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Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F23%3A43921153" target="_blank" >RIV/00023752:_____/23:43921153 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00216208:11110/23:10458007 RIV/00216208:11120/23:43925240 RIV/00064165:_____/23:10458007

  • Výsledek na webu

    <a href="https://academic.oup.com/brain/article/146/8/3258/7071614" target="_blank" >https://academic.oup.com/brain/article/146/8/3258/7071614</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1093/brain/awad072" target="_blank" >10.1093/brain/awad072</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study

  • Popis výsledku v původním jazyce

    The neurodegenerative synucleinopathies, including Parkinson&apos;s disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points.In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson&apos;s disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson&apos;s disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects.Overall, 1160 subjects were followed over an average of 3.3 +/- 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson&apos;s disease and dementia with Lewy bodies phenoconverters was in cognitive testing.This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

  • Název v anglickém jazyce

    Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study

  • Popis výsledku anglicky

    The neurodegenerative synucleinopathies, including Parkinson&apos;s disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points.In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson&apos;s disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson&apos;s disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects.Overall, 1160 subjects were followed over an average of 3.3 +/- 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson&apos;s disease and dementia with Lewy bodies phenoconverters was in cognitive testing.This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30103 - Neurosciences (including psychophysiology)

Návaznosti výsledku

  • Projekt

  • Návaznosti

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Ostatní

  • Rok uplatnění

    2023

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Brain

  • ISSN

    0006-8950

  • e-ISSN

    1460-2156

  • Svazek periodika

    146

  • Číslo periodika v rámci svazku

    8

  • Stát vydavatele periodika

    US - Spojené státy americké

  • Počet stran výsledku

    15

  • Strana od-do

    3258-3272

  • Kód UT WoS článku

    000977958600001

  • EID výsledku v databázi Scopus

    2-s2.0-85167753835