Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease.

INTRODUCTION: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH-connected cortex using multimodal images. METHODS: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aß) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography. RESULTS: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aß and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18F-SynVesT-1 PET. In addition, higher ratios of Aß in the deep WMH-connected versus WMH-unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH-connected cortex reduced more than WMH-unconnected cortex over 12 months. DISCUSSION: Our results suggest that WMH may be associated with AD-intrinsic processes of degeneration, in addition to vascular mechanisms. HIGHLIGHTS: We studied white matter hyperintensities (WMHs) and WMH-connected cortical changes. WMHs are associated with more severe regional cortical degeneration. Findings suggest WMHs may be associated with Alzheimer's disease-intrinsic processes of degeneration.

The hippocampus as a structural and functional network epicentre for distant cortical thinning in neurocognitive aging.

Alterations in grey matter (GM) and white matter (WM) are associated with memory impairment across the neurocognitive aging spectrum and theorised to spread throughout brain networks. Functional and structural connectivity (FC,SC) may explain widespread atrophy. We tested the effect of SC and FC to the hippocampus on cortical thickness (CT) of connected areas. In 419 (223 F) participants (agemean=73 ±â€¯8) from the Alzheimer's Disease Neuroimaging Initiative, cortical regions associated with memory (Rey Auditory Verbal Learning Test) were identified using Lasso regression. Two structural equation models (SEM), for SC and resting-state FC, were fitted including CT areas, and SC and FC to the left and right hippocampus (LHIP,RHIP). LHIP (ß=-0.150,p=<.001) and RHIP (ß=-0.139,p=<.001) SC predicted left temporopolar/rhinal CT; RHIP SC predicted right temporopolar/rhinal CT (ß=-0.191,p=<.001). LHIP SC predicted right fusiform/parahippocampal (ß=-0.104,p=.011) and intraparietal sulcus/superior parietal CT (ß=0.101,p=.028). Increased RHIP FC predicted higher left inferior parietal CT (ß=0.132,p=.042) while increased LHIP FC predicted lower right fusiform/parahippocampal CT (ß=-0.97; p=.023). The hippocampi may be epicentres for cortical thinning through disrupted connectivity.

Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with ß-amyloid status in cognitively normal adults at age 70.

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.

Association of Neighborhood Context, Cognitive Decline, and Cortical Change in an Unimpaired Cohort.

OBJECTIVE: To test the hypothesis that neighborhood-level disadvantage is associated with longitudinal measures of neurodegeneration and cognitive decline in an unimpaired cohort. METHODS: Longitudinal MRI and cognitive testing data were collected from 601 cognitively unimpaired participants in the Wisconsin Registry for Alzheimer's Prevention Study and the Wisconsin Alzheimer's Disease Research Center clinical cohort. Area Deprivation Index was geospatially determined based on participant residence geocode and ranked relative to state of residence. Linear regression models were fitted to test associations between neighborhood-level disadvantage and longitudinal change in cortical thickness and cognitive test performance. Mediation tests were used to assess whether neurodegeneration and cognitive decline were associated with neighborhood-level disadvantage along the same theoretical causal path. RESULTS: In our middle- to older-aged study population (mean baseline age 59 years), living in the 20% most disadvantaged neighborhoods (n = 19) relative to state of residence was associated with cortical thinning in Alzheimer signature regions (p = 0.002) and decline in the Preclinical Alzheimer's Disease Cognitive Composite (p = 0.04), particularly the Trail-Making Test, part B (p < 0.001), but not Rey Auditory Verbal Learning Test (p = 0.77) or Story Memory Delayed Recall (p = 0.49) subtests. Associations were attenuated but remained significant after controlling for racial and demographic differences between neighborhood-level disadvantage groups. Cortical thinning partially mediated the association between neighborhood-level disadvantage and cognitive decline. CONCLUSIONS: In this longitudinal study of cognitively unimpaired adults, living in the most highly disadvantaged neighborhoods was associated with accelerated degeneration in Alzheimer signature regions and cognitive decline. This study provides further evidence for neighborhood-level disadvantage as a risk factor for preclinical neurodegeneration and cognitive decline in certain populations. Limitations of the present study, including a small number of participants from highly disadvantaged neighborhoods and a circumscribed geographic setting, should be explored in larger and more diverse study cohorts.

Clinical and Biological Correlates of White Matter Hyperintensities in Patients With Behavioral-Variant Frontotemporal Dementia and Alzheimer Disease.

OBJECTIVE: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses. METHODS: A total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy, and performance across different cognitive domains were assessed. RESULTS: Total WMH volumes were larger in patients with bvFTD than patients with AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. Patients with bvFTD and patients with AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD. CONCLUSION: Increased WMH are common in patients with bvFTD and patients with AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Furthermore, increased WMH in different regions contributes to cognitive deficits.

Pattern of cortical thinning in logopenic progressive aphasia patients in Thailand.

BACKGROUND: Logopenic progressive aphasia (LPA) is an uncommon neurodegenerative disorder primarily characterized by word-finding difficulties and sentence repetition impairment. Prominent cortical atrophy around left temporo-parietal junction (TPJ) is a classical imaging feature of LPA. This study investigated cortical thinning pattern in clinically diagnosed LPA patients using non-demented subjects as a control group. We also aimed to explore whether there was prominent thinning of other cortical area additional to the well-recognized left TPJ. METHODS: Thicknesses of all cortical regions were measured from brain magnetic resonance images using an automated command on Freesurfer software. Cortical thickness of the LPA and control groups were compared by two methods: 1) using a general linear model (GLM) in SPSS software; and 2) using a vertex-by-vertex GLM, performed with Freesurfer's QDEC interface. RESULTS: Besides the well-recognized left TPJ, cortical regions that were significantly thinner in the LPA group by both comparison methods included left caudal middle frontal gyrus (CMFG) (p = 0.006 by SPSS, p = 0.0003 by QDEC), left rostral middle frontal gyrus (p = 0.001 by SPSS, p = 0.0001 by QDEC), left parahippocampal gyrus (p = 0.008 by SPSS, p = 0.005 by QDEC) and right CMFG (p = 0.005 by SPSS, p = 0.0001 by QDEC). CONCLUSIONS: Our results demonstrated that thinning of middle frontal gyri may be an additional feature in clinically diagnosed LPA patients. Involvement of left parahippocampal gyrus may reflect the underlying neuropathology of Alzheimer's disease in majority of the LPA patients.

Cortical thickness in Parkinson's disease: a coordinate-based meta-analysis.

Parkinson's disease (PD) is a common age-related neurodegenerative disease that affects the structural architecture of the cerebral cortex. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis is a popular measure to assess brain structural alterations in the gray matter in PD. However, the results of CTh analysis in PD lack consistency and have not been systematically reviewed. We conducted a comprehensive coordinate-based meta-analysis (CBMA) of 38 CTh studies (57 comparison datasets) in 1,843 patients with PD using the latest seed-based d mapping software. Compared with 1,172 healthy controls, no significantly consistent CTh alterations were found in patients with PD, suggesting CTh as an unreliable neuroimaging marker for PD. The lack of consistent CTh alterations in PD could be ascribed to the heterogeneity in clinical populations, variations in imaging methods, and underpowered small sample sizes. These results highlight the need to control for potential confounding factors to produce robust and reproducible CTh results in PD.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Cellular correlates of cortical thinning throughout the lifespan.

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer's Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

Resective surgery prevents progressive cortical thinning in temporal lobe epilepsy.

Focal epilepsy in adults is associated with progressive atrophy of the cortex at a rate more than double that of normal ageing. We aimed to determine whether successful epilepsy surgery interrupts progressive cortical thinning. In this longitudinal case-control neuroimaging study, we included subjects with unilateral temporal lobe epilepsy (TLE) before (n = 29) or after (n = 56) anterior temporal lobe resection and healthy volunteers (n = 124) comparable regarding age and sex. We measured cortical thickness on paired structural MRI scans in all participants and compared progressive thinning between groups using linear mixed effects models. Compared to ageing-related cortical thinning in healthy subjects, we found progressive cortical atrophy on vertex-wise analysis in TLE before surgery that was bilateral and localized beyond the ipsilateral temporal lobe. In these regions, we observed accelerated annualized thinning in left (left TLE 0.0192 ± 0.0014 versus healthy volunteers 0.0032 ± 0.0013 mm/year, P < 0.0001) and right (right TLE 0.0198 ± 0.0016 versus healthy volunteers 0.0037 ± 0.0016 mm/year, P < 0.0001) presurgical TLE cases. Cortical thinning in these areas was reduced after surgical resection of the left (0.0074 ± 0.0016 mm/year, P = 0.0006) or right (0.0052 ± 0.0020 mm/year, P = 0.0006) anterior temporal lobe. Directly comparing the post- versus presurgical TLE groups on vertex-wise analysis, the areas of postoperatively reduced thinning were in both hemispheres, particularly, but not exclusively, in regions that were affected preoperatively. Participants who remained completely seizure-free after surgery had no more progressive thinning than that observed during normal ageing. Those with postoperative seizures had small areas of continued accelerated thinning after surgery. Thus, successful epilepsy surgery prevents progressive cortical atrophy that is observed in TLE and may be potentially neuroprotective. This effect was more pronounced in those who remained seizure-free after temporal lobe resection, normalizing the rate of atrophy to that of normal ageing. These results provide evidence of epilepsy surgery preventing further cerebral damage and provide incentives for offering early surgery in refractory TLE.

Not Just for Joints: The Associations of Moderate-to-Vigorous Physical Activity and Sedentary Behavior with Brain Cortical Thickness.

INTRODUCTION: Cortical thinning is associated with aging; however, lifestyle factors can moderate this relationship. Two distinct lifestyle behaviors associated with brain health are regular moderate-to-vigorous physical activity (MVPA) and limited sedentary behavior (SB). However, it is unclear whether MVPA and SB levels contribute to cortical thickness independent of each other. We therefore investigated the independent relationships of MVPA and SB with cortical thickness using baseline data from a randomized controlled trial. METHODS: At baseline, we measured MVPA and SB for 7 d using the SenseWear Mini. A subset of the randomized controlled trial participants (n = 30) underwent a 3T magnetic resonance imaging scan, wherein region-specific cortical surface morphometric analyses were performed using T1-weighted structural magnetic resonance imaging. We conducted regression analyses using a surface-based cluster size exclusion method for multiple comparisons within FreeSurfer neuroimaging software to determine if MVPA and SB are independently correlated with region-specific cortical thickness. RESULTS: This subset of participants had a mean age of 61 yr (SD = 9 yr), and 80% were female. Higher MVPA was associated with greater cortical thickness in the temporal pole (cluster size, 855 mm; cortical thickness range, 2.59-3.72 mm; P < 0.05) and superior frontal gyrus (cluster size, 1204 mm; cortical thickness range, 2.41-3.15 mm; P < 0.05) of the left hemisphere, independent of SB. Sedentary behavior was not associated with greater cortical thickness in any region, independent of MVPA. CONCLUSIONS: Our results indicate that adults with greater MVPA-independent of SB-are associated with greater cortical thickness in regions, which are susceptible to age-associated atrophy.

Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

BACKGROUND: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. DESIGN: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI). RESULTS: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy. CONCLUSIONS AND RELEVANCE: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Inferior temporal tau is associated with accelerated prospective cortical thinning in clinically normal older adults.

Neurofibrillary tau tangles are a hallmark pathology of Alzheimer's disease (AD) and are more closely associated with AD-related cortical atrophy and symptom severity than amyloid-beta (Aß). However, studies regarding the effect of tau on longitudinal cortical thinning, particularly in healthy aging and preclinical AD, have been limited in number due to the relatively recent introduction of in vivo PET tracers for imaging tau pathology. Here, we investigate [18F]-flortaucipir (FTP, a marker of paired helical filament tau) PET as a predictor of atrophy in healthy aging and preclinical AD. We examine longitudinal structural MRI brain imaging data, retrospectively and prospectively relative to FTP imaging, using piecewise linear mixed-effect models with time centered at each participant's FTP-PET session. Participants include 111 individuals from the Harvard Aging Brain Study who underwent at least three MRI sessions over an average of 4.46 years and one FTP-PET at the approximate midpoint of the observation period. Our primary analyses focus on inferior temporal (IT) FTP standardized uptake value ratios and longitudinal FreeSurfer defined cortical regions of interest. Relationships were also explored using other regional FTP measures (entorhinal, composite, and local), within high and low Pittsburgh compound-B (PiB) PET groups, and with longitudinal subcortical volume. Strong associations between IT FTP and cortical thinning were found, most notably in temporal, midline, and prefrontal regions, with stronger effects generally observed in the prospective as compared to retrospective time frame. Significant differences between prospective and retrospective rates of thinning were found in the inferior and middle temporal gyri, cingulate areas, as well as pars orbitalis such that higher IT FTP was associated with greater prospective rates of thinning. Within the high PiB group, significant differences between prospective and retrospective rates of thinning were similarly observed. However, no consistent pattern of tau-related change in cortical thickness within the low PiB group was discerned. These results provide support for the hypothesis that tau pathology is a driver of future atrophy as well as provide additional evidence for tau-PET as an effective AD biomarker for interventional clinical trials.

Impacts of Kidney Dysfunction and Cerebral Cortical Thinning on Cognitive Change in Elderly Population.

BACKGROUND: Cerebral cortical thickness is a neuroimaging biomarker to predict cognitive decline, and kidney dysfunction (KD) is associated with cortical thinning. OBJECTIVE: This study aimed to investigate the effects of KD and cortical thinning on cognitive change in a prospective cohort study. METHODS: A total of 244 non-demented participants were recruited from elderly health checkup program and received cognitive exams including Montreal Cognitive Assessment (MoCA) and different cognitive domains at baseline and three biannual follow-ups afterwards. KD was defined as having either glomerular filtration rate <60 ml/min/1.73 m2 or proteinuria. Cortical thickness of global, lobar, and Alzheimer's disease (AD) signature area were derived from magnetic resonance imaging at baseline, and cortical thinning was defined as the lowest tertile of cortical thickness. Generalized linear mixed models were applied to evaluate the effects of KD and cortical thinning on cognitive changes. RESULTS: KD was significantly associated with the decline in attention function (ß= -0.29). Thinning of global (ß= -0.06), AD signature area (ß= -0.06), temporal (ß= -0.06), and parietal lobes (ß= -0.06) predicted poor verbal fluency over time, while temporal lobe thinning also predicted poor MoCA score (ß= -0.19). KD modified the relationship between thinning of global, frontal, and limbic, and change of logical memory function (pinteraction < 0.05). When considering jointly, participants with both KD and cortical thinning had greatest decline in attention function compared with those without KD or cortical thinning (ß= -0.51, ptrend = 0.008). CONCLUSIONS: KD and cortical thinning have joint effect on cognitive decline, especially the attention function. Reverse associations may exist between cortical thinning and memory function in participants with KD, though the results should be interpreted cautiously as an exploratory analysis.

Medical Conditions Linked to Atherosclerosis Are Associated With Magnified Cortical Thinning in Individuals With Alcohol Use Disorders.

AIMS: Magnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion. METHODS: Treatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic-) and CON were compared on regional cortical thickness. RESULTS: Individuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic- had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic- in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions. CONCLUSIONS: Our results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.

Evidence of regional associations between age-related inter-individual differences in resting-state functional connectivity and cortical thinning revealed through a multi-level analysis.

Normal aging incurs functional and anatomical alterations in the brain. Cortical thinning, age-related alterations in resting-state functional connectivity (RSFC) and reductions in fractional amplitude of low frequency fluctuations (fALFF) are key components of brain aging that can be studied by neuroimaging. However, the level of association between these processes has not been fully established. We performed an analysis at multiple-levels, i.e. region or connection and modality, to investigate whether the evidence for the effect of aging on fALFF, RSFC and cortical thickness are associated in a large cohort. Our results show that there is a positive association between the level of evidence of age-related effects in all three in the brain. We also demonstrate that on a regional basis the association between RSFC alterations and cortical atrophy may be either positive or negative, which may relate to compensatory mechanisms predicted by the Scaffolding Theory of Aging and Cognition (STAC).

Longitudinal patterns of cortical thinning in multiple sclerosis.

In multiple sclerosis (MS), cortical atrophy is correlated with clinical and neuropsychological measures. We aimed to examine the differences in the temporospatial evolution of cortical thickness (CTh) between MS-subtypes and to study the association of CTh with T2-weighted white matter lesions (T2LV) and clinical progression. Two hundred and forty-three MS patients (180 relapsing-remitting [RRMS], 51 secondary-progressive [SPMS], and 12 primary-progressive [PPMS]) underwent annual clinical (incl. expanded disability status scale [EDSS]) and MRI-examinations over 6 years. T2LV and CTh were measured. CTh did not differ between MS-subgroups. Higher total T2LV was associated with extended bilateral CTh-reduction on average, but did not correlate with CTh-changes over time. In RRMS, CTh- and EDSS-changes over time were negatively correlated in large bilateral prefrontal, frontal, parietal, temporal, and occipital areas. In SPMS, CTh was not associated with the EDSS. In PPMS, CTh- and EDSS-changes over time were correlated in small clusters predominantly in left parietal areas. Increase of brain lesion load does not lead to an immediate CTh-reduction. Although CTh did not differ between MS-subtypes, a dissociation in the correlation between CTh- and EDSS-changes over time between RRMS and progressive-MS was shown, possibly underlining the contribution of subcortical pathology to clinical progression in progressive-MS.

Low CD4 nadir linked to widespread cortical thinning in adults living with HIV.

BACKGROUND: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. METHODS: High resolution structural MRI images and neuropsychological data were obtained from fifty-nine HIV+ adults (mean age, 56.5 ± 5.8) to investigate the correlation between CD4 nadir and cortical thickness. RESULTS: Low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions, and global mean cortical thickness correlated with CD4 nadir. In addition, worse global neurocognitive function was associated with bilateral frontal cortical thinning, and the association largely persisted (especially in the left frontal cortex) in the subset of participants who did not meet HAND criteria. CONCLUSIONS: These results suggest that low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. The diffuse neural injury might contribute to the prevalence and the phenotypes of HAND, as well as the difficulty treating HAND due to a broad network of brain regions affected. Low CD4 nadir related neural injury to the frontal cortex might contribute to subtle neurocognitive impairment/decline, even in the absence of HAND diagnosis.

An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium.

BACKGROUND: Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample. METHOD: To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls. RESULTS: The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression. CONCLUSION: These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.