and Alzheimer's disease neuropathologic change (ADNC) may help distinguish limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) from ADNC.A comprehensive biomarker kit could aid enrollment in LATE-NC clinical trials.

Restricted language access during childhood affects adult brain structure in selective language regions

Due to the ubiquitous nature of language in the environment of infants, how it affects the anatomical structure of the brain language system over the lifespan is not well understood. In this study, we investigated the effects of early language experience on the adult brain by examining anatomical features of individuals born deaf with typical or restricted language experience in early childhood. Twenty-two deaf adults whose primary language was American Sign Language and were first immersed in it at ages ranging from birth to 14 y participated. The control group was 21 hearing non-signers. We acquired T1-weighted magnetic resonanceimages and used FreeSurfer [B. Fischl,Neuroimage 62, 774-781(2012)]to reconstruct the brain surface. Using an a priori regions of interest (ROI) approach, we identified 17 language and 19 somatomotor ROIs in each hemisphere from the Human Connectome Project parcellation map [M. F. Glasseretal.,Nature 536, 171-178 (2016)]. Restricted language experience in early childhood was associated with negative changes in adjusted grey matter volume and/or cortical thickness in bilateral fronto-temporal regions. No evidence of anatomical differences was observed in any of these regions when deaf signers with infant sign language experience were compared with hearing speakers with infant spoken language experience, showing that the effects of early language experience on the brain language system are supramodal.