Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned

Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson’s disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably diffe...

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Main Authors: Heinzel, Sebastian, Roeben, Benjamin, Ben-Shlomo, Yoav, Lerche, Stefanie, Alves, Guido, Barone, Paolo, Behnke, Stefanie, Berendse, Henk W., Bloem, Bastiaan R., Burn, David, Dodel, Richard, Grosset, Donald G., Hu, Michele, Kasten, Meike, Krüger, Rejko, Moccia, Marcello, Mollenhauer, Brit, Oertel, Wolfgang, Suenkel, Ulrike, Walter, Uwe, Wirdefeldt, Karin, Liepelt-Scarfone, Inga, Maetzler, Walter, Berg, Daniela
Format: Online
Language:English
Published: Frontiers Media S.A. 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916171/
id pubmed-4916171
recordtype oai_dc
spelling pubmed-49161712016-07-21 Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned Heinzel, Sebastian Roeben, Benjamin Ben-Shlomo, Yoav Lerche, Stefanie Alves, Guido Barone, Paolo Behnke, Stefanie Berendse, Henk W. Bloem, Bastiaan R. Burn, David Dodel, Richard Grosset, Donald G. Hu, Michele Kasten, Meike Krüger, Rejko Moccia, Marcello Mollenhauer, Brit Oertel, Wolfgang Suenkel, Ulrike Walter, Uwe Wirdefeldt, Karin Liepelt-Scarfone, Inga Maetzler, Walter Berg, Daniela Neuroscience A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson’s disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies. Frontiers Media S.A. 2016-06-22 /pmc/articles/PMC4916171/ /pubmed/27445791 http://dx.doi.org/10.3389/fnagi.2016.00147 Text en Copyright © 2016 Heinzel, Roeben, Ben-Shlomo, Lerche, Alves, Barone, Behnke, Berendse, Bloem, Burn, Dodel, Grosset, Hu, Kasten, Krüger, Moccia, Mollenhauer, Oertel, Suenkel, Walter, Wirdefeldt, Liepelt-Scarfone, Maetzler and Berg. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Heinzel, Sebastian
Roeben, Benjamin
Ben-Shlomo, Yoav
Lerche, Stefanie
Alves, Guido
Barone, Paolo
Behnke, Stefanie
Berendse, Henk W.
Bloem, Bastiaan R.
Burn, David
Dodel, Richard
Grosset, Donald G.
Hu, Michele
Kasten, Meike
Krüger, Rejko
Moccia, Marcello
Mollenhauer, Brit
Oertel, Wolfgang
Suenkel, Ulrike
Walter, Uwe
Wirdefeldt, Karin
Liepelt-Scarfone, Inga
Maetzler, Walter
Berg, Daniela
spellingShingle Heinzel, Sebastian
Roeben, Benjamin
Ben-Shlomo, Yoav
Lerche, Stefanie
Alves, Guido
Barone, Paolo
Behnke, Stefanie
Berendse, Henk W.
Bloem, Bastiaan R.
Burn, David
Dodel, Richard
Grosset, Donald G.
Hu, Michele
Kasten, Meike
Krüger, Rejko
Moccia, Marcello
Mollenhauer, Brit
Oertel, Wolfgang
Suenkel, Ulrike
Walter, Uwe
Wirdefeldt, Karin
Liepelt-Scarfone, Inga
Maetzler, Walter
Berg, Daniela
Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
author_facet Heinzel, Sebastian
Roeben, Benjamin
Ben-Shlomo, Yoav
Lerche, Stefanie
Alves, Guido
Barone, Paolo
Behnke, Stefanie
Berendse, Henk W.
Bloem, Bastiaan R.
Burn, David
Dodel, Richard
Grosset, Donald G.
Hu, Michele
Kasten, Meike
Krüger, Rejko
Moccia, Marcello
Mollenhauer, Brit
Oertel, Wolfgang
Suenkel, Ulrike
Walter, Uwe
Wirdefeldt, Karin
Liepelt-Scarfone, Inga
Maetzler, Walter
Berg, Daniela
author_sort Heinzel, Sebastian
title Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
title_short Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
title_full Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
title_fullStr Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
title_full_unstemmed Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned
title_sort prodromal markers in parkinson’s disease: limitations in longitudinal studies and lessons learned
description A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson’s disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.
publisher Frontiers Media S.A.
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916171/
_version_ 1613597846230007808

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