1. Academic Validation
  2. Levodopa-synergistic CBT intervention improves Parkinson's disease with anxiety disorder by regulating the BDNF/PI3K/AKT pathway

Levodopa-synergistic CBT intervention improves Parkinson's disease with anxiety disorder by regulating the BDNF/PI3K/AKT pathway

  • Neurol Sci. 2025 Feb 12. doi: 10.1007/s10072-025-07988-0.
Niu Ji # 1 2 Shujin Lu # 1 3 Bingchao Xu 2 Xinying Guan 2 Zhenping Xian 2 Deqin Geng 4 5 Dianshuai Gao # 6 7
Affiliations

Affiliations

  • 1 Nanjing Medical University, No. 101, Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, 211166, China.
  • 2 The First People's Hospital of Lianyungang, Lianyungang, Jiangsu Province, 222000, China.
  • 3 Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road, Xuzhou, Jiangsu Province, 221002, China.
  • 4 Nanjing Medical University, No. 101, Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, 211166, China. deqingeng@163.com.
  • 5 Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road, Xuzhou, Jiangsu Province, 221002, China. deqingeng@163.com.
  • 6 Nanjing Medical University, No. 101, Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, 211166, China. gds@xzhmu.edu.cn.
  • 7 School of Basic Medical Sciences, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou, Jiangsu Province, 221004, China. gds@xzhmu.edu.cn.
  • # Contributed equally.
Abstract

Background: Anxiety disorder is one of the most common and disabling neuropsychiatric syndromes in patients with Parkinson's disease (PD), seriously affecting the quality of life and prognosis of PD patients.

Objective: The objective of this study was to analyze the risk factors for anxiety in PD patients and to evaluate the effectiveness of cognitive behavioral therapy (CBT) in treating PD with anxiety disorder (PDAD).

Methods: Baseline data were recorded for 211 PD patients and 139 PDAD patients, and multi-factorial and independent risk factors for anxiety disorder in PD patients were analyzed. ​The 139 PDAD patients were divided into clinical testing (CMO) and CBT groups. Assessments were taken at baseline and after the end of the intervention. A 5-month follow-up survey was conducted after the intervention. The mouse PD model was induced by MPTP, and the anxiety state of mice was detected by rotarod test and open-field test. The expression of BDNF/PI3K/Akt protein in serum and mouse brain was detected by western blot.

Results: PDAD patients had significantly higher HAMA scores than PD patients. PSQI, ESS, HAMD, SCOPA-AUT, UPDRS-III and Hoehn-Yahr were independent risk factors for anxiety disorder in PD patients. After the intervention, the psychological state, cognitive function and quality of life improved in both the CMO and CBT groups, with the CBT group showing better improvement Results from follow-up showed that the number and frequency of falls was lower in the CBT group than in the CMO group, and that patients were more satisfied with the CBT intervention than the CMO group. L-dopa treatment alleviated anxiety in PD mice. L-dopa treatment increased BDNF, p-PI3K, and p-Akt protein levels. Moreover, the combination of L-dopa and CBT enhanced the boosting effect of L-dopa on these proteins.

Conclusion: CBT is an effective treatment for anxiety in patients with Parkinson's disease. Medications combined with CBT have been shown to be effective in improving depression, anxiety and quality of life in PDAD patients.

Keywords

Anxiety disorder; BDNF; Cognitive behavioral therapy; PI3K/Akt; Parkinson's disease.

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