Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression
Background: Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge. Objective: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods: Using data from the Parki...
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| Veröffentlicht in: | Journal of Parkinson's disease 2023-01, Vol.13 (6), p.899-916 |
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| creator | Brumm, Michael C. Siderowf, Andrew Simuni, Tanya Burghardt, Elliot Choi, Seung Ho Caspell-Garcia, Chelsea Chahine, Lana M. Mollenhauer, Brit Foroud, Tatiana Galasko, Douglas Merchant, Kalpana Arnedo, Vanessa Hutten, Samantha J. O’Grady, Alyssa N. Poston, Kathleen L. Tanner, Caroline M. Weintraub, Daniel Kieburtz, Karl Marek, Kenneth Coffey, Christopher S. |
| description | Background:
Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.
Objective:
To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.
Methods:
Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.
Results:
Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p |
| doi_str_mv | 10.3233/JPD-223433 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10578214</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.3233_JPD-223433</sage_id><sourcerecordid>2862578328</sourcerecordid><originalsourceid>FETCH-LOGICAL-c439t-89f5b853d948a274b73073549b862ff4e4eeccd83fdf383d9a017a67d5b86d4b3</originalsourceid><addsrcrecordid>eNptkd9KwzAUxoMobqg3PoAEvBCEatOkTeaNzP_KhgMVvAtpm9bobDRpB7vzNXw9n8QjnXMDz00OnN_5zhc-hLZJeEAjSg9vRmdBFFFG6QrqEsF5wIl4XJ33nHTQlvfPIVRMEthZRx3KWSxClnRRM1LuxVTeVl8fnx6PnC2d9t7YCg9hop3H15WpjarNRB_hPh6asfa1rXRworzO8V3tVK3LKa4tHlpArcPLmmfGa0AXtTfRWqHGXm_N3g30cHF-f3oVDG4vr0_7gyBjtFcHolfEqYhp3mNCRZylnIacxqyXiiQqCqaZ1lmWC1rkBRWAqZBwlfActpKcpXQDHbe6b036qvNMV-B2LN-ceVVuKq0ycnlSmSdZ2okkYcxFRBgo7M4UnH1v4Ofy2TauAtMyAhNA0UgAtd9SmbPeO13MT5BQ_sQkISbZxgTwzqKpOfobCgB7LeBVqf_u_SP1Dcy8na8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2862578328</pqid></control><display><type>article</type><title>Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression</title><source>DOAJ Directory of Open Access Journals</source><creator>Brumm, Michael C. ; Siderowf, Andrew ; Simuni, Tanya ; Burghardt, Elliot ; Choi, Seung Ho ; Caspell-Garcia, Chelsea ; Chahine, Lana M. ; Mollenhauer, Brit ; Foroud, Tatiana ; Galasko, Douglas ; Merchant, Kalpana ; Arnedo, Vanessa ; Hutten, Samantha J. ; O’Grady, Alyssa N. ; Poston, Kathleen L. ; Tanner, Caroline M. ; Weintraub, Daniel ; Kieburtz, Karl ; Marek, Kenneth ; Coffey, Christopher S.</creator><creatorcontrib>Brumm, Michael C. ; Siderowf, Andrew ; Simuni, Tanya ; Burghardt, Elliot ; Choi, Seung Ho ; Caspell-Garcia, Chelsea ; Chahine, Lana M. ; Mollenhauer, Brit ; Foroud, Tatiana ; Galasko, Douglas ; Merchant, Kalpana ; Arnedo, Vanessa ; Hutten, Samantha J. ; O’Grady, Alyssa N. ; Poston, Kathleen L. ; Tanner, Caroline M. ; Weintraub, Daniel ; Kieburtz, Karl ; Marek, Kenneth ; Coffey, Christopher S. ; Parkinson’s Progression Markers Initiative ; on behalf of the Parkinson’s Progression Markers Initiative</creatorcontrib><description>Background:
Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.
Objective:
To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.
Methods:
Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.
Results:
Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639).
Conclusion:
Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.</description><identifier>ISSN: 1877-7171</identifier><identifier>EISSN: 1877-718X</identifier><identifier>DOI: 10.3233/JPD-223433</identifier><identifier>PMID: 37458046</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Activities of daily living ; Biomarkers ; Cerebrospinal fluid ; Cognitive ability ; Dopamine transporter ; Medical treatment ; Movement disorders ; Neurodegenerative diseases ; Parkinson's disease ; Research Report ; Synuclein</subject><ispartof>Journal of Parkinson's disease, 2023-01, Vol.13 (6), p.899-916</ispartof><rights>2023 – The authors. Published by IOS Press</rights><rights>Copyright IOS Press BV 2023</rights><rights>2023 – The authors. Published by IOS Press 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-89f5b853d948a274b73073549b862ff4e4eeccd83fdf383d9a017a67d5b86d4b3</citedby><cites>FETCH-LOGICAL-c439t-89f5b853d948a274b73073549b862ff4e4eeccd83fdf383d9a017a67d5b86d4b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,860,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37458046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brumm, Michael C.</creatorcontrib><creatorcontrib>Siderowf, Andrew</creatorcontrib><creatorcontrib>Simuni, Tanya</creatorcontrib><creatorcontrib>Burghardt, Elliot</creatorcontrib><creatorcontrib>Choi, Seung Ho</creatorcontrib><creatorcontrib>Caspell-Garcia, Chelsea</creatorcontrib><creatorcontrib>Chahine, Lana M.</creatorcontrib><creatorcontrib>Mollenhauer, Brit</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><creatorcontrib>Galasko, Douglas</creatorcontrib><creatorcontrib>Merchant, Kalpana</creatorcontrib><creatorcontrib>Arnedo, Vanessa</creatorcontrib><creatorcontrib>Hutten, Samantha J.</creatorcontrib><creatorcontrib>O’Grady, Alyssa N.</creatorcontrib><creatorcontrib>Poston, Kathleen L.</creatorcontrib><creatorcontrib>Tanner, Caroline M.</creatorcontrib><creatorcontrib>Weintraub, Daniel</creatorcontrib><creatorcontrib>Kieburtz, Karl</creatorcontrib><creatorcontrib>Marek, Kenneth</creatorcontrib><creatorcontrib>Coffey, Christopher S.</creatorcontrib><creatorcontrib>Parkinson’s Progression Markers Initiative</creatorcontrib><creatorcontrib>on behalf of the Parkinson’s Progression Markers Initiative</creatorcontrib><title>Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression</title><title>Journal of Parkinson's disease</title><addtitle>J Parkinsons Dis</addtitle><description>Background:
Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.
Objective:
To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.
Methods:
Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.
Results:
Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639).
Conclusion:
Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.</description><subject>Activities of daily living</subject><subject>Biomarkers</subject><subject>Cerebrospinal fluid</subject><subject>Cognitive ability</subject><subject>Dopamine transporter</subject><subject>Medical treatment</subject><subject>Movement disorders</subject><subject>Neurodegenerative diseases</subject><subject>Parkinson's disease</subject><subject>Research Report</subject><subject>Synuclein</subject><issn>1877-7171</issn><issn>1877-718X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><recordid>eNptkd9KwzAUxoMobqg3PoAEvBCEatOkTeaNzP_KhgMVvAtpm9bobDRpB7vzNXw9n8QjnXMDz00OnN_5zhc-hLZJeEAjSg9vRmdBFFFG6QrqEsF5wIl4XJ33nHTQlvfPIVRMEthZRx3KWSxClnRRM1LuxVTeVl8fnx6PnC2d9t7YCg9hop3H15WpjarNRB_hPh6asfa1rXRworzO8V3tVK3LKa4tHlpArcPLmmfGa0AXtTfRWqHGXm_N3g30cHF-f3oVDG4vr0_7gyBjtFcHolfEqYhp3mNCRZylnIacxqyXiiQqCqaZ1lmWC1rkBRWAqZBwlfActpKcpXQDHbe6b036qvNMV-B2LN-ceVVuKq0ycnlSmSdZ2okkYcxFRBgo7M4UnH1v4Ofy2TauAtMyAhNA0UgAtd9SmbPeO13MT5BQ_sQkISbZxgTwzqKpOfobCgB7LeBVqf_u_SP1Dcy8na8</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Brumm, Michael C.</creator><creator>Siderowf, Andrew</creator><creator>Simuni, Tanya</creator><creator>Burghardt, Elliot</creator><creator>Choi, Seung Ho</creator><creator>Caspell-Garcia, Chelsea</creator><creator>Chahine, Lana M.</creator><creator>Mollenhauer, Brit</creator><creator>Foroud, Tatiana</creator><creator>Galasko, Douglas</creator><creator>Merchant, Kalpana</creator><creator>Arnedo, Vanessa</creator><creator>Hutten, Samantha J.</creator><creator>O’Grady, Alyssa N.</creator><creator>Poston, Kathleen L.</creator><creator>Tanner, Caroline M.</creator><creator>Weintraub, Daniel</creator><creator>Kieburtz, Karl</creator><creator>Marek, Kenneth</creator><creator>Coffey, Christopher S.</creator><general>SAGE Publications</general><general>IOS Press BV</general><general>IOS Press</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20230101</creationdate><title>Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression</title><author>Brumm, Michael C. ; Siderowf, Andrew ; Simuni, Tanya ; Burghardt, Elliot ; Choi, Seung Ho ; Caspell-Garcia, Chelsea ; Chahine, Lana M. ; Mollenhauer, Brit ; Foroud, Tatiana ; Galasko, Douglas ; Merchant, Kalpana ; Arnedo, Vanessa ; Hutten, Samantha J. ; O’Grady, Alyssa N. ; Poston, Kathleen L. ; Tanner, Caroline M. ; Weintraub, Daniel ; Kieburtz, Karl ; Marek, Kenneth ; Coffey, Christopher S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-89f5b853d948a274b73073549b862ff4e4eeccd83fdf383d9a017a67d5b86d4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Activities of daily living</topic><topic>Biomarkers</topic><topic>Cerebrospinal fluid</topic><topic>Cognitive ability</topic><topic>Dopamine transporter</topic><topic>Medical treatment</topic><topic>Movement disorders</topic><topic>Neurodegenerative diseases</topic><topic>Parkinson's disease</topic><topic>Research Report</topic><topic>Synuclein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brumm, Michael C.</creatorcontrib><creatorcontrib>Siderowf, Andrew</creatorcontrib><creatorcontrib>Simuni, Tanya</creatorcontrib><creatorcontrib>Burghardt, Elliot</creatorcontrib><creatorcontrib>Choi, Seung Ho</creatorcontrib><creatorcontrib>Caspell-Garcia, Chelsea</creatorcontrib><creatorcontrib>Chahine, Lana M.</creatorcontrib><creatorcontrib>Mollenhauer, Brit</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><creatorcontrib>Galasko, Douglas</creatorcontrib><creatorcontrib>Merchant, Kalpana</creatorcontrib><creatorcontrib>Arnedo, Vanessa</creatorcontrib><creatorcontrib>Hutten, Samantha J.</creatorcontrib><creatorcontrib>O’Grady, Alyssa N.</creatorcontrib><creatorcontrib>Poston, Kathleen L.</creatorcontrib><creatorcontrib>Tanner, Caroline M.</creatorcontrib><creatorcontrib>Weintraub, Daniel</creatorcontrib><creatorcontrib>Kieburtz, Karl</creatorcontrib><creatorcontrib>Marek, Kenneth</creatorcontrib><creatorcontrib>Coffey, Christopher S.</creatorcontrib><creatorcontrib>Parkinson’s Progression Markers Initiative</creatorcontrib><creatorcontrib>on behalf of the Parkinson’s Progression Markers Initiative</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Parkinson's disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brumm, Michael C.</au><au>Siderowf, Andrew</au><au>Simuni, Tanya</au><au>Burghardt, Elliot</au><au>Choi, Seung Ho</au><au>Caspell-Garcia, Chelsea</au><au>Chahine, Lana M.</au><au>Mollenhauer, Brit</au><au>Foroud, Tatiana</au><au>Galasko, Douglas</au><au>Merchant, Kalpana</au><au>Arnedo, Vanessa</au><au>Hutten, Samantha J.</au><au>O’Grady, Alyssa N.</au><au>Poston, Kathleen L.</au><au>Tanner, Caroline M.</au><au>Weintraub, Daniel</au><au>Kieburtz, Karl</au><au>Marek, Kenneth</au><au>Coffey, Christopher S.</au><aucorp>Parkinson’s Progression Markers Initiative</aucorp><aucorp>on behalf of the Parkinson’s Progression Markers Initiative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression</atitle><jtitle>Journal of Parkinson's disease</jtitle><addtitle>J Parkinsons Dis</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>13</volume><issue>6</issue><spage>899</spage><epage>916</epage><pages>899-916</pages><issn>1877-7171</issn><eissn>1877-718X</eissn><abstract>Background:
Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.
Objective:
To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.
Methods:
Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.
Results:
Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639).
Conclusion:
Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>37458046</pmid><doi>10.3233/JPD-223433</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1877-7171 |
| ispartof | Journal of Parkinson's disease, 2023-01, Vol.13 (6), p.899-916 |
| issn | 1877-7171 1877-718X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10578214 |
| source | DOAJ Directory of Open Access Journals |
| subjects | Activities of daily living Biomarkers Cerebrospinal fluid Cognitive ability Dopamine transporter Medical treatment Movement disorders Neurodegenerative diseases Parkinson's disease Research Report Synuclein |
| title | Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression |
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