Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis

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.

Download Full-text

Nicotine Effects on White Matter Microstructure in Young Adults

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy101 ◽

2019 ◽

Vol 35 (1) ◽

pp. 10-21 ◽

Cited By ~ 2

Author(s):

Megan M Kangiser ◽

Alicia M Thomas ◽

Christine M Kaiver ◽

Krista M Lisdahl

Keyword(s):

Working Memory ◽

Young Adults ◽

White Matter ◽

Fractional Anisotropy ◽

Sustained Attention ◽

Verbal Memory ◽

Diffusion Tensor ◽

Memory Performance ◽

Mean Diffusivity ◽

White Matter Microstructure

Abstract Objective Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. Methods Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18–25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. Results Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus—temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. Conclusions Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

Download Full-text

Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging

Scientific Reports ◽

10.1038/s41598-021-90597-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shuang Ding ◽

Yu Guo ◽

Xiaoya Chen ◽

Silin Du ◽

Yongliang Han ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Mouse Model ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Blue Staining ◽

Resonance Imaging ◽

The Mean ◽

Underlying Mechanisms

AbstractThe aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Download Full-text

White matter network damage mediates association between cerebrovascular disease and cognition

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21990980 ◽

2021 ◽

pp. 0271678X2199098

Author(s):

Saima Hilal ◽

Siwei Liu ◽

Tien Yin Wong ◽

Henri Vrooman ◽

Ching-Yu Cheng ◽

...

Keyword(s):

White Matter ◽

Cerebrovascular Disease ◽

Verbal Memory ◽

Visual Memory ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Domain Specific ◽

Epidemiology Of Dementia ◽

Z Scores ◽

White Matter Connectivity

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.

Download Full-text

Verbal memory and hippocampal volume predict subsequent fornix microstructure in those at risk for Alzheimer’s disease

Brain Imaging and Behavior ◽

10.1007/s11682-019-00183-8 ◽

2019 ◽

Vol 14 (6) ◽

pp. 2311-2322 ◽

Cited By ~ 1

Author(s):

Junhong Yu ◽

◽

Tatia M. C. Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Verbal Memory ◽

Structural Equation ◽

Structural Equation Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Hippocampal Atrophy ◽

Cross Sectional ◽

Mci Due To Ad

Abstract While strong cross-sectional evidence supported the use of fornix microstructure as a marker for detecting Alzheimer’s disease (AD), longitudinal data remains inconclusive on the sequential nature of fornix microstructure abnormalities and AD progression. An unequivocal longitudinal relationship between fornix microstructure and markers of AD progression –memory impairment and hippocampal atrophy, must be established to validate fornix microstructure as a marker of AD progression. We included 115 participants from the Alzheimer’s Disease Neuroimaging Initiative across the non-demented AD spectrum— defined as those who had at least one AD risk marker at baseline (e.g., mild cognitive impairment (MCI) due to AD diagnosis, amyloid or ApoE4 positivity) and/or ‘cognitively normal individuals who converted to MCI due to AD or AD, with structural and diffusion tensor imaging scans at baseline and two years follow-up. Hippocampal volumes (HV), fractional anisotropy (FA) and mean diffusivity (MD) in the fornix were extracted. Memory was indexed via composite scores of verbal memory tests. Structural equation models tested the bidirectional cross-lagged effects of fornix microstructure, memory, and HV. Impaired memory and smaller HV at baseline significantly predicted worse fornix microstructure (decreased FA and increased MD) two years later. Baseline fornix microstructure was not associated with subsequent changes in memory and HV. Fornix microstructure is compromised likely at a later stage, where significant decline in memory and hippocampal atrophy have occurred. This limits the utility of fornix microstructure in the early detection of AD. Our findings inform the possible pathophysiology and refined the use of AD neural markers.

Download Full-text

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

Multiple Sclerosis Journal ◽

10.1191/1352458504ms997oa ◽

2004 ◽

Vol 10 (2) ◽

pp. 188-196 ◽

Cited By ~ 57

Author(s):

Emmanuelle Cassol ◽

Jean-Philippe Ranjeva ◽

Danielle Ibarrola ◽

Claude Mékies ◽

Claude Manelfe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Lesion Load ◽

Normal Appearing White Matter ◽

Relapsing Remitting ◽

One Year ◽

Diffusion Tensor Imaging Dti

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

Download Full-text

MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458503ms938oa ◽

2003 ◽

Vol 9 (6) ◽

pp. 554-565 ◽

Cited By ~ 40

Author(s):

J P Ranjeva ◽

J Pelletier ◽

S Confort-Gouny ◽

D Ibarrola ◽

B Audoin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Corpus Callosum ◽

Early Stage ◽

Magnetization Transfer ◽

Mean Diffusivity ◽

Clinically Isolated Syndrome ◽

Resonance Spectroscopy ◽

Magnetization Transfer Ratio ◽

R Ratio

A trophy of corpus callosum (C C) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of C C are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (C ISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure C C volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/C ho) ratio, N-acetyl aspartate/total creatine (NA A/C r) ratio and C ho/C r ratio inside the C C of 46 C ISSMS patients and 24 sexand age-matched controls. No atrophy of C C was observed in the C ISSMS group. C C of patients was character ized by decreased MTR and increased MD. No change in the NA A/C r ratio was observed while the NA A/C ho ratio decreased and C ho/C r ratio increased in the splenium and the central anterio r part of C C. These abnormalities were present in patients with, but also without, macroscopic lesions inside the C C. O ur results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin patho logy, occur in the C C at the earliest stage of MS before any atrophy is detected.

Download Full-text

Diffusion tensor imaging of the hippocampus and verbal memory performance: The RUN DMC Study

Human Brain Mapping ◽

10.1002/hbm.21231 ◽

2011 ◽

Vol 33 (3) ◽

pp. 542-551 ◽

Cited By ~ 30

Author(s):

Anouk G.W. van Norden ◽

Karlijn F. de Laat ◽

Ilma Fick ◽

Inge W.M. van Uden ◽

Lucas J.B. van Oudheusden ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Verbal Memory ◽

Diffusion Tensor ◽

Memory Performance

Download Full-text

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515596600 ◽

2015 ◽

Vol 22 (5) ◽

pp. 620-627 ◽

Cited By ~ 9

Author(s):

MA Rocca ◽

M Sonkin ◽

M Copetti ◽

E Pagani ◽

DL Arnold ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Structural Integrity ◽

Linear Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Lesion Volume ◽

Resonance Imaging ◽

The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

Download Full-text

Lifespan trajectories and relationships to memory of the macro- and microstructure of the anterior and posterior hippocampus – a longitudinal multi-modal imaging study

10.1101/564732 ◽

2019 ◽

Author(s):

Espen Langnes ◽

Markus H. Sneve ◽

Donatas Sederevicius ◽

Inge K. Amlien ◽

Kristine B Walhovd ◽

...

Keyword(s):

Episodic Memory ◽

Verbal Memory ◽

Structural Changes ◽

Diffusion Tensor ◽

Hippocampal Formation ◽

Memory Performance ◽

Memory Function ◽

Imaging Study ◽

Future Research ◽

Microstructural Development

AbstractThere is evidence for a hippocampal long axis anterior-posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance typically seen across development and aging. The hippocampal formation shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub-regions along the AP axis are not established. The aim of the present study was to test whether the micro- and macro-structural age-trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single-center longitudinal study, 1790 cognitively healthy participants, 4.1-93.4 years of age, underwent a total of 3367 MRI examinations and 3033 memory tests sessions over 1-6 time points, spanning an interval up to 11.1 years. T1-weighted scans were used to estimate the volume of aHC and pHC, and diffusion tensor imaging to measure mean diffusion (MD) within each region. We found that the macro- and microstructural lifespan-trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging-related changes. A similar aHC – pHC difference was observed for volume, although not as evident as for microstructure. All sub-regions showed age-dependent relationships to episodic memory function. For aHC micro- and macrostructure, the relationships to verbal memory performance varied significantly with age, being stronger among the older participants. Future research should disentangle the relationship between these structural properties and different memory processes – encoding vs. retrieval in particular – across the lifespan.

Download Full-text

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

Neurology Research International ◽

10.1155/2012/517876 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 19

Author(s):

F. Palesi ◽

P. Vitali ◽

P. Chiarati ◽

G. Castellazzi ◽

E. Caverzasi ◽

...

Keyword(s):

Verbal Memory ◽

Structural Damage ◽

Grey Matter ◽

Clinical Stage ◽

Mean Diffusivity ◽

Posterior Cingulate Cortex ◽

Hippocampal Damage ◽

Healthy Controls ◽

Alzheimers’S Disease ◽

Mr Volumetry

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.

Download Full-text