Dataset Information

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

ABSTRACT:

Background

There is growing interest in white matter (WM) imaging with positron emission tomography (PET).

Objectives

We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding.

Methods

In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences.

Results

MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS.

Conclusion

PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

SUBMITTER: Zeydan B

PROVIDER: S-EPMC5665724 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

Zeydan Burcu B Lowe Val J VJ Schwarz Christopher G CG Przybelski Scott A SA Tosakulwong Nirubol N Zuk Samantha M SM Senjem Matthew L ML Gunter Jeffrey L JL Roberts Rosebud O RO Mielke Michelle M MM Benarroch Eduardo E EE Rodriguez Moses M Machulda Mary M MM Lesnick Timothy G TG Knopman David S DS Petersen Ronald C RC Jack Clifford R CR Kantarci Kejal K Kantarci Orhun H OH

Multiple sclerosis (Houndmills, Basingstoke, England) 20170505 6

<h4>Background</h4>There is growing interest in white matter (WM) imaging with positron emission tomography (PET).<h4>Objectives</h4>We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding.<h4>Methods</h4>In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quanti ...[more]

PMID: 28474977

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Project description:During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our understanding of cognitive impairment in multiple sclerosis may increase substantially. Accordingly, this study aimed to investigate specific patterns of white matter degeneration, the evolution over time, the manifestation across different stages of the disease and their role in cognitive impairment using a novel fixel-based approach. Neuropsychological test scores and MRI scans including 30-direction diffusion-weighted images were collected from 327 multiple sclerosis patients (mean age = 48.34 years, 221 female) and 95 healthy controls (mean age = 45.70 years, 55 female). Of those, 233 patients and 61 healthy controls had similar follow-up assessments 5 years after. Patients scoring 1.5 or 2 standard deviations below healthy controls on at least two out of seven cognitive domains (from the Brief Repeatable Battery of Neuropsychological Tests, BRB-N) were classified as mildly cognitively impaired or cognitively impaired, respectively, or otherwise cognitively preserved. Fixel-based analysis of diffusion data was used to calculate fibre-specific measures (fibre density, reflecting microstructural diffuse axonal damage; fibre cross-section, reflecting macrostructural tract atrophy) within atlas-based white matter tracts at each visit. At baseline, all fixel-based measures were significantly worse in multiple sclerosis compared with healthy controls (P < 0.05). For both fibre density and fibre cross-section, a similar pattern was observed, with secondary progressive multiple sclerosis patients having the most severe damage, followed by primary progressive and relapsing-remitting multiple sclerosis. Similarly, damage was least severe in cognitively preserved (n = 177), more severe in mildly cognitively impaired (n = 63) and worst in cognitively impaired (n = 87; P < 0.05). Microstructural damage was most pronounced in the cingulum, while macrostructural alterations were most pronounced in the corticospinal tract, cingulum and superior longitudinal fasciculus. Over time, white matter alterations worsened most severely in progressive multiple sclerosis (P < 0.05), with white matter atrophy progression mainly seen in the corticospinal tract and microstructural axonal damage worsening in cingulum and superior longitudinal fasciculus. Cognitive decline at follow-up could be predicted by baseline fixel-based measures (R2 = 0.45, P < 0.001). Fixel-based approaches are sensitive to white matter degeneration patterns in multiple sclerosis and can have strong predictive value for cognitive impairment. Longitudinal deterioration was most marked in progressive multiple sclerosis, indicating that degeneration in white matter remains important to characterize further in this phenotype.

Dataset Information

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

Background

Objectives

Methods

Results

Conclusion

Publications

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

Similar Datasets

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