Gray Matter Volume Research Articles

Visual Impairment, Eye Conditions, and Diagnoses of Neurodegeneration and Dementia

Vision and eye conditions are associated with increased risk for Alzheimer disease and related dementias (ADRDs), but the nature of the association and the underlying biological pathways remain unclear. If causal, vision would be an important modifiable risk factor with viable population-level interventions. To evaluate potentially causal associations between visual acuity, eye conditions (specifically cataracts and myopia), neuroimaging outcomes, and ADRDs. A cohort and 2-sample bidirectional mendelian randomization (MR) study was conducted using UK Biobank participants and summary statistics from previously published genome-wide association studies on cataract, myopia, and AD. The participants included in the analysis were aged 55 to 70 years without dementia at baseline (calendar years 2006 to 2010), underwent genotyping, and reported on eye conditions; a subset completed visual acuity examinations (n = 69 852-71 429) or brain imaging (n = 36 591-36 855). Data were analyzed from August 15, 2022, through November 28, 2023. Self-reported cataracts, visual acuity, and myopia measured by refraction error. ADRD, AD, and vascular dementia were identified from electronic medical records. Total and regional brain volumes were determined using magnetic resonance imaging. The sample included 304 953 participants (mean [SD] age, 62.1 (4.1) years; 163 825 women [53.72%]); 14 295 (4.69%) had cataracts and 2754 (3.86%) had worse than 20/40 vision. Cataracts (hazard ratio [HR], 1.18; 95% CI, 1.07-1.29) and myopia (HR, 1.35; 95% CI, 1.06-1.70) were associated with a higher hazard of ADRD. In MR analyses to estimate potential causal effects, cataracts were associated with increased risk of vascular dementia (inverse variance-weighted odds ratio [OR], 1.92; 95% CI, 1.26-2.92) but were not associated with increased dementia (OR, 1.21; 95% CI, 0.98-1.50). There were no associations between myopia and dementia. In MR for potential reverse causality, AD was not associated with cataracts (inverse variance-weighted OR, 0.99; 95% CI, 0.96-1.01). Genetic risk for cataracts was associated with smaller total brain (β = -597.43 mm3; 95% CI, -1077.87 to -117.00 mm3) and gray matter (β = -375.17 mm3; 95% CI, -680.10 to -70.24 mm3) volumes, but not other brain regions. In this cohort and MR study of UK Biobank participants, cataracts were associated with increased risk of dementia, especially vascular dementia, and reduced total brain volumes. These findings lend further support to the hypothesis that cataract extraction may reduce the risk for dementia.

Impact of Sleeve Gastrectomy on Brain Structural Integrity.

Potential brain structural differences in people with obesity (PwO) who achieve over or less than 50% excess weight loss (EWL) after sleeve gastrectomy (SG) are currently unknown. We compared measures of gray matter volume (GMV) and white matter (WM) microstructural integrity of PwO who achieved over or less than 50% EWL after SG with a group of controls with obesity (CwO) without a past history of metabolic bariatric surgery. Sixty-two PwO underwent 1.5T MRI scanning: 24 who achieved more than 50% of EWL after SG ("group a"), 18 who achieved less than 50% EWL after SG ("group b"), and 20 CwO ("group c"). Voxel-based morphometry and tract-based spatial Statistics analyses were performed to investigate GMV and WM differences among groups. Multiple regression analyses were performed to investigate relationships between structural and psychological measures. Group a demonstrated significantly lower GMV loss and higher WM microstructural integrity with respect to group b and c in some cortical regions and several WM tracts. Positive correlations were observed in group a between WM integrity and several psychological measures; the lower the WM integrity, the higher the mental distress, emotional dysregulation, and binge eating behavior. The present results gain a new understanding of the neural mechanisms of outcome in patients who undergo SG. We found limited GMV changes and extensive WM microstructural differences between PwO who achieved over or less than 50% EWL after SG, which may be due to higher vulnerability of WM to the metabolic dysfunction present in PwO.

Neural correlates of inattention in adults with ADHD.

In the last two decades, numerous magnetic resonance imaging (MRI) studies have examined differences in cortical structure between individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) and healthy controls. These studies primarily emphasized alterations in gray matter volume (GMV) and cortical thickness (CT). Still, the scientific literature is notably scarce in regard to investigating associations of cortical structure with ADHD psychopathology, specifically inattention within adults with ADHD. The present study aimed to elucidate neurobiological underpinnings of inattention beyond GMV and CT by including cortical gyrification, sulcal depth, and fractal dimension. Building upon the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), cortical structure parameters were investigated using 141 T1-weighted anatomical scans of adult patients with ADHD. All brain structural analyses were performed using the threshold-free cluster enhancement (TFCE) approach and the Computational Anatomy Toolbox (CAT12) integrated into the Statistical Parametric Mapping Software (Matlab Version R2021a). Results revealed significant correlations of inattention in multiple brain regions. Cortical gyrification was negatively correlated, whereas cortical thickness and fractal dimension were positively associated with inattention. The clusters showed widespread distribution across the cerebral cortex, with both hemispheres affected. The cortical regions most prominently affected included the precuneus, para-, pre-, and postcentral gyri, superior parietal lobe, and posterior cingulate cortex. This study highlights the importance of cortical alterations in attentional processes in adults with ADHD. Further research in this area is warranted to elucidate intricacies of inattention in adults with ADHD to potentially enhance diagnostic accuracy and inform personalized treatment strategies.

Functional and structural abnormalities of thalamus in individuals at early stage of schizophrenia

BackgroundThalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. Methods75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. ResultsNo significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. ConclusionsOur findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. Trial registrationClinicalTrials.govNCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.

Differences in gray matter atrophy and functional connectivity between motor subtypes of Parkinson's disease.

Parkinson's disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson's disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson's disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.

Are older adults less generous? Age differences in emotion-related social decision making

In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.

Sex and sobriety: Human brain structure and function in AUD abstinence

Women are drinking alcohol as much as men for the first time in history. Women experience more health-related consequences from alcohol use disorder (AUD), like increased prevalence of alcohol-related cancers, faster progression of alcohol-related liver disease, and greater risk for relapse compared to men. Thus, sex differences in chronic alcohol use pose a substantial public health problem. Despite these evident sex differences, our understanding of how these differences present during alcohol abstinence is limited. Investigations of brain structure and function are therefore critical for disentangling factors that lead to sex differences in AUD abstinence. This review will discuss current human neuroimaging data on sex differences in alcohol abstinence, focusing on structural and functional brain measures. Current structural imaging literature reveals that abstinent men have smaller gray and white matter volume and weaker structural connectivity compared to control men. Interestingly, abstinent women do not show differences in brain structure when compared to controls; instead, abstinent women show a relation between alcohol use and decreased measures of brain structure. Current functional brain studies reveal that abstinent men exhibit greater brain activation and stronger task-based functional connectivity to aversive stimuli than control men, while abstinent women exhibit lesser brain activation and weaker task-based functional connectivity than control women. Together, the current literature suggests that sex differences persist well into alcohol abstinence and impact brain structure and function differently. Understanding how men and women differ during alcohol abstinence can improve our understanding of sex-specific effects of alcohol, which will be critical to augment treatment methods to better serve women.

Brain structural and functional abnormalities in affective network are associated with anxious depression

BackgroundAnxious depression (AD) is a common subtype of major depressive disorder (MDD). Neuroimaging studies of AD have revealed inconsistent and heterogeneous brain alterations with the use of single-model methods. Therefore, it is necessary to explore the pathogenesis of AD using multi-model imaging analyses to obtain more homogeneous and robust results.MethodsOne hundred and eighty-two patients with MDD and 64 matched healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) was used to estimate the gray matter volume (GMV) of all subjects. The GMV differences between the AD and non-anxious depression (NAD) participants were used as regions of interest (ROIs) for subsequent resting state functional connectivity (rs-FC) analyses. Correlation analysis was used to evaluate the associations between clinical symptoms and abnormal function in specific brain areas.ResultsDecreased GMV in the medial frontal gyrus (MFG) and the superior frontal gyrus (SFG) was observed in the AD group compared to the NAD group. Taking the MFG and SFG as ROIs, the rs-FC analysis revealed decreased FC between the left SFG and left temporal pole and between the left SFG and right MFG in the AD group compared to the NAD group. Finally, the FC between the left SFG and left temporal pole was negatively correlated with HAMD-17 scores in the AD group.ConclusionBy combining the GMV and rs-FC models, this study revealed that structural and functional disruption of the affective network may be an important pathophysiology underlying AD. The structural impairment may serve as the foundation of the functional impairment.

Do Cognitive Subtypes Exist in People at Clinical High Risk for Psychosis? Results From the EU-GEI Study.

Cognition has been associated with socio-occupational functioning in individuals at Clinical High Risk for Psychosis (CHR-P). The present study hypothesized that clustering CHR-P participants based on cognitive data could reveal clinically meaningful subtypes. A cohort of 291 CHR-P subjects was recruited through the multicentre EU-GEI high-risk study. We explored whether an underlying cluster structure was present in the cognition data. Clustering of cognition data was performed using k-means clustering and density-based spatial clustering of applications with noise. Cognitive subtypes were validated by comparing differences in functioning, psychosis symptoms, transition outcome, and grey matter volume between clusters. Network analysis was used to further examine relationships between cognition scores and clinical symptoms. No underlying cluster structure was found in the cognitive data. K-means clustering produced "spared" and "impaired" cognition clusters similar to those reported in previous studies. However, these clusters were not associated with differences in functioning, symptomatology, outcome, or grey matter volume. Network analysis identified cognition and symptoms/functioning measures that formed separate subnetworks of associations. Stratifying patients according to cognitive performance has the potential to inform clinical care. However, we did not find evidence of cognitive clusters in this CHR-P sample. We suggest that care needs to be taken in inferring the existence of distinct cognitive subtypes from unsupervised learning studies. Future research in CHR-P samples could explore the existence of cognitive subtypes across a wider range of cognitive domains.

Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer’s Disease

BackgroundIncreased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer’s disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).Objectives1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial.DesignA multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period.SettingAnti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study.ParticipantsA sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers).MeasurementsA linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group.ResultsBaseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH.ConclusionThese results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.

The relationship between work difficulties and physical disability, cognitive and social cognitive impairment and subcortical gray matter atrophy in persons with multiple sclerosis.

Multiple sclerosis (MS) is commonly associated with work difficulties. This study aimed to examine the relationship between work difficulties and physical disability, cognitive and social cognitive impairment, and subcortical gray matter (scGM) atrophy in pwMS. Thirty-three employees with MS underwent assessments with Multiple Sclerosis Work Difficulties Questionnaire-23 MSWDQ-23. Physical disability was measured using EDSS, Timed 25-Foot Walk (T25FW), 2-Minute Walking Test (2-MWT), the Nine-Hole Peg test (N-HPT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Cognitive functions were evaluated with Brief International Cognitive Assessment in MS (BICAMS), social cognition with Facial Emotion Identification (FEI), Reading the Mind in the Eyes Test (RMET), and Empathy Quotient (EQ). Anxiety and depression were assessed using Hospital Anxiety and Depression Scale (HADS). The association between variables was analysed using Spearman's correlation coefficient. GM volumes were calculated from 3T MRI data using Freesurfer, their potential relationship with work difficulties were evaluated through a linear regression model. MSWDQ-23 was strongly correlated with T25FW and MSWS-12 (p < 0.01), moderately correlated with EDSS, 2MWT, HAD, BICAMS, and EQ (p < 0.05). According to the linear regression model the decrease in volumes of total GM and scGM, bilateral Thalamus, bilateral Hippocampus, left Putamen, and right Caudate related with the severity of work difficulties (R²=0.815, p = 0.25). This study provides valuable insights into the multifaceted nature of work difficulties experienced by pwMS. It suggests that not only physical disability but also other factors, such as mood, cognition, empathy, and cortical and subcortical gray matter atrophy may contribute to work difficulties among pwMS.

The ageing central nervous system in multiple sclerosis: the imaging perspective.

The interaction between ageing and multiple sclerosis is complex and carries significant implications for patient care. Managing multiple sclerosis effectively requires an understanding of how ageing and multiple sclerosis impact brain structure and function. Ageing inherently induces brain changes, including reduced plasticity, diminished grey matter volume, and ischaemic lesion accumulation. When combined with multiple sclerosis pathology, these age-related alterations may worsen clinical disability. Ageing may also influence the response of multiple sclerosis patients to therapies and/or their side-effects, highlighting the importance of adjusted treatment considerations. Magnetic resonance MRI is highly sensitive to age- and multiple sclerosis-related processes. Accordingly, MRI can provide insights into the relationship between ageing and multiple sclerosis, enabling a better understanding of their pathophysiological interplay and informing treatment selection. This review summarizes current knowledge on the immuno-pathological and MRI aspects of ageing in the central nervous system in the context of multiple sclerosis. Starting from immunosenescence, ageing-related pathological mechanisms, and specific features like enlarged Virchow-Robin spaces, this review then explores clinical aspects, including late-onset multiple sclerosis, the influence of age on diagnostic criteria, and comorbidity effects on imaging features. The role of MRI in understanding neurodegeneration, iron dynamics, and myelin changes influenced by ageing and how MRI can contribute to defining treatment effects in ageing multiple sclerosis patients, are also discussed.

Left Frontoparietal Control Network Connectivity Moderates the Effect of Amyloid on Cognitive Decline in Preclinical Alzheimer’s Disease: The A4 Study

BackgroundStronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer’s disease related pathology and neurodegeneration in smaller cohort studies.ObjectivesWe investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).DesignLongitudinal mixed.SettingThe Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study.ParticipantsA sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive).MeasurementsGlobal cognitive performance (Preclinical Alzheimer’s Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version.ResultsMixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p =.025) such that stronger connectivity was associated with reduced Aβ-related cognitive decline.ConclusionsOur results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.

Correlation of brain tissue volume loss with inflammatory biomarkers IL1β, P-tau, T-tau, and NLPR3 in the aging cognitively impaired population.

Blood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people. This study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1β), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aβ42 (mAβ), oligomeric Aβ42 (oAβ), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses. GMV and gwBTV significantly decreased as the levels of IL1β and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1β, P-tau, and T-tau in the hippocampus. Specifically, IL1β and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3. The observed association between brain tissue volume loss and elevated levels of IL1β and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1β and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.

Association of sarcopenia with regional brain atrophy and white matter lesions in a general older population: the Hisayama Study.

Sarcopenia has been reported to be associated with cognitive decline and the risk of dementia. However, few studies have addressed the association between sarcopenia and brain morphological changes in the general population. A total of 1373 community-dwelling participants aged ≥ 65years underwent brain MRI. Sarcopenia was defined based on the Asian Working Group for Sarcopenia's criteria. The pattern of regional gray matter volume loss associated with sarcopenia were assessed using a voxel-based morphometry (VBM) analysis. Regional brain volumes, intracranial volumes (ICV), and white matter lesions volumes (WMLV) were also measured using FreeSurfer. An analysis of covariance was used to examine the associations of sarcopenia with regional brain volumes in proportion to ICV. Of the participants, 112 had sarcopenia. The participants with sarcopenia had significantly lower total brain volume/ICV and total gray matter volume/ICV and higher WMLV/ICV than those without sarcopenia after adjusting for confounders. In VBM, sarcopenia was associated with lower gray matter volume in the frontal lobe, insula, cingulate gyrus, hippocampus, amygdala, and basal ganglia. Using FreeSurfer, we confirmed that the participants with sarcopenia had significantly lower frontal, insular, cingulate, and hippocampal volumes than those without sarcopenia. The current study showed that participants with sarcopenia had significantly lower volume in the frontal lobe, insula, cingulate, and hippocampus and higher WMLV than participants without sarcopenia. As these brain regions are likely to play an important role in cognitive function, these changes may suggest a shared underlying mechanism for the progression of sarcopenia and cognitive decline.

Spatiotemporal Progression Patterns of Dopamine Availability and Deep Gray Matter Volume in Parkinson Disease-Related Cognitive Impairment.

Cognitive impairment is a frequent nonmotor symptom in patients with Parkinson disease (PD), and early cognitive decline is often attributed to dopaminergic system dysfunction. We aimed to explore spatiotemporal progression patterns of striatal dopamine availability and regional brain volume based on cognitive status among patients with PD. This retrospective, cross-sectional study included patients with newly diagnosed PD who were not taking medication for this condition who visited a university-affiliated hospital in Seoul between January 2018 and December 2020. Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or PD dementia (PDD) based on Seoul Neuropsychological Screening Battery-II, which includes 31 subsets covering activities of daily living and 5 cognitive domains. They all had brain imaging with MRI and PET with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane at baseline. Subsequently, standardized uptake value ratios (SUVRs) for regional dopamine availability and regional gray matter volumes were obtained using automated segmentation. These metrics were compared across cognitive status groups, and spatiotemporal progression patterns were analyzed using the Subtype and Stage Inference machine learning technique. Among 168 patients (mean age, 73.3 ± 6.1 years; 81 [48.2%] women), 65 had PD-NC, 65 had PD-MCI, and 38 had PDD. Patients with PD-MCI exhibited lower SUVRs (3.61 ± 1.31, p < 0.001) in the caudate than patients with PD-NC (4.43 ± 1.21) but higher SUVRs than patients with PDD (2.39 ± 1.06). Patients with PD-NC had higher thalamic SUVRs (1.55 ± 0.16, p < 0.001) than patients with both PD-MCI (1.45 ± 0.16) and PDD (1.38 ± 0.19). Regional deep gray matter volumes of the caudate (p = 0.015), putamen (p = 0.012), globus pallidus (p < 0.001), thalamus (p < 0.001), hippocampus (p < 0.001), and amygdala (p < 0.001) were more reduced in patients with PD-MCI or PDD than in patients with PD-NC, and the SUVR of the caudate correlated with caudate volume (r = 0.187, p = 0.015). Hippocampal atrophy was the initial change influencing cognitive impairment. The reduced dopamine availability of the thalamus preceded reductions in volume across most deep gray matter regions. Our finding underscores the association between decreased dopamine availability and volume of the caudate and thalamus with cognitive dysfunction in PD. The dopamine availability of the caudate and thalamus was reduced before the volume of the caudate and thalamus was decreased, highlighting the spatiotemporal association between dopaminergic and structural pathology in cognitive impairment in PD.

18F-Flortaucipir (AV1451) imaging identifies grey matter atrophy in retired athletes

BackgroundThe long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are neededObjectiveThis study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning.MethodsFormer contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [18F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels).Results47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (− 0.37 ± 0.41 vs. − 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = − .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played.ConclusionA higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration.

MRI-informed machine learning-driven brain age models for classifying mild cognitive impairment converters.

Brain age model, including estimated brain age and brain-predicted age difference (brain-PAD), has shown great potentials for serving as imaging markers for monitoring normal ageing, as well as for identifying the individuals in the pre-diagnostic phase of neurodegenerative diseases. This study aimed to investigate the brain age models in normal ageing and mild cognitive impairments (MCI) converters and their values in classifying MCI conversion. Pre-trained brain age model was constructed using the structural magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 609). The tested brain age model was built using the baseline, 1-year and 3-year follow-up MRI data from normal ageing (NA) adults (n = 32) and MCI converters (n = 22) drew from the Open Access Series of Imaging Studies (OASIS-2). The quantitative measures of morphometry included total intracranial volume (TIV), gray matter volume (GMV) and cortical thickness. Brain age models were calculated based on the individual's morphometric features using the support vector machine (SVM) algorithm. With comparable chronological age, MCI converters showed significant increased TIV-based (Baseline: P = 0.021; 1-year follow-up: P = 0.037; 3-year follow-up: P = 0.001) and left GMV-based brain age than NA adults at all time points. Higher brain-PAD scores were associated with worse global cognition. Acceptable classification performance of TIV-based (AUC = 0.698) and left GMV-based brain age (AUC = 0.703) was found, which could differentiate the MCI converters from NA adults at the baseline. This is the first demonstration that MRI-informed brain age models exhibit feature-specific patterns. The greater GMV-based brain age observed in MCI converters may provide new evidence for identifying the individuals at the early stage of neurodegeneration. Our findings added value to existing quantitative imaging markers and might help to improve disease monitoring and accelerate personalized treatments in clinical practice.

Hyperacusis in Tinnitus Individuals Is Associated with Smaller Gray Matter Volumes in the Supplementary Motor Area Regardless of Hearing Levels.

Recent evidence suggests a connection between hyperacusis and the motor system of the brain. For instance, our recent study reported that hyperacusis in participants with tinnitus and hearing loss is associated with smaller gray matter volumes in the supplementary motor area (SMA). Given that hearing loss can affect gray matter changes in tinnitus, this study aimed to determine if the changes reported in our previous findings of smaller SMA gray matter volumes in hyperacusis persist in the absence of hearing loss. Data for this study were gathered from four prior studies conducted between 2004 and 2019 at the University Medical Centre Groningen (UMCG). A total of 101 participants with tinnitus and either clinically normal hearing (normal hearing with tinnitus or NHT, n = 35) or bilateral sensorineural hearing loss (hearing loss with tinnitus or HLT, n = 66) were included across four studies. Hyperacusis was determined by a score of ≥22 on the Hyperacusis Questionnaire (HQ). In the NHT group, 22 (63%) participants scored ≥22 on the HQ (NHT with hyperacusis: mean age 44.1 years, 12 females), while in the HLT group, 25 (38%) participants scored ≥22 on the HQ (HLT with hyperacusis: mean age 59.5 years, 10 females). The 2 × 2 between-group ANOVAs revealed that hyperacusis is associated with smaller SMA gray matter volumes, regardless of hearing levels. Notably, the smaller SMA gray matter volumes in hyperacusis were primarily influenced by the attentional subscales of the HQ. The association between hyperacusis and the motor system may indicate a constant alertness to sounds and a readiness for motor action.

Multimodal abnormalities of brain structures in adolescents and young adults with major depressive disorder: An activation likelihood estimation meta-analysis.

Major depressive disorder (MDD) in adolescents and young adults contributes significantly to global morbidity, with inconsistent findings on brain structural changes from structural magnetic resonance imaging studies. Activation likelihood estimation (ALE) offers a method to synthesize these diverse findings and identify consistent brain anomalies. To identify consistent brain structural changes in adolescents and young adults with MDD using ALE meta-analysis. We performed a comprehensive literature search in PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure databases for neuroimaging studies on MDD among adolescents and young adults published up to November 19, 2023. Two independent researchers performed the study selection, quality assessment, and data extraction. The ALE technique was employed to synthesize findings on localized brain function anomalies in MDD patients, which was supplemented by sensitivity analyses. Twenty-two studies comprising fourteen diffusion tensor imaging (DTI) studies and eight voxel-based morphometry (VBM) studies, and involving 451 MDD patients and 465 healthy controls (HCs) for DTI and 664 MDD patients and 946 HCs for VBM, were included. DTI-based ALE demonstrated significant reductions in fractional anisotropy (FA) values in the right caudate head, right insula, and right lentiform nucleus putamen in adolescents and young adults with MDD compared to HCs, with no regions exhibiting increased FA values. VBM-based ALE did not demonstrate significant alterations in gray matter volume. Sensitivity analyses highlighted consistent findings in the right caudate head (11 of 14 analyses), right insula (10 of 14 analyses), and right lentiform nucleus putamen (11 of 14 analyses). Structural alterations in the right caudate head, right insula, and right lentiform nucleus putamen in young MDD patients may contribute to its recurrent nature, offering insights for targeted therapies.