scholarly journals DTI and MR Volumetry of Hippocampus-PC/PCC Circuit: In Search of Early Micro- and Macrostructural Signs of Alzheimers's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
F. Palesi ◽  
P. Vitali ◽  
P. Chiarati ◽  
G. Castellazzi ◽  
E. Caverzasi ◽  
...  

Hippocampal damage, by DTI or MR volumetry, and PET hypoperfusion of precuneus/posterior cingulate cortex (PC/PCC) were proposed as biomarkers of conversion from preclinical (MCI) to clinical stage of Alzheimer's disease (AD). This study evaluated structural damage, by DTI and MR volumetry, of hippocampi and tracts connecting hippocampus to PC/PCC (hipp-PC/PCC) in 10 AD, 10 MCI, and 18 healthy controls (CTRL). Normalized volumes, mean diffusivity (MD), and fractional anisotropy (FA) were obtained for grey matter (GM), white matter (WM), hippocampi, PC/PCC, and hipp-PC/PCC tracts. In hippocampi and hipp-PC/PCC tracts, decreased volumes and increased MD were found in AD versus CTRL (P<.001). The same results with lower significance (P<.05) were found in MCI versus CTRL. Verbal memory correlated (P<.05) in AD with left hippocampal and hipp-PC/PCC tract MD, and in MCI with FA of total WM. Both DTI and MR volumetry of hippocampi and hipp-PC/PCC tracts detect early signs of AD in MCI patients.

2016 ◽  
Vol 23 (9) ◽  
pp. 1214-1224 ◽  
Author(s):  
Vincent Planche ◽  
Aurélie Ruet ◽  
Pierrick Coupé ◽  
Delphine Lamargue-Hamel ◽  
Mathilde Deloire ◽  
...  

Objective: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load. Results: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls. Decrease in hippocampal FA together with increased mean diffusivity (MD) was even more prominent in MS patients. In CIS, hippocampal MD was correlated with episodic verbal memory performance ( r = −0.57, p = 0.0002 and odds ratio (OR) = 0.058, 95% confidence interval (CI) = 0.0057–0.59, p = 0.016 adjusted for age, gender, depression and T2-lesion load), but not with cognitive tasks unrelated to hippocampal functions. Hippocampal MD was the only variable discriminating memory-impaired from memory-preserved persons with CIS (area under the curve (AUC) = 0.77, sensitivity = 90.0%, specificity = 70.3%, positive predictive value (PPV) = 52.9%, negative predictive value (NPV) = 95.0%). Conclusion: DTI alterations within the hippocampus might reflect early neurodegenerative processes that are correlated with episodic memory performance, discriminating persons with CIS according to their memory status.


2017 ◽  
Author(s):  
Arman Eshaghi ◽  
Razvan V. Marinescu ◽  
Alexandra L. Young ◽  
Nicholas C. Firth ◽  
Ferran Prados ◽  
...  

SummaryGrey matter atrophy is present from the earliest clinical stages of multiple sclerosis (MS), but the temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in MS, and its association with disability accumulation.In this longitudinal study, we included 1,417 subjects: 253 with clinically-isolated syndrome (CIS), 708 relapsing-remitting MS (RRMS), 128 secondary-progressive MS (SPMS), 125 primary-progressive MS (PPMS), and 203 healthy controls from 7 European centres. Subjects underwent repeated MRI scanning (total number of scans 3,604); the mean follow-up for patients was 2.41yrs (SD±1.97). Disability was scored using the Expanded Disability Status Scale (EDSS). We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template. We used an established data-driven event-based model (EBM) to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific EBM stage, based on the number of their atrophic regions. We used nested linear mixed-effects regression models to explore the associations between the rate of increase in the EBM stages over time, disease duration and annual rate of EDSS gain.The first regions to become atrophic in CIS and relapse-onset MS patients (RRMS and SPMS) were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. The sequence of atrophy in PPMS showed a similar involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset MS and late atrophy in PPMS. Patients with SPMS showed the highest EBM stages (highest number of atrophic regions, all p<0.001) at study entry. Rates of increase in EBM stages were significantly different from healthy controls in all MS phenotypes, except for CIS. The increase in the number of atrophic regions (EBM stage) was associated with disease duration in all patients. EBM stage was associated with disability accumulation in RRMS independent of disease duration (p<0.0001).This data-driven staging of atrophy progression in a large MS sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across MS phenotypes. The spread of atrophy was associated with disease duration, and disability accumulation in RRMS.AbbreviationsMSmultiple sclerosisGMgrey matterFLAIRFluid Attenuated Inversion RecoveryPPMSprimary progressive multiple sclerosis; primary-progressive MS


2017 ◽  
Vol 89 (5) ◽  
pp. 518-525 ◽  
Author(s):  
Owen Robert Phillips ◽  
Shantanu H Joshi ◽  
Katherine L Narr ◽  
David W Shattuck ◽  
Manpreet Singh ◽  
...  

BackgroundClinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.MethodsForty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.ResultsNon-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.ConclusionsAnti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.


2017 ◽  
Vol 7 (20;7) ◽  
pp. E1025-E1051
Author(s):  
Iris Coppieters

Background: Patients with chronic whiplash-associated disorders (CWAD) are characterized by pain of traumatic origin, cognitive deficits, and central sensitization (CS). Previous neuroimaging studies revealed altered grey matter volume (GMV) in mild traumatic brain injury patients and chronic pain conditions also characterized by CS. It can therefore be hypothesized that GMV alterations also play a role in the persistent complaints of CWAD. However, brain alterations remain poorly investigated in these patients. Objectives: This study examined regional GMV alterations in patients with CWAD compared to patients with non-traumatic chronic idiopathic neck pain (CINP), who normally do not show CS at a group level, and healthy controls. Additionally, in both patient groups, relationships between regional GMV and measures of cognition as well as pain processing were assessed. Study Design: A cross-sectional case-control study. Setting: This study was performed at the Department of Rehabilitation Sciences and Physiotherapy of Ghent University in cooperation with the Ghent Institute for Functional and Metabolic Imaging. Methods: Ninety-three women (28 healthy controls, 34 CINP patients, and 31 CWAD patients) were enrolled. First, T1-weighted magnetic resonance images (MRIs) were acquired to examine GMV alterations in the brain regions involved in processing cognition and pain. Next, cognitive performance, pain cognitions, and CS symptoms were assessed. Finally, hyperalgesia and conditioned pain modulation efficacy were examined. Results: Regional GMV of the right lateral orbitofrontal cortex, left supramarginal cortex, and left posterior cingulate cortex was decreased in CWAD patients compared to healthy controls (P = 0.023; P = 0.012; P = 0.047, respectively). Additionally, GMV of the right superior parietal cortex and left posterior cingulate cortex was decreased in CWAD patients compared to CINP patients (P = 0.008; P = 0.035, respectively). Decreased regional GMV correlated with worse cognitive performance, higher maladapted pain cognitions, CS symptoms, and hyperalgesia in CWAD patients (rs = -0.515 to -0.657; P < 0.01). In CINP patients, decreased regional GMV correlated only with worse cognitive performance (rs = -0.499 to -0.619; P < 0.01), and no GMV differences compared with the controls could be revealed. Limitations: No conclusions about the causality of the observed relationships can be drawn. Conclusions: These results provide the first evidence for reduced GMV in cortical regions involved in processing cognition and pain in patients with CWAD. Accordingly, it is recommended that therapy approaches for CWAD patients should address the brain and take into account neuroplasticity of the central nervous system (CNS). Key words: Whiplash injuries, neck pain, magnetic resonance imaging, grey matter, cognitive dysfunction, pain catastrophizing, central sensitization


2021 ◽  
pp. jnnp-2020-323541
Author(s):  
Jessica L Panman ◽  
Vikram Venkatraghavan ◽  
Emma L van der Ende ◽  
Rebecca M E Steketee ◽  
Lize C Jiskoot ◽  
...  

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.


2021 ◽  
pp. 0271678X2199098
Author(s):  
Saima Hilal ◽  
Siwei Liu ◽  
Tien Yin Wong ◽  
Henri Vrooman ◽  
Ching-Yu Cheng ◽  
...  

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang Wen ◽  
Junjuan Yan ◽  
Liping Yu ◽  
Fang Wang ◽  
Jingran Liu ◽  
...  

Abstract Background Tourette syndrome (TS) is a neurodevelopmental disorder defined by the continual presence of primary motor and vocal tics. Grey matter abnormalities have been identified in numerous studies of TS, but conflicting results have been reported. This study was an unbiased statistical meta-analysis of published neuroimaging studies of TS structures. Methods A voxel quantitative meta-analysis technique called activation likelihood estimation (ALE) was used. The meta-analysis included six neuroimaging studies involving 247 TS patients and 236 healthy controls. A statistical threshold of p < 0.05 was established based on the false discovery rate and a cluster extent threshold of 50 voxels. Results We found that grey matter volumes were significantly increased in the bilateral thalamus, right hypothalamus, right precentral gyrus, left postcentral gyrus, left inferior parietal lobule, right lentiform nucleus, and left insula of TS patients compared to those of healthy controls. In contrast, grey matter volumes were significantly decreased in the bilateral postcentral gyrus, bilateral anterior cingulate, bilateral insula, left posterior cingulate and left postcentral gyrus of TS patients compared to those of healthy controls. Conclusions Our present meta-analysis primarily revealed significant increases in grey matter volumes in the thalamus and lentiform nucleus, and decreased grey matter volumes in the anterior cingulate gyrus, of TS patients compared to those in healthy controls. Most of these identified regions are associated with cortico-striato-thalamo-cortical circuits. Further studies with larger sample sizes are needed to confirm these changes in grey matter volumes in TS patients.


2017 ◽  
Vol 24 (3) ◽  
pp. 354-357 ◽  
Author(s):  
Lisa F Barcellos ◽  
Kalliope H Bellesis ◽  
Ling Shen ◽  
Xiaorong Shao ◽  
Terrence Chinn ◽  
...  

We used the California Verbal Learning Test, Second Edition (CVLT-II), one component of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), to determine feasibility of a remote assessment protocol. We compared telephone-administered CVLT-II data from MS patients to data acquired in person from an independent sample of patients and healthy controls. Mixed factor analyses of variance (ANOVAs) showed no significant differences between patient groups, but between-group effects comparing patients and healthy controls were significant. In this study, CVLT-II assessment by conventional in-person and remote telephone assessment yielded indistinguishable results. The findings indicate that telephone-administered CVLT-II is feasible. Further validation studies are underway.


2020 ◽  
Author(s):  
Elizabeth Race ◽  
Camille Carlisle ◽  
Ruchi Tejwani ◽  
Mieke Verfaellie

AbstractAccumulating evidence suggests that the hippocampus plays a critical role in the creative and flexible use of language. For example, amnesic patients with hippocampal damage produce less coherent and cohesive verbal discourse when constructing narratives about the past, present, and future. A recent study by Hilverman and colleagues (2017) found that amnesic patients with hippocampal damage also use less imageable words during narrative construction compared to healthy controls. These results suggest that in addition to supporting language use at the discourse level, the hippocampus also influences the quality of language at the single word level. However, the generalizability of these results to different types of language production tasks and the relationship to patients’ broader impairments in episodic memory have yet to be examined. In the current study, we investigated whether amnesic patients with hippocampal damage produce less imageable words compared to healthy controls in two different types of language production tasks. In Experiment 1, participants constructed narratives about events depicted in visually presented pictures (picture narratives). In Experiment 2, participants constructed verbal narratives about remembered events from the past or simulated events in the future (past/future narratives). Across all types of narratives, patients produced words that were rated as having similar levels of imageability compared to controls. Importantly, this was the case both in patients’ picture narratives, which did not require generating details from long-term memory and were matched to controls’ with respect to narrative content, and in patients’ narratives about past/future events, which required generating details from long-term memory and which were reduced in narrative content compared to those of controls. These results reveal that the hippocampus is not necessary for the use of imageable representations at the linguistic level, and that hippocampal contributions to imageable word use are independent of hippocampal contributions to episodic memory.


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