Changes In Cortical Thickness Research Articles

Alterations in cortical thickness of frontoparietal regions in patients with social anxiety disorder

Although functional changes of the frontal and (para)limbic area for emotional hyper-reactivity and emotional dysregulation are well documented in social anxiety disorder (SAD), prior studies on structural changes have shown mixed results. This study aimed to identify differences in cortical thickness between SAD and healthy controls (CON). Thirty-five patients with SAD and forty-two matched CON underwent structural magnetic resonance imaging. A vertex-based whole brain and regional analyses were conducted for between-group comparison. The whole-brain analysis revealed increased cortical thickness in the left insula, left superior parietal lobule, left superior temporal gyrus, and left frontopolar cortex in patients with SAD compared to CON, as well as decreased thickness in the left superior/middle frontal gyrus and left fusiform gyrus in patients (after multiple-correction). The results from the ROI analysis did not align with these findings at the statistically significant level after multiple corrections. Changes in cortical thickness were not correlated with social anxiety symptoms. While consistent results were not obtained from different analysis methods, the results from the whole-brain analysis suggest that patients with SAD exhibit distinct neural deficits in areas involved in salience, attention, and socioemotional processing.

Childhood engagement in cognitively stimulating activities moderates relationships between brain structure and cognitive function in adulthood

Greater engagement in cognitively stimulating activities (CSA) during adulthood has been shown to protect against neurocognitive decline, but no studies have investigated whether CSA during childhood protects against effects of brain changes on cognition later in life. The current study tested the moderating role of childhood CSA in the relationships between brain structure and cognitive performance during adulthood. At baseline (N=250) and 5-year follow-up (N=204) healthy adults aged 20–80 underwent MRI to assess four structural brain measures and completed neuropsychological tests to measure three cognitive domains. Participants were categorized into low and high childhood CSA based on self-report questionnaires. Results of multivariable linear regressions analyzing interactions between CSA, brain structure, and cognition showed that higher childhood CSA was associated with a weaker relationship between cortical thickness and memory at baseline, and attenuated the effects of change in cortical thickness and brain volume on decline in processing speed over time. These findings suggest higher CSA during childhood may mitigate the effects of brain structure changes on cognitive function later in life.

Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review.

Electroconvulsive therapy (ECT) is one of the most studied and validated available treatments for severe or treatment-resistant depression. However, little is known about the neural mechanisms underlying ECT. This systematic review aims to critically review all structural magnetic resonance imaging studies investigating longitudinal cortical thickness (CT) changes after ECT in patients with unipolar or bipolar depression. We performed a search on PubMed, Medline, and Embase to identify all available studies published before April 20, 2023. A total of 10 studies were included. The investigations showed widespread increases in CT after ECT in depressed patients, involving mainly the temporal, insular, and frontal regions. In five studies, CT increases in a non-overlapping set of brain areas correlated with the clinical efficacy of ECT. The small sample size, heterogeneity in terms of populations, comorbidities, and ECT protocols, and the lack of a control group in some investigations limit the generalisability of the results. Our findings support the idea that ECT can increase CT in patients with unipolar and bipolar depression. It remains unclear whether these changes are related to the clinical response. Future larger studies with longer follow-up are warranted to thoroughly address the potential role of CT as a biomarker of clinical response after ECT.

Longitudinal brain structure changes in Parkinson's disease: A replication study.

An existing major challenge in Parkinson's disease (PD) research is the identification of biomarkers of disease progression. While magnetic resonance imaging is a potential source of PD biomarkers, none of the magnetic resonance imaging measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations. This study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson's Progression Markers Initiative (PPMI). Using 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between structural changes and cognitive decline. We compared our findings to the results in the original study. (1) Similarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance. Despite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data is added to PPMI.

Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

A pilot study of longitudinal changes in neurocognition, white matter hyperintensities, and cortical thickness in atrial fibrillation patients following catheter ablation vs medical management

BackgroundCerebral microembolization and atrophy complicate atrial fibrillation (AF). ObjectivesWe aimed to compare changes in neuroimaging findings between AF patients treated with catheter ablation and those treated with medical therapy. MethodsIn this pilot study, we evaluated differences in the change in regional white matter hyperintensity burden (WMHb) and cognitive function from baseline to 6-weeks and 1-year in patients treated with AF ablation (ABL, n=12) and patients treated with medical management alone (MM, n=11). Change in cortical thickness in Alzheimer’s Disease (AD)-risk, aging-associated or shared AD-risk/aging regions was also compared between groups. ResultsThe mean age was 69.7±5.0, 78% of patients were male, 39% had persistent AF, and all received oral anticoagulation. There were no significant differences between groups in the change in cognitive function. At 6-weeks, there were no significant differences in periventricular WMHb changes between groups (0.00 vs. 0.04; p=0.12), but changes in attention/concentration were inversely correlated with periventricular (p=0.01) and total WMHb (p=0.03). MM patients demonstrated significantly greater cortical thinning in AD-risk regions from baseline to 1-year (p=0.003). ConclusionsAF patients who underwent ablation demonstrated less cortical thinning in regions associated with AD risk than patients treated with medical therapy. Larger, prospective studies are needed to better understand the relationship between AF therapies and the development of cognitive decline.

Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients

Introduction: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. Methods: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. Results: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. Conclusion: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Methodological challenges of measuring brain volumes and cortical thickness in idiopathic normal pressure hydrocephalus with a surface-based approach.

Identifying disease-specific imaging features of idiopathic Normal Pressure Hydrocephalus (iNPH) is crucial to develop accurate diagnoses, although the abnormal brain anatomy of patients with iNPH creates challenges in neuroimaging analysis. We quantified cortical thickness and volume using FreeSurfer 7.3.2 in 19 patients with iNPH, 28 patients with Alzheimer's disease (AD), and 30 healthy controls (HC). We noted the frequent need for manual correction of the automated segmentation in iNPH and examined the effect of correction on the results. We identified statistically significant higher proportion of volume changes associated with manual edits in individuals with iNPH compared to both HC and patients with AD. Changes in cortical thickness and volume related to manual correction were also partly correlated with the severity of radiological features of iNPH. We highlight the challenges posed by the abnormal anatomy in iNPH when conducting neuroimaging analysis and emphasise the importance of quality checking and correction in this clinical population.

The Relationship between History of Traumatic Brain Injury and Longitudinal Changes in Cortical Thickness among Patients with Alzheimer’s Disease

The Relationship between History of Traumatic Brain Injury and Longitudinal Changes in Cortical Thickness among Patients with Alzheimer’s Disease

A systematic review of the impact of type 2 diabetes on brain cortical thickness.

Type 2 diabetes (T2D) has been linked to cognitive impairment and dementia, but its impact on brain cortical structures in individuals prior to or without cognitive impairment remains unclear. We conducted a systematic review of 2,331 entries investigating cerebral cortical thickness changes in T2D individuals without cognitive impairment, 55 of which met our inclusion criteria. Most studies (45/55) reported cortical brain atrophy and reduced thickness in the anterior cingulate, temporal, and frontal lobes between T2D and otherwise cognitively healthy controls. However, the balance of studies (10/55) reported no significant differences in either cortical or total brain volumes. A few reports also noticed changes in the occipital cortex and its gyri. As part of the reports, less than half of studies (18/55) described a correlation between T2D and hippocampal atrophy. Variability in sample characteristics, imaging methods, and software could affect findings on T2D and cortical atrophy. In conclusion, T2D appears linked to reduced cortical thickness, possibly impacting cognition and dementia risk. Microvascular disease and inflammation in T2D may also contribute to this risk. Further research is needed to understand the underlying mechanisms and brain health implications.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking. Therefore, we recruited 26 SFN patients and 25 age- and sex-matched healthy controls to conduct voxel-based- and surface-based morphometry. Across all patients, we found reduced GMV in widespread frontal regions, left caudate, insula and superior parietal lobule. Surface-based morphometry analysis revealed reduced CT in the right precentral gyrus of SFN patients. In a region-based approach, patients had reduced GMV in the left caudate. Since pathogenic gain-of-function variants in voltage-gated sodium channels (Nav) have been associated with SFN pathophysiology, we explored brain morphological patterns in a homogenous subsample of patients carrying rare heterozygous missense variants. Whole brain- and region-based approaches revealed GMV reductions in the bilateral caudate for Nav variant carriers. Further research is needed to analyze the specific role of Nav variants for structural brain alterations. Together, we conclude that SFN patients have specific GMV and CT alterations, potentially forming potential new central biomarkers for this condition. Our results might help to better understand underlying or compensatory mechanisms of chronic pain perception in the future. PerspectiveThis study reveals structural brain changes in small-fiber neuropathy (SFN) patients, particularly in frontal regions, caudate, insula, and parietal lobule. Notably, individuals with SFN and specific Nav variants exhibit bilateral caudate abnormalities. These findings may serve as potential central biomarkers for SFN and provide insights into chronic pain perception mechanisms.

Androgen deprivation increases frontopolar cortical thickness in prostate cancer patients: an effect of early neurodegeneration?

Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT leads to altered testosterone levels that may affect brain morphology as well as cognition. Considering the reliability of cortical thickness (CT) as a marker of cognitive and brain changes, e.g., in Alzheimer's disease, we assessed the impacts of ADT on CT and working memory. Thirty men with non-metastatic prostate cancer receiving ADT and 32 patients not receiving ADT (controls or CON), matched in age and years of education, participated in N-back task and quality-of-life (QoL) assessments as well as brain imaging at baseline and prospectively at 6 months. Imaging data were processed with published routines to estimate CT and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. ADT and CON did not differ in N-back performance or QoL across time points. Relative to CON, patients receiving ADT showed significantly higher frontopolar cortex (FPC) CT at 6-month follow-up vs. baseline. Follow-up vs. baseline FPC CT change correlated negatively with changes in 2-back correct response rate and in testosterone levels across all participants. In mediation analysis, FPC CT change mediated the association between testosterone level change and 2-back accuracy rate change. Increases in FPC CT following 6 months of ADT may reflect early neurodegenerative changes in response to androgen deprivation. While no significant impact on working memory or QoL was observed over 6 months, further research of longer duration of treatment is warranted to unravel the full spectrum of cognitive and neural consequences of ADT in prostate cancer patients.

Early- to mid-term outcome of a short, cementless, titanium, flat, tapered stem for primary total hip arthroplasty: an independent series.

This study aims to: (1) describe perioperative complications amongst patients who underwent primary total hip arthroplasty (THA) using a short cementless, titanium, flat, tapered stem; (2) estimate this stem's early- to mid-term survival; (3) identify factors associated with revision arthroplasty; and (4) describe femoral remodelling at minimum 6 years postoperatively. A retrospective review of consecutive patients who underwent THA using a Taperloc Microplasty stem (Zimmer-Biomet, Warsaw, Indiana, USA) with minimum 2-year follow-up was performed. Surgeries were performed by 1 of 6, non-designer, arthroplasty surgeons between 2014 and 2018. Outcomes included perioperative complications including revision arthroplasty, and survival. Cox analysis was used to analyse the effect of different factors on risk of revision arthroplasty. Radiographs with 6-year follow-up served to describe femoral remodelling. In 1205 patients, followed for 5.1 ± 1.4 years, the incidence of perioperative complication was 5.2% for which 29 patients (2.4%) required revision arthroplasty. The 5- and 7-year survival rates were 97.8% (95% CI, 96.9-98.5) and 97.0% (95% CI, 95.6-98.0), respectively. The only factor associated with revision arthroplasty was proximal femur morphology, as per Dorr classification (HR 1.24 [95%CI, 1.09-1.41]; p = 0.005). During radiographic assessment, 12% of patients showed ⩾25% of relative change in cortical thickness in Gruen zones 3 or 5. We observed calcar remodelling in 50% of radiographs while 10% showed presence of a pedestal sign. The 7-year survivorship of the Taperloc Microplasty stem is within National Institute for Health and Care Excellence (NICE) guidelines. Patients ⩽65 years with osteoarthritis and Dorr A/B femoral morphology may be ideal candidates for THA with this stem. Femoral remodelling is common and not associated with adverse outcome.

Changes in cortical thickness along the Alzheimer disease continuum in people with Down syndrome

AbstractBackgroundTriplication of the APP allele in Down syndrome (DS) leads to excess amyloid production and Alzheimer’s disease (AD) related cognitive decline. Key biomarkers (amyloid, tau, neurodegeneration) can identify pathological processes that occur before clinical symptoms and more precisely stage adults with DS along the AD continuum. Previous research has used changes in cortical thickness (CT) as an indicator of neurodegeneration in autosomal‐dominant AD1, but not DS‐related AD. It is unclear when and where cortical thinning occurs along the AD continuum in DS and if these differences are associated with increasing AD pathology.MethodCross‐sectional analysis compared DS participants from the Alzheimer Biomarkers Consortium‐Down Syndrome (106 amyloid‐/cognitively unimpaired, nonclinical, 20% reserved for receiver‐operating characteristic, ROC, analyses; 45 amyloid+/cognitively unimpaired, preclinical; 27 amyloid+/cognitively impaired, clinical) who had amyloid positron emission tomography and magnetic resonance imaging (MRI). Amyloid positivity was defined using standardized uptake value ratio (partial volume corrected) cortical mean values (1.42/1.19 for PIB/AV452) and impairment was based on consensus diagnosis. CT differences between nonclinical and clinical groups were calculated in FreeSurfer v5.3 for multiple thresholds (p<.05/.01/.005/.001/.0005/.0001) using a cluster‐wise false discovery rate of .001, corrected across hemispheres, after controlling for age and sex. CT values were extracted for each threshold and used in ROC analyses (nonclinical reserved participants compared against preclinical and preclinical compared against clinical) to identify key cortical regions that best discriminated amyloid positivity and between unimpaired and impaired.ResultSignificant decreases in parietal and inferior temporal CT were observed between nonclinical and clinical (Figures 1 and 2). ROC analyses identified regions in the left (threshold .05) and right (threshold .005) hemispheres that best differentiated nonclinical from preclinical. Observed area under the curves (AUCs) of .772 and .830 exceeded those previously reported for autosomal‐dominant AD (.547/.540)1. Analyses differentiating preclinical from clinical observed AUCs of .786 for left (threshold .0005) and .770 for right (threshold .0005) hemispheres.ConclusionCT differences primarily within posterior cortical regions differentiated adults with DS by amyloid status and cognitive impairment. CT differences were more diffuse for amyloid positivity but more focal for impairment.1. Dincer (2020). NeuroImage: Clinical, 28, 102491.2. Su (2019). Alzheimer’s Dement, 11, 180‐190.

Computerized Games versus Crosswords Training in Mild Cognitive Impairment: The COG‐IT trial

AbstractBackgroundMild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in MCI is unclear.MethodIn a two‐site, single‐blinded, 78‐week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home‐based, computerized training with Web‐based cognitive games or Web‐based crossword puzzles, followed by six booster sessions. In mixed‐model analyses, the primary outcome was change from baseline in the 11‐item Alzheimer’s Disease Assessment Scale‐Cognitive (ADAS‐Cog) score, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score and Functional Activities Questionnaire score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.ResultAmong 107 participants (n = 51 [games]; n = 56 [crosswords]), ADAS‐Cog11 score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, 21.44; 95% CI 22.83 to 20.06; P = 0.04). From baseline to week 78, mean ADAS‐Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, 22.45; SE, 0.89; 95% CI 24.21 to 20.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, 21.08; 95% CI 21.97 to 20.18, p = 0.02). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI 0.51 to 67.63, p < .05 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04, p = .02 [cortical thickness]).ConclusionHome‐based computerized training with crosswords demonstrated superior efficacy to games at 78 weeks. Common directionality was observed in the primary outcome of ADAS‐Cog (cognition) and the secondary outcomes of FAQ (function) score and changes in MRI hippocampal volume and cortical thickness (neurodegeneration). If these effects are replicated and expanded in future trials with the inclusion of a control group that does not receive cognitive training, crossword puzzles training could become a home‐based, scalable, cognitive enhancement tool for individuals with MCI.

Metformin and dietary restriction pathway are associated with neuroprotection in Alzheimer’s disease context. A key role for glial autophagy

AbstractBackgroundThe global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to premature brain aging. The inflammation and insulin resistance interplay represent a potential target to prevent neurodegeneration.MethodWe evaluated the effect of the antidiabetic drug metformin‐considered a dietary restriction (DR) mimetic‐ on patients enrolled in ADNI, an observational and longitudinal study including patients from all around the world. We employed data from patients diagnosed with mild cognitive impairment (MCI) due to AD and we performed a principal component analysis focusing on biomarkers associated to AD measured in cerebrospinal fluid.We analyzed memory performance and hippocampal alterations in a model of AD, the PDAPP‐J20 transgenic mouse (Tg) and evaluated the effects of a periodic DR protocol (3 cycles of 40% DR for 5 days and ad libitum diet for 9 days).ResultMCI metformin‐treated patients were characterized as subjects with a better CSF biomarkers profile than the mean population of MCI patients (p<0.05). Control subjects and T2D patients were paired by age, gender, ApoE allele and education, defining three groups: MCI, MCI+T2D and MCI+T2D+metformin. We evaluated the effect of T2D and metformin treatment employing the PACC score and composites defined from standardized ADNI variables to evaluate the memory/learning function. We found that MCI+T2D patients have a worse cognitive performance than MCI patients (p<0.01), but this effect was absent in MCI+T2D+metformin patients. These cognitive variations were associated with changes in cortical thickness and hippocampal volume (p<0.001). Our study shows a beneficial effect of metformin treatment on cognitive performance, CSF biomarkers profile and neuroanatomical measures in MCI due to AD patients.We observed cognitive impairment, low adult neurogenesis and progressive Aβ deposition in the hippocampus of Tg mice. Periodic DR was associated to cognitive improvement, increased hippocampal neurogenesis, and reduced hippocampal amyloid load; we found that autophagy is modulated in Tg mice with a high proportion of LC3/Aβ colocalizing in astrocytes, probably contributing to the reduction in amyloid plaques associated to DR.ConclusionOur data suggest that metformin and DR may be potential interventions to promote healthy aging and prevent dementia.

Association between mild behavioral impairment and hippocampal structural covariance in amnestic mild cognitive impairment

AbstractBackgroundOur previous work reported that mild cognitive impairment (MCI) patients with multiple mild behavioral impairment (MBI) domain symptoms (complex group) revealed a higher risk of developing Alzheimer’s disease (AD) compared with those with no MBI symptoms (asymptomatic group) and cortical thinning in the parietal and frontal areas. However, MCI patients with only affective dysregulation (affective dysregulation group) were not associated with the risk of AD and revealed relative cortical thickening (Yoon EJ, Front Aging Neurosci 2023). To clarify relationships of cortical thickness changes and risk of progression to AD in MCI patients, we compared structural covariance patterns between hippocampal volume and cortical thickness among the MBI subgroups.MethodA total 201 older adults with amnestic MCI were classified based on profiles of MBI domain symptoms into asymptomatic, affective dysregulation, and complex groups. The FreeSurfer was used to estimate cortical thickness and volumes of hippocampal subfields (Fig 1). A vertex‐wise general linear interaction model was used to compare group map of covariance between volumes of hippocampus subfields and thickness at each of vertices. Correlations between the thickness in regions showing significant group differences and mini‐mental state examination (MMSE) scores were also assessed.ResultIn the affective dysregulation group, the structural covariance of left CA1, CA4/DG and molecular layer were increased in the left superior and inferior parietal cortex (Fig 2a), and the thickness of this region showed positive correlation with MMSE (spearman’s rho = 0.302, p‐value = 0.046). The structural covariance of left hippocampal tail for the affective dysregulation group was increased in left lateral occipital cortex, and those for the complex group was increased in left inferior parietal and lateral occipital cortex compared with the asymptomatic group (Fig 2b). Also, the complex group revealed decreased structural covariance of right subiculum with left rostral middle frontal cortex (Fig 2c).ConclusionOur findings suggest that the lateral parietal area might have an important role in compensatory mechanisms in the affective dysregulation group. On the other hand, the complex group may be associated with more advanced stages of disease in which the patterns of increased covariance of hippocampal subfields were disappeared or inversed.

Diffusion MRI track cortical microstructural changes over time during the early stages of the Alzheimer’s disease continuum

AbstractBackgroundMarkers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Previous cross‐sectional investigations suggested that diffusion MRI (dMRI) can provide metrics sensitive to cortical microstructural alteration linked to multiple aspects of the AD pathological cascade including Aß‐accumulation and astrocytic activity. However, currently little evidence is available regarding the ability of dMRI in tracking changes over time.MethodMean diffusivity (MD) was computed from dMRI data acquired from 363 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐1 study. Each participant underwent multiple dMRI scan (range 2‐4 scans) and was classified as Aß‐negative/tau‐negative, Aß‐positive/tau‐negative, and Aß‐positive/tau‐positive based on CSF levels of Aß42/40 and ptau‐181. Rates of changes in MD, cortical thickness and plasma level of GFAP were computed in a linear mixed effect framework. Cortical regional values of MD were compared across biomarkers‐defined groups as well as to rates of change of GFAP.ResultAnalyses of MD revealed widespread differences in rates of change already between Aß‐negative/tau‐negative and Aß‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aß accumulation (fig.1). Further, analyses focusing on two composite ROIs, one encompassing regions that accumulate Aß early in the disease process and a temporal meta‐ROI, confirmed that rates of change in MD significantly differed between groups even when cortical thickness was included in the model (Ps<0.05,fig.2). Regional MD rates of change in both neocortical temporal areas and key regions for Aß‐accumulation, were also positively correlated with rates of change in GFAP (fig.3). Such result was supported by the analysis based on the two meta‐ROIs which confirmed the positive association between rates of change GFAP and MD.ConclusionMean diffusivity from dMRI is able to track cortical microstructural changes over time and to differentiate trajectories even during the early stages of the AD pathological cascade. The association between rates of change of MD and rates of change of GFAP suggested dMRI might reflect microstructural changes related to the astrocytic response to AD pathology. dMRI might help monitoring the effects of disease‐modifying therapies (e.g. Ab immunotherapies) in clinical trials.

Diffusion MRI track cortical microstructural changes over time during the early stages of the Alzheimer’s disease continuum

AbstractBackgroundMarkers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Previous cross‐sectional investigations suggested that diffusion MRI (dMRI) can provide metrics sensitive to cortical microstructural alteration linked to multiple aspects of the AD pathological cascade including Aβ‐accumulation and astrocytic activity. However, currently little evidence is available regarding the ability of dMRI in tracking changes over time.MethodsMean diffusivity (MD) was computed from dMRI data acquired from 363 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐1 study. Each participant underwent multiple dMRI scan (range 2‐4 scans) and was classified as Aβ‐negative/tau‐negative, Aβ‐positive/tau‐negative, and Aβ‐positive/tau‐positive based on CSF levels of Aβ42/40 and ptau‐181. Rates of changes in MD, cortical thickness and plasma level of GFAP were computed in a linear mixed effect framework. Cortical regional values of MD were compared across biomarkers‐defined groups as well as to rates of change of GFAP.ResultsAnalyses of MD revealed widespread differences in rates of change already between Aβ‐negative/tau‐negative and Aβ‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation (fig.1). Further, analyses focusing on two composite ROIs, one encompassing regions that accumulate Aβ early in the disease process and a temporal meta‐ROI, confirmed that rates of change in MD significantly differed between groups even when cortical thickness was included in the model (Ps<0.05,fig.2). Regional MD rates of change in both neocortical temporal areas and key regions for Aβ‐accumulation, were also positively correlated with rates of change in GFAP (fig.3). Such result was supported by the analysis based on the two meta‐ROIs which confirmed the positive association between rates of change GFAP and MD.ConclusionMean diffusivity from dMRI is able to track cortical microstructural changes over time and to differentiate trajectories even during the early stages of the AD pathological cascade. The association between rates of change of MD and rates of change of GFAP suggested dMRI might reflect microstructural changes related to the astrocytic response to AD pathology. dMRI might help monitoring the effects of disease‐modifying therapies (e.g. Ab immunotherapies) in clinical trials.

Longitudinal cortical thinning is associated with cognitive decline in MCI and Alzheimer’s disease in the Korean population

AbstractUndAlzheimer’s disease (AD) is characterized by cognitive dysfunction likely secondary to progressive neurodegeneration in the brain. However, to what extent regional cortical thickness (CT) changes are related to cognitive decline in the Asian population remains unclear.MethodWe measured CT using Freesurfer v6 from T1‐weighted magnetic resonance imaging (MRI) data in 603 Korean participants, including 71 young and 288 old cognitively unimpaired (CU young and CU old), 149 with mild cognitive impairment (MCI), and 92 AD from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). Cognitive function of each participant was quantified by the MMSE. MRI and cognitive data were acquired at baseline (n = 603) and a 2‐year follow‐up visit (n = 380). Linear mixed‐effect models were used to estimate diagnosis group, time, and group‐by‐time interaction effects on CT measurements, with age, sex, and education as covariates. Pearson’s correlations between CT measurements and MMSE total score were computed, corrected for multiple comparisons by false discovery rate (FDR).ResultAt baseline, CU old participants had lower CT values than CU young participants in the inferior parietal cortex and frontal and parietal regions. In comparison with CU old participants, MCI and AD showed widespread lower CT values, more pronounced in the medial temporal lobe (i.e., the entorhinal cortex and parahippocampal gyrus), inferior temporal cortex, medial prefrontal cortex, and medial parietal cortex (i.e., the posterior cingulate cortex and precuneus), with AD lower than MCI in these regions. These regions also showed the most longitudinal atrophy in both AD and MCI over 2 years. AD patients showed faster and more widespread atrophy patterns than MCI and CU old participants. We identified significant (PFDR<0.05) positive linear correlations between cognitive decline and regional CT measurements, particularly in regions showing significant cortical thinning across time.ConclusionIn this study, we replicated the typical cross‐sectional and longitudinal brain atrophy patterns, and relationships with cognitive decline in an Asian cohort. Our findings support the generalizability of atrophy patterns in MCI and AD, suggesting common neurobiological mechanisms underlying AD symptoms across different ethnoracial populations.