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Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis

Sarah Knowles, Rod Middleton Orcid Logo, Benjamin Cooze, Ildiko Farkas, Yeung Yeung Leung, Kelsey Allen, MOLLY WINSLADE, David R.J. Owen, Roberta Magliozzi Orcid Logo, Richard Reynolds, James W. Neal, Owen Pearson, Richard Nicholas Orcid Logo, Owen Pickrell Orcid Logo, Owain Howell Orcid Logo, (the UK MS Register Research Group)

Annals of Neurology, Volume: 95, Issue: 3, Pages: 471 - 486

Swansea University Authors: Sarah Knowles, Rod Middleton Orcid Logo, Benjamin Cooze, Kelsey Allen, MOLLY WINSLADE, Owen Pickrell Orcid Logo, Owain Howell Orcid Logo

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DOI (Published version): 10.1002/ana.26843

Abstract

Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?Methods: We used data from the UK MS Register to characterise demographics and clinica...

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Published in: Annals of Neurology
ISSN: 0364-5134 1531-8249
Published: Wiley 2024
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We performed a pathology study of a separate MS cohort with a later onset (n=18, mean age of onset 54 years) versus AOMS (n=23, age of onset 30 years).Results: In the Register cohort there were 1608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of females, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 v 28.3, p&lt;0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease modifying treatment and attained substantial disability sooner.Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whilst actively demyelinating lesions and compartmentalised inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalised inflammation, correlated with disability outcomes in older-onset MS.Interpretation: The more progressive nature of older-onset MS is associated with significant neurodegeneration but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people.</abstract><type>Journal Article</type><journal>Annals of Neurology</journal><volume>95</volume><journalNumber>3</journalNumber><paginationStart>471</paginationStart><paginationEnd>486</paginationEnd><publisher>Wiley</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0364-5134</issnPrint><issnElectronic>1531-8249</issnElectronic><keywords>Multiple Sclerosis, Disability</keywords><publishedDay>1</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2024</publishedYear><publishedDate>2024-03-01</publishedDate><doi>10.1002/ana.26843</doi><url>http://dx.doi.org/10.1002/ana.26843</url><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>Multiple Sclerosis Society HCRW BRAIN unit</funders><projectreference/><lastEdited>2024-07-15T11:57:46.8276989</lastEdited><Created>2023-12-20T11:00:39.5863712</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>Sarah</firstname><surname>Knowles</surname><order>1</order></author><author><firstname>Rod</firstname><surname>Middleton</surname><orcid>0000-0002-2130-4420</orcid><order>2</order></author><author><firstname>Benjamin</firstname><surname>Cooze</surname><order>3</order></author><author><firstname>Ildiko</firstname><surname>Farkas</surname><order>4</order></author><author><firstname>Yeung Yeung</firstname><surname>Leung</surname><order>5</order></author><author><firstname>Kelsey</firstname><surname>Allen</surname><order>6</order></author><author><firstname>MOLLY</firstname><surname>WINSLADE</surname><order>7</order></author><author><firstname>David R.J.</firstname><surname>Owen</surname><order>8</order></author><author><firstname>Roberta</firstname><surname>Magliozzi</surname><orcid>0000-0001-8284-7763</orcid><order>9</order></author><author><firstname>Richard</firstname><surname>Reynolds</surname><order>10</order></author><author><firstname>James W.</firstname><surname>Neal</surname><order>11</order></author><author><firstname>Owen</firstname><surname>Pearson</surname><order>12</order></author><author><firstname>Richard</firstname><surname>Nicholas</surname><orcid>0000-0003-0414-1225</orcid><order>13</order></author><author><firstname>Owen</firstname><surname>Pickrell</surname><orcid>0000-0003-4396-5657</orcid><order>14</order></author><author><firstname>Owain</firstname><surname>Howell</surname><orcid>0000-0003-2157-9157</orcid><order>15</order></author><author><firstname>(the UK MS Register Research</firstname><surname>Group)</surname><order>16</order></author></authors><documents><document><filename>65353__29807__3a76f17c371e4b28a7041542f135423e.pdf</filename><originalFilename>65353.VOR.pdf</originalFilename><uploaded>2024-03-22T16:55:44.5109011</uploaded><type>Output</type><contentLength>4504300</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>Distributed under a Creative Commons Attribution Non-Commercial 4.0 licence.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by-nc/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling v2 65353 2023-12-20 Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis 6c4c4acf0f27a0964f6f4b36c2a4ffac Sarah Knowles Sarah Knowles true false 005518f819ef1a2a13fdf438529bdfcd 0000-0002-2130-4420 Rod Middleton Rod Middleton true false 785346ffc3dae14c560e63727f4017d3 Benjamin Cooze Benjamin Cooze true false a57a44d79880dac72cd792a77a31851c Kelsey Allen Kelsey Allen true false 7bdc823654ce52cd446e9724f3617530 MOLLY WINSLADE MOLLY WINSLADE true false 1c3044b5ff7a6552ff5e8c9e3901c807 0000-0003-4396-5657 Owen Pickrell Owen Pickrell true false 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2023-12-20 MEDS Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?Methods: We used data from the UK MS Register to characterise demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared to adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n=18, mean age of onset 54 years) versus AOMS (n=23, age of onset 30 years).Results: In the Register cohort there were 1608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of females, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 v 28.3, p<0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease modifying treatment and attained substantial disability sooner.Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whilst actively demyelinating lesions and compartmentalised inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalised inflammation, correlated with disability outcomes in older-onset MS.Interpretation: The more progressive nature of older-onset MS is associated with significant neurodegeneration but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. Journal Article Annals of Neurology 95 3 471 486 Wiley 0364-5134 1531-8249 Multiple Sclerosis, Disability 1 3 2024 2024-03-01 10.1002/ana.26843 http://dx.doi.org/10.1002/ana.26843 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) Multiple Sclerosis Society HCRW BRAIN unit 2024-07-15T11:57:46.8276989 2023-12-20T11:00:39.5863712 Swansea University Medical School Medicine Sarah Knowles 1 Rod Middleton 0000-0002-2130-4420 2 Benjamin Cooze 3 Ildiko Farkas 4 Yeung Yeung Leung 5 Kelsey Allen 6 MOLLY WINSLADE 7 David R.J. Owen 8 Roberta Magliozzi 0000-0001-8284-7763 9 Richard Reynolds 10 James W. Neal 11 Owen Pearson 12 Richard Nicholas 0000-0003-0414-1225 13 Owen Pickrell 0000-0003-4396-5657 14 Owain Howell 0000-0003-2157-9157 15 (the UK MS Register Research Group) 16 65353__29807__3a76f17c371e4b28a7041542f135423e.pdf 65353.VOR.pdf 2024-03-22T16:55:44.5109011 Output 4504300 application/pdf Version of Record true Distributed under a Creative Commons Attribution Non-Commercial 4.0 licence. true eng http://creativecommons.org/licenses/by-nc/4.0/
title Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
spellingShingle Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
Sarah Knowles
Rod Middleton
Benjamin Cooze
Kelsey Allen
MOLLY WINSLADE
Owen Pickrell
Owain Howell
title_short Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
title_full Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
title_fullStr Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
title_full_unstemmed Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
title_sort Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older‐Onset Multiple Sclerosis
author_id_str_mv 6c4c4acf0f27a0964f6f4b36c2a4ffac
005518f819ef1a2a13fdf438529bdfcd
785346ffc3dae14c560e63727f4017d3
a57a44d79880dac72cd792a77a31851c
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author_id_fullname_str_mv 6c4c4acf0f27a0964f6f4b36c2a4ffac_***_Sarah Knowles
005518f819ef1a2a13fdf438529bdfcd_***_Rod Middleton
785346ffc3dae14c560e63727f4017d3_***_Benjamin Cooze
a57a44d79880dac72cd792a77a31851c_***_Kelsey Allen
7bdc823654ce52cd446e9724f3617530_***_MOLLY WINSLADE
1c3044b5ff7a6552ff5e8c9e3901c807_***_Owen Pickrell
58c995486fc93a242b987640b692db8c_***_Owain Howell
author Sarah Knowles
Rod Middleton
Benjamin Cooze
Kelsey Allen
MOLLY WINSLADE
Owen Pickrell
Owain Howell
author2 Sarah Knowles
Rod Middleton
Benjamin Cooze
Ildiko Farkas
Yeung Yeung Leung
Kelsey Allen
MOLLY WINSLADE
David R.J. Owen
Roberta Magliozzi
Richard Reynolds
James W. Neal
Owen Pearson
Richard Nicholas
Owen Pickrell
Owain Howell
(the UK MS Register Research Group)
format Journal article
container_title Annals of Neurology
container_volume 95
container_issue 3
container_start_page 471
publishDate 2024
institution Swansea University
issn 0364-5134
1531-8249
doi_str_mv 10.1002/ana.26843
publisher Wiley
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
url http://dx.doi.org/10.1002/ana.26843
document_store_str 1
active_str 0
description Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?Methods: We used data from the UK MS Register to characterise demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared to adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n=18, mean age of onset 54 years) versus AOMS (n=23, age of onset 30 years).Results: In the Register cohort there were 1608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of females, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 v 28.3, p<0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease modifying treatment and attained substantial disability sooner.Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whilst actively demyelinating lesions and compartmentalised inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalised inflammation, correlated with disability outcomes in older-onset MS.Interpretation: The more progressive nature of older-onset MS is associated with significant neurodegeneration but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people.
published_date 2024-03-01T11:57:46Z
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