帕金森认知障碍的临床研究进展
Research Advances in Cognitive Impairment in Parkinson’s Disease
摘要: 帕金森病认知障碍是帕金森病(Parkinson’s disease, PD)最主要的非运动并发症之一，涵盖帕金森病轻度认知障碍(Parkinson’s disease-mild cognitive impairment, PD-MCI)至帕金森病痴呆(Parkinson’s disease dementia, PDD)的完整疾病谱，是决定患者临床预后、加重疾病负担与家庭照护压力的核心因素。多项Meta分析一致证实，PD-MCI在PD患者中的总体患病率达40%；高龄、载脂蛋白E (apolipoprotein E, APOE) ε4基因型、葡萄糖脑苷脂酶(glucocerebrosidase, GBA)基因突变、快速眼动睡眠行为障碍(rapid eye movement sleep behavior disorder, RBD)及神经精神症状等，是PD患者认知功能进展的独立危险因素；神经影像标志物、体液生物标志物及主观认知抱怨，可实现PD认知障碍的早期预警。本文基于高等级循证医学证据，系统梳理PD认知障碍的流行病学特征、病理生理机制、风险预测体系、评估诊断标准与临床管理策略的最新研究进展，总结当前领域存在的核心局限，旨在为PD认知障碍的临床规范化诊疗、高风险人群早期筛查与科研方向选择提供循证参考。
Abstract: Cognitive impairment in Parkinson’s disease (PD-CI) is one of the most prominent non-motor complications of Parkinson’s disease (PD). It covers the full disease spectrum from Parkinson’s disease-mild cognitive impairment (PD-MCI) to Parkinson’s disease dementia (PDD), and serves as a key determinant of patients’ clinical prognosis as well as a major contributor to elevated disease burden and family caregiving stress. Multiple meta-analyses have consistently demonstrated that PD-MCI has an overall prevalence of 40% among PD patients. Advanced age, apolipoprotein E (APOE) ε4 genotype, glucocerebrosidase (GBA) gene mutations, rapid eye movement sleep behavior disorder (RBD), and neuropsychiatric symptoms are independent risk factors for cognitive progression in PD patients. Neuroimaging biomarkers, humoral biomarkers, and subjective cognitive complaints (SCCs) enable the early warning of PD-CI. Based on high-level evidence-based medical evidence, this review systematically summarizes the latest research advances in the epidemiological characteristics, pathophysiological mechanisms, risk prediction systems, diagnostic evaluation criteria, and clinical management strategies of PD-CI, and outlines the key limitations in the current research field. This work aims to provide evidence-based references for the standardized clinical diagnosis and treatment of PD-CI, early screening of high-risk populations, and the selection of future research directions.
文章引用：雒思成. 帕金森认知障碍的临床研究进展[J]. 临床医学进展, 2026, 16(5): 3492-3501. https://doi.org/10.12677/acm.2026.1652172

参考文献

[1] Weintraub, D., Aarsland, D., Biundo, R., Dobkin, R., Goldman, J. and Lewis, S. (2022) Management of Psychiatric and Cognitive Complications in Parkinson’s Disease. British Medical Journal, 379, e068718. [Google Scholar] [CrossRef] [PubMed]
[2] Getz, S.J. and Levin, B. (2017) Cognitive and Neuropsychiatric Features of Early Parkinson’s Disease. Archives of Clinical Neuropsychology, 32, 769-785. [Google Scholar] [CrossRef] [PubMed]
[3] Rektorova, I. (2019) Current Treatment of Behavioral and Cognitive Symptoms of Parkinson’s Disease. Parkinsonism & Related Disorders, 59, 65-73. [Google Scholar] [CrossRef] [PubMed]
[4] Yang, J., Pourzinal, D., Byrne, G.J., McMahon, K.L., Copland, D.A., O’Sullivan, J.D., et al. (2023) Global Assessment, Cognitive Profile, and Characteristics of Mild Cognitive Impairment in Parkinson’s Disease. International Journal of Geriatric Psychiatry, 38, e5955. [Google Scholar] [CrossRef] [PubMed]
[5] Baiano, C., Barone, P., Trojano, L. and Santangelo, G. (2020) Prevalence and Clinical Aspects of Mild Cognitive Impairment in Parkinson's Disease: A Meta-Analysis. Movement Disorders, 35, 45-54. [Google Scholar] [CrossRef] [PubMed]
[6] Ryman, S.G. and Poston, K.L. (2020) MRI Biomarkers of Motor and Non-Motor Symptoms in Parkinson’s Disease. Parkinsonism & Related Disorders, 73, 85-93. [Google Scholar] [CrossRef] [PubMed]
[7] Hirano, S. (2021) Clinical Implications for Dopaminergic and Functional Neuroimage Research in Cognitive Symptoms of Parkinson’s Disease. Molecular Medicine, 27, Article No. 40. [Google Scholar] [CrossRef] [PubMed]
[8] Deng, X., Mehta, A., Xiao, B., Ray Chaudhuri, K., Tan, E. and Tan, L.C. (2025) Parkinson’s Disease Subtypes: Approaches and Clinical Implications. Parkinsonism & Related Disorders, 130, Article 107208. [Google Scholar] [CrossRef] [PubMed]
[9] Goldman, J.G., Holden, S.K., Litvan, I., McKeith, I., Stebbins, G.T. and Taylor, J. (2018) Evolution of Diagnostic Criteria and Assessments for Parkinson’s Disease Mild Cognitive Impairment. Movement Disorders, 33, 503-510. [Google Scholar] [CrossRef] [PubMed]
[10] Maggi, G., Trojano, L., Barone, P. and Santangelo, G. (2021) Sleep Disorders and Cognitive Dysfunctions in Parkinson’s Disease: A Meta-Analytic Study. Neuropsychology Review, 31, 643-682. [Google Scholar] [CrossRef] [PubMed]
[11] Lenka, A., Hegde, S., Arumugham, S.S., Singh, P., Yadav, R. and Pal, P.K. (2023) Cognitive Correlates of Visual and Minor Hallucinations in Parkinson’s Disease. Canadian Journal of Neurological Sciences, 50, 44-48. [Google Scholar] [CrossRef] [PubMed]
[12] Szwedo, A.A., Dalen, I., Pedersen, K.F., Camacho, M., Bäckström, D., Forsgren, L., et al. (2022) GBA and APOE Impact Cognitive Decline in Parkinson’s Disease: A 10-Year Population-Based Study. Movement Disorders, 37, 1016-1027. [Google Scholar] [CrossRef] [PubMed]
[13] Thaler, A., Livne, V., Rubinstein, E., Omer, N., Faust-Socher, A., Cohen, B., et al. (2024) Mild Cognitive Impairment among LRRK2 and GBA1 Patients with Parkinson’s Disease. Parkinsonism & Related Disorders, 123, Article 106970. [Google Scholar] [CrossRef] [PubMed]
[14] Weintraub, D., Caspell-Garcia, C., Simuni, T., Cho, H.R., Coffey, C.S., Aarsland, D., et al. (2020) Neuropsychiatric Symptoms and Cognitive Abilities over the Initial Quinquennium of Parkinson Disease. Annals of Clinical and Translational Neurology, 7, 449-461. [Google Scholar] [CrossRef] [PubMed]
[15] Jozwiak, N., Postuma, R.B., Montplaisir, J., Latreille, V., Panisset, M., Chouinard, S., et al. (2017) REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson’s Disease. Sleep, 40, zsx101. [Google Scholar] [CrossRef] [PubMed]
[16] Oltra, J., Segura, B., Uribe, C., Monté-Rubio, G.C., Campabadal, A., Inguanzo, A., et al. (2021) Sex Differences in Brain Atrophy and Cognitive Impairment in Parkinson’s Disease Patients with and without Probable Rapid Eye Movement Sleep Behavior Disorder. Journal of Neurology, 269, 1591-1599. [Google Scholar] [CrossRef] [PubMed]
[17] Devignes, Q., Bordier, C., Viard, R., Defebvre, L., Kuchcinski, G., Leentjens, A.F.G., et al. (2021) Resting-State Functional Connectivity in Frontostriatal and Posterior Cortical Subtypes in Parkinson’s Disease-Mild Cognitive Impairment. Movement Disorders, 37, 502-512. [Google Scholar] [CrossRef] [PubMed]
[18] Curtis, A.F., Masellis, M., Camicioli, R., Davidson, H. and Tierney, M.C. (2019) Cognitive Profile of Non-Demented Parkinson’s Disease: Meta-Analysis of Domain and Sex-Specific Deficits. Parkinsonism & Related Disorders, 60, 32-42. [Google Scholar] [CrossRef] [PubMed]
[19] van der Zee, S., Kanel, P., Gerritsen, M.J.J., Boertien, J.M., Slomp, A.C., Müller, M.L.T.M., et al. (2022) Altered Cholinergic Innervation in De Novo Parkinson’s Disease with and without Cognitive Impairment. Movement Disorders, 37, 713-723. [Google Scholar] [CrossRef] [PubMed]
[20] Montagnese, M., Vignando, M., Ffytche, D. and Mehta, M.A. (2022) Cognitive and Visual Processing Performance in Parkinson’s Disease Patients with vs without Visual Hallucinations: A Meta-Analysis. Cortex, 146, 161-172. [Google Scholar] [CrossRef] [PubMed]
[21] Meng, D., Jin, Z., Wang, Y. and Fang, B. (2023) Longitudinal Cognitive Changes in Patients with Early Parkinson’s Disease and Neuropsychiatric Symptoms. CNS Neuroscience & Therapeutics, 29, 2259-2266. [Google Scholar] [CrossRef] [PubMed]
[22] Chen, X. and Zhang, Y. (2024) A Review of the Neurotransmitter System Associated with Cognitive Function of the Cerebellum in Parkinson’s Disease. Neural Regeneration Research, 19, 324-330. [Google Scholar] [CrossRef] [PubMed]
[23] Owens-Walton, C., Jakabek, D., Power, B.D., Walterfang, M., Hall, S., van Westen, D., et al. (2021) Structural and Functional Neuroimaging Changes Associated with Cognitive Impairment and Dementia in Parkinson’s Disease. Psychiatry Research: Neuroimaging, 312, Article 111273. [Google Scholar] [CrossRef] [PubMed]
[24] Labrador-Espinosa, M.A., Silva-Rodríguez, J., Reina-Castillo, M.I., Mir, P. and Grothe, M.J. (2023) Basal Forebrain Atrophy, Cortical Thinning, and Amyloid-β Status in Parkinson’s Disease-Related Cognitive Decline. Movement Disorders, 38, 1871-1880. [Google Scholar] [CrossRef] [PubMed]
[25] McDonald, C., Newton, J.L. and Burn, D.J. (2016) Orthostatic Hypotension and Cognitive Impairment in Parkinson’s Disease: Causation or Association? Movement Disorders, 31, 937-946. [Google Scholar] [CrossRef] [PubMed]
[26] Zhu, Z., Cordato, D., Chen, R., Xu, Y.H., Shulruf, B. and Chan, D.K.Y. (2025) Plasma Alpha-Synuclein Predicts Cognitive Impairment in Parkinson’s Disease: A Systematic Review and Meta-Analysis. Journal of Neurology, 272, Article No. 124. [Google Scholar] [CrossRef] [PubMed]
[27] Fereshtehnejad, S.M., Zeighami, Y., Dagher, A. and Postuma, R.B. (2017) Clinical Criteria for Subtyping Parkinson’s Disease: Biomarkers and Longitudinal Progression. Brain, 140, 1959-1976. [Google Scholar] [CrossRef] [PubMed]
[28] Paul, K.C., Rausch, R., Creek, M.M., Sinsheimer, J.S., Bronstein, J.M., Bordelon, Y., et al. (2016) APOE, MAPT, and COMT and Parkinson’s Disease Susceptibility and Cognitive Symptom Progression. Journal of Parkinson’s Disease, 6, 349-359. [Google Scholar] [CrossRef] [PubMed]
[29] Mihaescu, A.S., Valli, M., Uribe, C., Diez-Cirarda, M., Masellis, M., Graff-Guerrero, A., et al. (2022) Beta Amyloid Deposition and Cognitive Decline in Parkinson’s Disease: A Study of the PPMI Cohort. Molecular Brain, 15, Article No. 79. [Google Scholar] [CrossRef] [PubMed]
[30] Wood, K.H., Nenert, R., Miften, A.M., Kent, G.W., Sleyster, M., Memon, R.A., et al. (2024) Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson’s Disease. Movement Disorders, 39, 1504-1513. [Google Scholar] [CrossRef] [PubMed]
[31] Carvalho de Abreu, D.C., Pieruccini-Faria, F., Son, S., Montero-Odasso, M. and Camicioli, R. (2024) Is White Matter Hyperintensity Burden Associated with Cognitive and Motor Impairment in Patients with Parkinson’s Disease? A Systematic Review and Meta-Analysis. Neuroscience & Biobehavioral Reviews, 161, Article 105677. [Google Scholar] [CrossRef] [PubMed]
[32] Zeidan, O., Jaragh, N., Tama, M., Alkhalifa, M., Alqayem, M. and Butler, A.E. (2025) The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson’s Disease: A Systematic Review. International Journal of Molecular Sciences, 26, Article 8078. [Google Scholar] [CrossRef] 
[33] Zhu, B., Park, J., Coffey, S.R., Russo, A., Hsu, I., Wang, J., et al. (2024) Single-Cell Transcriptomic and Proteomic Analysis of Parkinson’s Disease Brains. Science Translational Medicine, 16, eabo1997. [Google Scholar] [CrossRef] [PubMed]
[34] Zhang, W., Xiao, D., Mao, Q. and Xia, H. (2023) Role of Neuroinflammation in Neurodegeneration Development. Signal Transduction and Targeted Therapy, 8, Article No. 267. [Google Scholar] [CrossRef] [PubMed]
[35] Kouli, A., Camacho, M., Allinson, K. and Williams-Gray, C.H. (2020) Neuroinflammation and Protein Pathology in Parkinson’s Disease Dementia. Acta Neuropathologica Communications, 8, Article No. 211. [Google Scholar] [CrossRef] [PubMed]
[36] Kouli, A., Spindler, L.R.B., Fryer, T.D., Hong, Y.T., Malpetti, M., Aigbirhio, F.I., et al. (2024) Neuroinflammation Is Linked to Dementia Risk in Parkinson’s Disease. Brain, 147, 923-935. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, R., Sun, H., Cao, Y., Zhang, Z., Chen, Y., Wang, X., et al. (2024) Glucosylceramide Accumulation in Microglia Triggers STING-Dependent Neuroinflammation and Neurodegeneration in Mice. Science Signaling, 17, eadk8249. [Google Scholar] [CrossRef] [PubMed]
[38] Boyd, R.J., Avramopoulos, D., Jantzie, L.L. and McCallion, A.S. (2022) Neuroinflammation Represents a Common Theme Amongst Genetic and Environmental Risk Factors for Alzheimer and Parkinson Diseases. Journal of Neuroinflammation, 19, Article No. 223. [Google Scholar] [CrossRef] [PubMed]
[39] Clasen, F., Yildirim, S., Arıkan, M., Garcia-Guevara, F., Hanoğlu, L., Yılmaz, N.H., et al. (2025) Microbiome Signatures of Virulence in the Oral-Gut-Brain Axis Influence Parkinson’s Disease and Cognitive Decline Pathophysiology. Gut Microbes, 17, Article 2506843. [Google Scholar] [CrossRef] [PubMed]
[40] Zhang, R., Ding, N., Feng, X. and Liao, W. (2025) The Gut Microbiome, Immune Modulation, and Cognitive Decline: Insights on the Gut-Brain Axis. Frontiers in Immunology, 16, Article 1529958. [Google Scholar] [CrossRef] [PubMed]
[41] Kalyanaraman, B., Cheng, G. and Hardy, M. (2024) Gut Microbiome, Short-Chain Fatty Acids, Alpha-Synuclein, Neuroinflammation, and ROS/RNS: Relevance to Parkinson’s Disease and Therapeutic Implications. Redox Biology, 71, Article 103092. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E. and Pettersson, S. (2021) The Role of Gut Dysbiosis in Parkinson’s Disease: Mechanistic Insights and Therapeutic Options. Brain, 144, 2571-2593. [Google Scholar] [CrossRef] [PubMed]
[43] Yang, Y., Stewart, T., Zhang, C., Wang, P., Xu, Z., Jin, J., et al. (2024) Erythrocytic α-Synuclein and the Gut Microbiome: Kindling of the Gut-Brain Axis in Parkinson’s Disease. Movement Disorders, 39, 40-52. [Google Scholar] [CrossRef] [PubMed]
[44] Tan, A.H., Lim, S.Y. and Lang, A.E. (2022) The Microbiome-Gut-Brain Axis in Parkinson Disease—From Basic Research to the Clinic. Nature Reviews Neurology, 18, 476-495. [Google Scholar] [CrossRef] [PubMed]
[45] Guo, Y., Liu, F.T., Hou, X.H., et al. (2021) Predictors of Cognitive Impairment in Parkinson’s Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Journal of Neurology, 268, 2713-2722. [Google Scholar] [CrossRef] [PubMed]
[46] Trompeta, C., Gasca-Salas, C., Rodríguez-Rojas, R., Fernández-Rodríguez, B., Clarimón, J., García-Cañamaque, L., et al. (2025) Apolipoprotein E Genotypes and Amyloid Burden Associated with Cognitive Decline in Non-Demented Parkinson’s Disease Patients: A Preliminary Analysis. Journal of the Neurological Sciences, 473, Article 123510. [Google Scholar] [CrossRef] [PubMed]
[47] Bäckström, D., Eriksson Domellöf, M., Granåsen, G., Linder, J., Mayans, S., Elgh, E., et al. (2018) Polymorphisms in Dopamine-Associated Genes and Cognitive Decline in Parkinson’s Disease. Acta Neurologica Scandinavica, 137, 91-98. [Google Scholar] [CrossRef] [PubMed]
[48] Siciliano, M., Tessitore, A., Morgante, F., Goldman, J.G. and Ricciardi, L. (2024) Subjective Cognitive Complaints in Parkinson’s Disease: A Systematic Review and Meta-Analysis. Movement Disorders, 39, 17-28. [Google Scholar] [CrossRef] [PubMed]
[49] Hlavnička, J., Mana, J., Bezdicek, O., Čihák, M., Havlík, F., Škrabal, D., et al. (2025) Four Questions to Predict Cognitive Decline in de novo Parkinson’s Disease. npj Parkinson’s Disease, 11, Article No. 91. [Google Scholar] [CrossRef] [PubMed]
[50] D’Iorio, A., Maggi, G., Vitale, C., Trojano, L. and Santangelo, G. (2018) “Pure Apathy” and Cognitive Dysfunctions in Parkinson’s Disease: A Meta-Analytic Study. Neuroscience & Biobehavioral Reviews, 94, 1-10. [Google Scholar] [CrossRef] [PubMed]
[51] Timblin, H., Rahmani, E., Ryczek, C.A., Hill, C.R. and Jones, J.D. (2022) Physical Inactivity Links Depressive Symptoms and Cognitive Functioning among Individuals with Parkinson’s Disease. Neuropsychology, 36, 505-512. [Google Scholar] [CrossRef] [PubMed]
[52] Reheman, M., Buch, S., He, N., Huang, P., Yu, Q., Wang, X., et al. (2025) White Matter Hyperintensity Tissue Property Spatial Variations as a Function of Cognitive Status in Parkinson’s Disease. NeuroImage, 312, Article 121236. [Google Scholar] [CrossRef] [PubMed]
[53] Biondetti, E., Santin, M.D., Valabrègue, R., Mangone, G., Gaurav, R., Pyatigorskaya, N., et al. (2021) The Spatiotemporal Changes in Dopamine, Neuromelanin and Iron Characterizing Parkinson’s Disease. Brain, 144, 3114-3125. [Google Scholar] [CrossRef] [PubMed]
[54] Liu, T., Zuo, H., Ma, D., Song, D., Zhao, Y. and Cheng, O. (2023) Cerebrospinal Fluid GFAP Is a Predictive Biomarker for Conversion to Dementia and Alzheimer’s Disease-Associated Biomarkers Alterations among De Novo Parkinson’s Disease Patients: A Prospective Cohort Study. Journal of Neuroinflammation, 20, Article No. 167. [Google Scholar] [CrossRef] [PubMed]
[55] Delgado-Alvarado, M., Gago, B., Navalpotro-Gomez, I., Jiménez-Urbieta, H. and Rodriguez-Oroz, M.C. (2016) Biomarkers for Dementia and Mild Cognitive Impairment in Parkinson’s Disease. Movement Disorders, 31, 861-881. [Google Scholar] [CrossRef] [PubMed]
[56] Dijkstra, F., de Volder, I., Viaene, M., Cras, P. and Crosiers, D. (2022) Polysomnographic Predictors of Sleep, Motor, and Cognitive Dysfunction Progression in Parkinson’s Disease. Current Neurology and Neuroscience Reports, 22, 657-674. [Google Scholar] [CrossRef] [PubMed]
[57] Litvan, I., Goldman, J.G., Tröster, A.I., Schmand, B.A., Weintraub, D., Petersen, R.C., et al. (2012) Diagnostic Criteria for Mild Cognitive Impairment in Parkinson’s Disease: Movement Disorder Society Task Force Guidelines. Movement Disorders, 27, 349-356. [Google Scholar] [CrossRef] [PubMed]
[58] Weintraub, D., Tröster, A.I., Marras, C. and Stebbins, G. (2018) Initial Cognitive Changes in Parkinson’s Disease. Movement Disorders, 33, 511-519. [Google Scholar] [CrossRef] [PubMed]
[59] 邵文丽, 赵羚, 吴凡, 等. 蒙特利尔认知评估量表在老年神经认知障碍中的诊断价值[J]. 中国老年学杂志, 2021, 41(16): 3551-3554.
[60] 薛晓帆, 吴志悦, 黄安琪, 等. 中国人群帕金森病轻度认知障碍综合认知域评估量表的筛选及诊断效度分析[J]. 中风与神经疾病杂志, 2024, 41(5): 402-407.
[61] Weintraub, D., Marras, C., Amara, A., Anderson, K.E., Chahine, L.M., Eberly, S., et al. (2024) Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson’s Disease. Movement Disorders, 39, 706-714. [Google Scholar] [CrossRef] [PubMed]
[62] Litvan, I., Kieburtz, K., Tröster, A.I. and Aarsland, D. (2018) Strengths and Challenges in Conducting Clinical Trials in Parkinson’s Disease Mild Cognitive Impairment. Movement Disorders, 33, 520-527. [Google Scholar] [CrossRef] [PubMed]
[63] Bu, S., Liu, W., Sheng, X., Jin, L. and Zhao, Q. (2025) Hyperbaric Oxygen Therapy Improves Motor Symptoms, Sleep, and Cognitive Dysfunctions in Parkinson’s Disease. Dementia and Geriatric Cognitive Disorders, 54, 187-200. [Google Scholar] [CrossRef] [PubMed]
[64] 周雯君, 林玮佳, 郑得忠. 移动智能认知训练联合重复经颅磁刺激对帕金森患者认知能力的影响[J]. 哈尔滨医药, 2026, 46(1): 82-84.

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