Red-light photobiomodulation improves cognition and neuropsychiatric symptoms in post-stroke cognitive impairment: A randomized trial

Xuerong Huang¹Zihui Sun¹Weijie Wu¹Linli Lou¹Panpan Wang²Qin Wang²Yuanyu Fu²Liange Xu¹Mengwan Song¹Lidong Zhu¹Jin Huang¹Shaobo Ni¹Guangyong Chen¹Xueping Liu^3*Zhiqian Tong^2,4*

• ¹Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ²Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, School of Mental Health, Wenzhou Medical University, Wenzhou, China
• ³Shandong Provincial Hospital, Jinan, China
• ⁴Beijing Geriatric Hospital, Beijing, China

Introduction: Acute stroke patients often develop post-stroke cognitive impairment (PSCI) and dysthymic disorders. Formaldehyde (FA) induces cognitive decline and depression; while red light (RL) at 630 nm can degrade FA by activating FA-dehydrogenase (FDH). This study investigates the therapeutic effects of a novel RL device on cognitive function and neuropsychiatric symptoms in patients with PSCI. Methods: This was an exploratory, parallel-group, randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. Stroke patients (n=90) were enrolled. A total of 38 patients in the PSCI group and 44 patients in the PSCI-RL group completed the study. Participants were followed for 6 months, during which the intervention phase comprised 3 months of RL therapy or sham stimulation, followed by continued follow-up. Cognitive [Montreal Cognitive Assessment (MoCA)/Mini-Mental State Examination (MMSE)], neuropsychiatric [Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA)], and functional [Barthel Index (BI)] assessments were conducted at baseline and 6 months. Blood and urine levels of key enzymes and metabolites involved in FA metabolism were quantified, including semicarbazide-sensitive amine oxidase (SSAO, an FA-generating enzyme), FDH (an FA-degrading enzyme), cytochrome c (Cyt-c), FA, hydrogen peroxide (H₂O₂, a marker of FA generation), and coenzyme Q10 (CoQ10, an endogenous FA scavenger). Results: The phototherapy device improved cognitive abilities, reduced anxiety and depression, lessened stroke severity, and enhanced daily living activities in the PSCI-RL group at 6 months. Additionally, RL therapy altered FA metabolism, as it lowered SSAO and H2O2 levels and increased FDH, Cyt-c, and CoQ10 in blood and/or urine of PSCI patients. Conclusions: RL therapy may improve clinical symptoms in post-stroke patients by modulating FA metabolism, suggesting a safe and promising approach for treatment and rehabilitation.Trial registration: ChiCTR2200058991.