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Background and objectives <p>Age at onset is a key determinant of disease course in the general Parkinson’s disease (PD) population, but its influence among GBA-PD remains undetermined. This study investigates whether age at onset affects cognitive decline in GBA-PD patients and compares symptoms between GBA-PD and nonGBA-PD groups, stratified by age of onset.</p> Methods <p>In this multicentric cross-sectional study, PD patients were stratified into early onset (&lt; 50&#xa0;years), intermediate onset (50–60&#xa0;years), and late onset (&gt; 60&#xa0;years). Demographic–clinical data and scores of the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson’s Disease—Autonomic Dysfunction (SCOPA-AUT), and Beck Depression Inventory (BDI-II) were compared using ANCOVA. The effects of age of onset, <i>GBA1</i> status, and their interaction were investigated. External validation on cognition was performed using data from the PPMI cohort.</p> Results <p>We analyzed 80 GBA-PD and 236 nonGBA-PD patients. Among GBA-PD, late-onset patients exhibited worse axial scores (<i>p</i> = 0.037), while early-onset had more severe motor complications (<i>p</i> = 0.007) and dysautonomia (<i>p</i> = 0.012). Age of onset and <i>GBA1</i> status did not influence MoCA scores. Conversely, <i>GBA1</i> status independently affected MDS-UPDRS parts I and II (<i>p</i> &lt; 0.001 and <i>p</i> = 0.019, respectively) and BDI-II scores (<i>p</i> = 0.002). Analysis on the external dataset (PPMI) showed late-onset PD had lower MoCA scores (<i>p</i> &lt; 0.001) and confirmed <i>GBA1</i> status did not influence cognition.</p> Discussion <p>In the first decade of PD, cognitive decline is mainly age and duration dependent, irrespective of <i>GBA1</i> genotype. Early onset does not increase cognitive risk in GBA-PD, supporting its relevance for counseling and treatment planning.</p>

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The interplay between GBA1 status and age of onset on cognitive, motor and non-motor outcomes in Parkinson’s disease: multicenter cross-sectional study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月1日

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  • Claudia Ledda,
  • Silvia Gallo,
  • Micol Avenali,
  • Carlo Alberto Artusi,
  • Gabriele Imbalzano,
  • Francesca Donetto,
  • Elisa Montanaro,
  • Alberto Romagnolo,
  • Pierfrancesco Mitrotti,
  • Luca Gallo,
  • Rosa De Micco,
  • Valeria Sant’Elia,
  • Mattia Siciliano,
  • Alessandro Tessitore,
  • Giovanna Calandra-Buonaura,
  • Giulia Giannini,
  • Luisa Sambati,
  • Leonardo Lopiano,
  • Enza Maria Valente,
  • Marco Bozzali

摘要

Background and objectives

Age at onset is a key determinant of disease course in the general Parkinson’s disease (PD) population, but its influence among GBA-PD remains undetermined. This study investigates whether age at onset affects cognitive decline in GBA-PD patients and compares symptoms between GBA-PD and nonGBA-PD groups, stratified by age of onset.

Methods

In this multicentric cross-sectional study, PD patients were stratified into early onset (< 50 years), intermediate onset (50–60 years), and late onset (> 60 years). Demographic–clinical data and scores of the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson’s Disease—Autonomic Dysfunction (SCOPA-AUT), and Beck Depression Inventory (BDI-II) were compared using ANCOVA. The effects of age of onset, GBA1 status, and their interaction were investigated. External validation on cognition was performed using data from the PPMI cohort.

Results

We analyzed 80 GBA-PD and 236 nonGBA-PD patients. Among GBA-PD, late-onset patients exhibited worse axial scores (p = 0.037), while early-onset had more severe motor complications (p = 0.007) and dysautonomia (p = 0.012). Age of onset and GBA1 status did not influence MoCA scores. Conversely, GBA1 status independently affected MDS-UPDRS parts I and II (p < 0.001 and p = 0.019, respectively) and BDI-II scores (p = 0.002). Analysis on the external dataset (PPMI) showed late-onset PD had lower MoCA scores (p < 0.001) and confirmed GBA1 status did not influence cognition.

Discussion

In the first decade of PD, cognitive decline is mainly age and duration dependent, irrespective of GBA1 genotype. Early onset does not increase cognitive risk in GBA-PD, supporting its relevance for counseling and treatment planning.