{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:06:04Z","timestamp":1788231964205,"version":"build-2803163510"},"reference-count":30,"publisher":"The Korean Movement Disorder Society","issue":"2","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["e-jmd.org"],"crossmark-restriction":true},"short-container-title":["JMD"],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:p>Objective Continuous subcutaneous foslevodopa\/foscarbidopa infusion (CSFLI) represents a transformative therapy for advanced Parkinson\u2019s disease (aPD), but real-world neuropsychiatric safety data remain limited, particularly in populations typically excluded from clinical trials. This study aimed to assess the frequency, clinical patterns, and predictors of neuropsychiatric and\/or cognitive worsening in a real-world CSFLI-treated cohort.Methods We performed a retrospective observational study involving 36 consecutive aPD patients who underwent CSFLI with a six-month follow-up. Neuropsychiatric\/cognitive worsening was defined as any clinically meaningful increase in the Movement Disorder Society\u2013Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) Part I or the Parkinson\u2019s Disease Questionnaire-8 (PDQ-8) cognitive\/psychiatric subscores. Patients were classified as \u201cworsening\u201d versus \u201cno worsening\u201d and compared with respect to baseline characteristics. Predictors were identified using univariable and exploratory multivariable analyses.Results Seventeen patients (47.2%) experienced neuropsychiatric\/cognitive worsening within six months. Critically, patients with prior confusion or hallucinations who were managed with baseline clozapine had significantly better outcomes: confusion history was common in 57.9% of the patients in the stable group versus 11.8% in the worsening group (&lt;i&gt;p&lt;\/i&gt;=0.006), with clozapine use corresponding to 63.2% of the patients versus 23.5% (&lt;i&gt;p&lt;\/i&gt;=0.023). Conversely, catechol-O-methyltransferase inhibitor (COMT-I) use was more frequent in the worsening group (70.6% vs. 21.1%, &lt;i&gt;p&lt;\/i&gt;=0.006). Motor outcomes remained stable at 6 months regardless of the patient\u2019s neuropsychiatric status.Conclusion In a vulnerable real-world aPD population, neuropsychiatric\/cognitive worsening under CSFLI was more frequent than it was in pivotal trials (47% vs. 7%\u201317%) but was generally mild and not associated with motor deterioration. Importantly, proactive clozapine use enabled safe CSFLI treatment in patients with psychiatric histories traditionally considered high risk. COMT-I emerged as a modifiable risk factor. These findings support broader CSFLI use with structured neuropsychiatric monitoring and proactive clozapine in selected patients.<\/jats:p>","DOI":"10.14802\/jmd.25304","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T23:54:05Z","timestamp":1769385245000},"page":"178-186","update-policy":"https:\/\/doi.org\/10.14802\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuropsychiatric and Cognitive Safety of Subcutaneous Foslevodopa\/Foscarbidopa in Advanced Parkinson\u2019s Disease: Insights From a Real-World Cohort"],"prefix":"10.14802","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-9590","authenticated-orcid":true,"given":"Cl\u00e9ment","family":"Desjardins","sequence":"first","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne de Saint","family":"Vaulry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Salardaine","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Rosset","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Brandel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Baille","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fondation Rothschild Hospital, Paris Cit\u00e9 University, Paris, 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