{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:19:38Z","timestamp":1790140778194,"version":"4.0.1"},"reference-count":229,"publisher":"IMR Press","issue":"5","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second most common degenerative disease of the central nervous system, characterized by both motor and non-motor disorders. Non-motor disorders include dementia, depression, and anxiety. The prevalence of dementia increases with disease progression, affecting 24\u201331% of PD patients and up to 75% after 10 years. Furthermore, approximately 50% of PD patients suffer from depression, while anxiety affects around 31% of this population. Molecular factors, including genetic factors, are currently implicated in the manifestation of neuropsychiatric disorders. It is believed that dementia and affective disorders in PD may result from both disturbed homeostasis of proteins such as \u03b1-synuclein, amyloid beta, and phosphorylated tau, as well as increased inflammatory processes and impaired neurotransmission. Chronic microglial activation, elevated levels of proinflammatory cytokines, and oxidative stress contribute to the severity of neuroinflammation, which in turn contributes to neuronal dysfunction and synaptic abnormalities. While the effect of pathological proteins in PD primarily involves impairment of dopaminergic neurotransmission, disturbances in the serotonergic, noradrenergic, cholinergic, and glutamatergic systems are also observed. Furthermore, genetic risk factors have been identified in PD patients, including monogenic causes, which are rare in unselected populations. Identifying causative molecular targets in PD is essential for developing therapies for this neurodegenerative disease. In this review, we present current views on the involvement of molecular factors in the development of psychiatric disorders in patients with PD, suggesting that they may have diagnostic and predictive value in the future.<\/jats:p>","DOI":"10.31083\/jin50055","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:26:51Z","timestamp":1780129611000},"source":"Crossref","is-referenced-by-count":1,"title":["Molecular Mechanisms and Potential Biomarkers of Neuropsychiatric Disorders in Parkinson\u2019s Disease"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9527-833X","authenticated-orcid":true,"given":"Wojciech","family":"Owecki","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Student Scientific Society, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Futyma","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Student Scientific Society, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kokorniak","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Student Scientific Society, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Szczech","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Student Scientific Society, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-486X","authenticated-orcid":true,"given":"Bartosz","family":"S\u0142owikowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4407-7014","authenticated-orcid":true,"given":"Joanna","family":"Poszwa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5326-6388","authenticated-orcid":true,"given":"Oliwia","family":"Szymanowicz","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2257-1594","authenticated-orcid":true,"given":"Ulyana","family":"Goutor","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-6802","authenticated-orcid":true,"given":"Pawe\u0142 P.","family":"Jagodzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2777-261X","authenticated-orcid":true,"given":"Wojciech","family":"Kozubski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-0403","authenticated-orcid":true,"given":"Jolanta","family":"Dorszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Jankovic J. Parkinson\u2019s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery, and Psychiatry. 2008; 79: 368\u2013376.","DOI":"10.1136\/jnnp.2007.131045"},{"key":"ref2","unstructured":"Kouli A, Torsney KM, Kuan WL. Parkinson\u2019s disease: Etiology, neuropathology, and pathogenesis. In Stoker TB, Greenland JC (eds.) Parkinson\u2019s Disease: Pathogenesis and Clinical Aspects. Codon Publications: Brisbane (AU). 2018."},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry. 1992; 55: 181\u2013184.","DOI":"10.1136\/jnnp.55.3.181"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Sveinbjornsdottir S. The clinical symptoms of Parkinson\u2019s disease. Journal of Neurochemistry. 2016; 139: 318\u2013324.","DOI":"10.1111\/jnc.13691"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Virmani T, Moskowitz CB, Vonsattel JP, Fahn S. Clinicopathological characteristics of freezing of gait in autopsy-confirmed Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2015; 30: 1874\u20131884.","DOI":"10.1002\/mds.26346"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Perez-Lloret S, N\u00e8gre-Pag\u00e8s L, Ojero-Senard A, Damier P, Dest\u00e9e A, Tison F, et al. Oro-buccal symptoms (dysphagia, dysarthria, and sialorrhea) in patients with Parkinson\u2019s disease: preliminary analysis from the French COPARK cohort. European Journal of Neurology. 2012; 19: 28\u201337.","DOI":"10.1111\/j.1468-1331.2011.03402.x"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Kalf JG, Borm GF, de Swart BJ, Bloem BR, Zwarts MJ, Munneke M. Reproducibility and validity of patient-rated assessment of speech, swallowing, and saliva control in Parkinson\u2019s disease. Archives of Physical Medicine and Rehabilitation. 2011; 92: 1152\u20131158.","DOI":"10.1016\/j.apmr.2011.02.011"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Jankovic J, Tintner R. Dystonia and parkinsonism. Parkinsonism & Related Disorders. 2001; 8: 109\u2013121.","DOI":"10.1016\/s1353-8020(01)00025-6"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Doherty KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik OS, et al. Postural deformities in Parkinson\u2019s disease. The Lancet. Neurology. 2011; 10: 538\u2013549.","DOI":"10.1016\/S1474-4422(11)70067-9"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Cury RG, Galhardoni R, Fonoff ET, Perez Lloret S, Dos Santos Ghilardi MG, Barbosa ER, et al. Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms. European Journal of Pain (London, England). 2016; 20: 151\u2013165.","DOI":"10.1002\/ejp.745"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Hawkes CH, Shephard BC, Daniel SE. Olfactory dysfunction in Parkinson\u2019s disease. Journal of Neurology, Neurosurgery, and Psychiatry. 1997; 62: 436\u2013446.","DOI":"10.1136\/jnnp.62.5.436"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Goetz CG, Lutge W, Tanner CM. Autonomic dysfunction in Parkinson\u2019s disease. Neurology. 1986; 36: 73\u201375.","DOI":"10.1212\/wnl.36.1.73"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Yu QJ, Yu SY, Zuo LJ, Lian TH, Hu Y, Wang RD, et al. Parkinson disease with constipation: clinical features and relevant factors. Scientific Reports. 2018; 8: 567.","DOI":"10.1038\/s41598-017-16790-8"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Shulman LM, Taback RL, Bean J, Weiner WJ. Comorbidity of the nonmotor symptoms of Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2001; 16: 507\u2013510.","DOI":"10.1002\/mds.1099"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Fang C, Lv L, Mao S, Dong H, Liu B. Cognition Deficits in Parkinson\u2019s Disease: Mechanisms and Treatment. Parkinson\u2019s Disease. 2020; 2020: 2076942.","DOI":"10.1155\/2020\/2076942"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"F\u00e9nelon G, Mahieux F, Huon R, Zi\u00e9gler M. Hallucinations in Parkinson\u2019s disease: prevalence, phenomenology and risk factors. Brain: a Journal of Neurology. 2000; 123 ( Pt 4): 733\u2013745.","DOI":"10.1093\/brain\/123.4.733"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Tandberg E, Larsen JP, Karlsen K. A community-based study of sleep disorders in patients with Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 1998; 13: 895\u2013899.","DOI":"10.1002\/mds.870130606"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Reich SG, Savitt JM. Parkinson\u2019s Disease. The Medical Clinics of North America. 2019; 103: 337\u2013350.","DOI":"10.1016\/j.mcna.2018.10.014"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Witjas T, Kaphan E, Azulay JP, Blin O, Ceccaldi M, Pouget J, et al. Nonmotor fluctuations in Parkinson\u2019s disease: frequent and disabling. Neurology. 2002; 59: 408\u2013413.","DOI":"10.1212\/wnl.59.3.408"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Rohde C, Langeskov-Christensen M, J\u00f8rgensen LB, Borghammer P, \u00d8stergaard SD. Depression preceding and following the diagnosis of Parkinson\u2019s disease and Lewy body dementia. General Psychiatry. 2025; 38: e102405.","DOI":"10.1136\/gpsych-2025-102405"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Dujardin K, Sgambato V. Neuropsychiatric Disorders in Parkinson\u2019s Disease: What Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems? Frontiers in Neuroscience. 2020; 14: 25.","DOI":"10.3389\/fnins.2020.00025"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Dong-Chen X, Yong C, Yang X, Chen-Yu S, Li-Hua P. Signaling pathways in Parkinson\u2019s disease: molecular mechanisms and therapeutic interventions. Signal Transduction and Targeted Therapy. 2023; 8: 73.","DOI":"10.1038\/s41392-023-01353-3"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Maiti P, Manna J, Dunbar GL. Current understanding of the molecular mechanisms in Parkinson\u2019s disease: Targets for potential treatments. Translational Neurodegeneration. 2017; 6: 28.","DOI":"10.1186\/s40035-017-0099-z"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Kalia LV, Brotchie JM, Fox SH. Novel nondopaminergic targets for motor features of Parkinson\u2019s disease: review of recent trials. Movement Disorders: Official Journal of the Movement Disorder Society. 2013; 28: 131\u2013144.","DOI":"10.1002\/mds.25273"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"\u00c7\u0131nar E, Tel BC, \u015eahin G. Neuroinflammation in Parkinson\u2019s Disease and its Treatment Opportunities. Balkan Medical Journal. 2022; 39: 318\u2013333.","DOI":"10.4274\/balkanmedj.galenos.2022.2022-7-100"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Maitre M, Jeltsch-David H, Okechukwu NG, Klein C, Patte-Mensah C, Mensah-Nyagan AG. Myelin in Alzheimer\u2019s disease: culprit or bystander? Acta Neuropathologica Communications. 2023; 11: 56.","DOI":"10.1186\/s40478-023-01554-5"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Hall S, Janelidze S, Surova Y, Widner H, Zetterberg H, Hansson O. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson\u2019s disease and atypical parkinsonian disorders. Scientific Reports. 2018; 8: 13276.","DOI":"10.1038\/s41598-018-31517-z"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Villa C, Lavitrano M, Salvatore E, Combi R. Molecular and Imaging Biomarkers in Alzheimer\u2019s Disease: A Focus on Recent Insights. Journal of Personalized Medicine. 2020; 10: 61.","DOI":"10.3390\/jpm10030061"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Trinh J, Farrer M. Advances in the genetics of Parkinson disease. Nature Reviews. Neurology. 2013; 9: 445\u2013454.","DOI":"10.1038\/nrneurol.2013.132"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Ak\u00e7imen F, Paquette K, Crea PW, Saffie-Awad P, Achoru C, Taiwo F, et al. Large-scale genetic characterization of Parkinson\u2019s disease in the African and African admixed populations. medRxiv. 2025.  (preprint)","DOI":"10.1101\/2025.01.14.25320205"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Ye H, Robak LA, Yu M, Cykowski M, Shulman JM. Genetics and Pathogenesis of Parkinson\u2019s Syndrome. Annual Review of Pathology. 2023; 18: 95\u2013121.","DOI":"10.1146\/annurev-pathmechdis-031521-034145"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Golden TR, Patel M. Catalytic antioxidants and neurodegeneration. Antioxidants & Redox Signaling. 2009; 11: 555\u2013570.","DOI":"10.1089\/ars.2008.2256"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Tan JMM, Wong ESP, Lim KL. Protein misfolding and aggregation in Parkinson\u2019s disease. Antioxidants & Redox Signaling. 2009; 11: 2119\u20132134.","DOI":"10.1089\/ars.2009.2490"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Frouni I, Kwan C, Belliveau S, Huot P. Cognition and serotonin in Parkinson\u2019s disease. Progress in Brain Research. 2022; 269: 373\u2013403.","DOI":"10.1016\/bs.pbr.2022.01.013"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, et al. Cognitive decline in Parkinson disease. Nature Reviews. Neurology. 2017; 13: 217\u2013231.","DOI":"10.1038\/nrneurol.2017.27"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Myers PS, O\u2019Donnell JL, Jackson JJ, Lessov-Schlaggar CN, Miller RL, Foster ER, et al. Proteinopathy and Longitudinal Cognitive Decline in Parkinson Disease. Neurology. 2022; 99: e66\u2013e76.","DOI":"10.1212\/WNL.0000000000200344"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson\u2019s disease. Lancet (London, England). 2024; 403: 293\u2013304.","DOI":"10.1016\/S0140-6736(23)01478-2"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"S\u0142owikowski B, Owecki W, Jeske J, Jezierski M, Dragu\u0142a M, Goutor U, et al. Epigenetics and the neurodegenerative process. Epigenomics. 2024; 16: 473\u2013491.","DOI":"10.2217\/epi-2023-0416"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Irwin DJ, Lee VMY, Trojanowski JQ. Parkinson\u2019s disease dementia: convergence of \u03b1-synuclein, tau and amyloid-\u03b2 pathologies. Nature Reviews. Neuroscience. 2013; 14: 626\u2013636.","DOI":"10.1038\/nrn3549"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Rom\u00e1n-Vendrell C, Medeiros AT, Sanderson JB, Jiang H, Bartels T, Morgan JR. Effects of Excess Brain-Derived Human \u03b1-Synuclein on Synaptic Vesicle Trafficking. Frontiers in Neuroscience. 2021; 15: 639414.","DOI":"10.3389\/fnins.2021.639414"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"O\u2019Leary EI, Lee JC. Interplay between \u03b1-synuclein amyloid formation and membrane structure. Biochimica et Biophysica Acta. Proteins and Proteomics. 2019; 1867: 483\u2013491.","DOI":"10.1016\/j.bbapap.2018.09.012"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Fan TS, Liu SCH, Wu RM. Alpha-Synuclein and Cognitive Decline in Parkinson Disease. Life (Basel, Switzerland). 2021; 11: 1239.","DOI":"10.3390\/life11111239"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Lin CH, Yang SY, Horng HE, Yang CC, Chieh JJ, Chen HH, et al. Plasma \u03b1-synuclein predicts cognitive decline in Parkinson\u2019s disease. Journal of Neurology, Neurosurgery, and Psychiatry. 2017; 88: 818\u2013824.","DOI":"10.1136\/jnnp-2016-314857"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Stewart T, Liu C, Ginghina C, Cain KC, Auinger P, Cholerton B, et al. Cerebrospinal fluid \u03b1-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort. The American Journal of Pathology. 2014; 184: 966\u2013975.","DOI":"10.1016\/j.ajpath.2013.12.007"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Kouli A, Camacho M, Allinson K, Williams-Gray CH. Neuroinflammation and protein pathology in Parkinson\u2019s disease dementia. Acta Neuropathologica Communications. 2020; 8: 211.","DOI":"10.1186\/s40478-020-01083-5"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Zhu Z, Cordato D, Chen R, Xu YH, Shulruf B, Chan DKY. Plasma alpha-synuclein predicts cognitive impairment in Parkinson\u2019s disease: a systematic review and meta-analysis. Journal of Neurology. 2025; 272: 124.","DOI":"10.1007\/s00415-024-12871-7"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Uemura N, Ueda J, Yoshihara T, Ikuno M, Uemura MT, Yamakado H, et al. \u03b1-Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in BAC-SNCA Mice. Movement Disorders: Official Journal of the Movement Disorder Society. 2021; 36: 2036\u20132047.","DOI":"10.1002\/mds.28512"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Weber MA, Kerr G, Thangavel R, Conlon MM, Gumusoglu SB, Gupta K, et al. Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures. Journal of Parkinson\u2019s Disease. 2024; 14: 81\u201394.","DOI":"10.3233\/JPD-230129"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Boutros SW, Raber J, Unni VK. Effects of Alpha-Synuclein Targeted Antisense Oligonucleotides on Lewy Body-Like Pathology and Behavioral Disturbances Induced by Injections of Pre-Formed Fibrils in the Mouse Motor Cortex. Journal of Parkinson\u2019s Disease. 2021; 11: 1091\u20131115.","DOI":"10.3233\/JPD-212566"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Kim J, Ghadery C, Cho SS, Mihaescu A, Christopher L, Valli M, et al. Network Patterns of Beta-Amyloid Deposition in Parkinson\u2019s Disease. Molecular Neurobiology. 2019; 56: 7731\u20137740.","DOI":"10.1007\/s12035-019-1625-z"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Melzer TR, Stark MR, Keenan RJ, Myall DJ, MacAskill MR, Pitcher TL, et al. Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson\u2019s Disease. Frontiers in Neurology. 2019; 10: 391.","DOI":"10.3389\/fneur.2019.00391"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Burack MA, Hartlein J, Flores HP, Taylor-Reinwald L, Perlmutter JS, Cairns NJ. In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology. 2010; 74: 77\u201384.","DOI":"10.1212\/WNL.0b013e3181c7da8e"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Akhtar RS, Xie SX, Chen YJ, Rick J, Gross RG, Nasrallah IM, et al. Regional brain amyloid-\u03b2 accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia. PloS One. 2017; 12: e0177924.","DOI":"10.1371\/journal.pone.0177924"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Mihaescu AS, Valli M, Uribe C, Diez-Cirarda M, Masellis M, Graff-Guerrero A, et al. Beta amyloid deposition and cognitive decline in Parkinson\u2019s disease: a study of the PPMI cohort. Molecular Brain. 2022; 15: 79.","DOI":"10.1186\/s13041-022-00964-1"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Edison P, Ahmed I, Fan Z, Hinz R, Gelosa G, Ray Chaudhuri K, et al. Microglia, amyloid, and glucose metabolism in Parkinson\u2019s disease with and without dementia. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 2013; 38: 938\u2013949.","DOI":"10.1038\/npp.2012.255"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Chen L, Lu H, Mao L, Lin J, Liu P. Unraveling the interplay of \u03b2-amyloid pathology and Parkinson\u2019s disease progression: Insights from autopsy-confirmed patients. Heliyon. 2024; 10: e39194.","DOI":"10.1016\/j.heliyon.2024.e39194"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Mashima K, Ito D, Kameyama M, Osada T, Tabuchi H, Nihei Y, et al. Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson\u2019s Disease without Dementia. European Neurology. 2017; 77: 231\u2013237.","DOI":"10.1159\/000464322"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Winer JR, Maass A, Pressman P, Stiver J, Schonhaut DR, Baker SL, et al. Associations Between Tau, \u03b2-Amyloid, and Cognition in Parkinson Disease. JAMA Neurology. 2018; 75: 227\u2013235.","DOI":"10.1001\/jamaneurol.2017.3713"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Kotzbauer PT, Cairns NJ, Campbell MC, Willis AW, Racette BA, Tabbal SD, et al. Pathologic accumulation of \u03b1-synuclein and A\u03b2 in Parkinson disease patients with dementia. Archives of Neurology. 2012; 69: 1326\u20131331.","DOI":"10.1001\/archneurol.2012.1608"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Tresse E, Marturia-Navarro J, Sew WQG, Cisquella-Serra M, Jaberi E, Riera-Ponsati L, et al. Mitochondrial DNA damage triggers spread of Parkinson\u2019s disease-like pathology. Molecular Psychiatry. 2023; 28: 4902\u20134914.","DOI":"10.1038\/s41380-023-02251-4"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Villanueva EB, Tresse E, Liu Y, Duarte JN, Jimenez-Duran G, Ejlerskov P, et al. Neuronal TNF\u03b1, Not \u03b1-Syn, Underlies PDD-Like Disease Progression in IFN\u03b2-KO Mice. Annals of Neurology. 2021; 90: 789\u2013807.","DOI":"10.1002\/ana.26209"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Ghadery C, Koshimori Y, Christopher L, Kim J, Rusjan P, Lang AE, et al. The Interaction Between Neuroinflammation and \u03b2-Amyloid in Cognitive Decline in Parkinson\u2019s Disease. Molecular Neurobiology. 2020; 57: 492\u2013501.","DOI":"10.1007\/s12035-019-01714-6"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Fan Z, Aman Y, Ahmed I, Chetelat G, Landeau B, Ray Chaudhuri K, et al. Influence of microglial activation on neuronal function in Alzheimer\u2019s and Parkinson\u2019s disease dementia. Alzheimer\u2019s & Dementia: the Journal of the Alzheimer\u2019s Association. 2015; 11: 608\u2013621.e7.","DOI":"10.1016\/j.jalz.2014.06.016"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Thangavel R, Kaur H, Dubova I, Selvakumar GP, Ahmed ME, Raikwar SP, et al. Parkinson\u2019s Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain. International Journal of Molecular Sciences. 2024; 25: 1182.","DOI":"10.3390\/ijms25021182"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Kouli A, Spindler LRB, Fryer TD, Hong YT, Malpetti M, Aigbirhio FI, et al. Neuroinflammation is linked to dementia risk in Parkinson\u2019s disease. Brain: a Journal of Neurology. 2024; 147: 923\u2013935.","DOI":"10.1093\/brain\/awad322"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Chai YL, Lee JH, Chong JR, Ballard C, Francis PT, Kennedy BK, et al. Inflammatory panel cytokines are elevated in the neocortex of late-stage Alzheimer\u2019s disease but not Lewy body dementias. Journal of Neuroinflammation. 2023; 20: 111.","DOI":"10.1186\/s12974-023-02789-8"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Scorziello A, Sirabella R, Sisalli MJ, Tufano M, Giaccio L, D\u2019Apolito E, et al. Mitochondrial Dysfunction in Parkinson\u2019s Disease: A Contribution to Cognitive Impairment? International Journal of Molecular Sciences. 2024; 25: 11490.","DOI":"10.3390\/ijms252111490"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Gatt AP, Duncan OF, Attems J, Francis PT, Ballard CG, Bateman JM. Dementia in Parkinson\u2019s disease is associated with enhanced mitochondrial complex I deficiency. Movement Disorders: Official Journal of the Movement Disorder Society. 2016; 31: 352\u2013359.","DOI":"10.1002\/mds.26513"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Garcia-Esparcia P, Koneti A, Rodr\u00edguez-Oroz MC, Gago B, Del Rio JA, Ferrer I. Mitochondrial activity in the frontal cortex area 8 and angular gyrus in Parkinson\u2019s disease and Parkinson\u2019s disease with dementia. Brain Pathology (Zurich, Switzerland). 2018; 28: 43\u201357.","DOI":"10.1111\/bpa.12474"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"Magalhaes J, Tresse E, Ejlerskov P, Hu E, Liu Y, Marin A, et al. PIAS2-mediated blockade of IFN-\u03b2 signaling: a basis for sporadic Parkinson disease dementia. Molecular Psychiatry. 2021; 26: 6083\u20136099.","DOI":"10.1038\/s41380-021-01207-w"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"Calabresi P, Di Lazzaro G, Marino G, Campanelli F, Ghiglieri V. Advances in understanding the function of alpha-synuclein: implications for Parkinson\u2019s disease. Brain: a Journal of Neurology. 2023; 146: 3587\u20133597.","DOI":"10.1093\/brain\/awad150"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Gonzalez-Latapi P, Bayram E, Litvan I, Marras C. Cognitive Impairment in Parkinson\u2019s Disease: Epidemiology, Clinical Profile, Protective and Risk Factors. Behavioral Sciences (Basel, Switzerland). 2021; 11: 74.","DOI":"10.3390\/bs11050074"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"Kehagia AA, Barker RA, Robbins TW. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson\u2019s disease. The Lancet. Neurology. 2010; 9: 1200\u20131213.","DOI":"10.1016\/S1474-4422(10)70212-X"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"Gratwicke J, Jahanshahi M, Foltynie T. Parkinson\u2019s disease dementia: a neural networks perspective. Brain: a Journal of Neurology. 2015; 138: 1454\u20131476.","DOI":"10.1093\/brain\/awv104"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Klein JC, Eggers C, Kalbe E, Weisenbach S, Hohmann C, Vollmar S, et al. Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo. Neurology. 2010; 74: 885\u2013892.","DOI":"10.1212\/WNL.0b013e3181d55f61"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Hilker R, Thomas AV, Klein JC, Weisenbach S, Kalbe E, Burghaus L, et al. Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways. Neurology. 2005; 65: 1716\u20131722.","DOI":"10.1212\/01.wnl.0000191154.78131.f6"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Tiraboschi P, Hansen LA, Alford M, Sabbagh MN, Schoos B, Masliah E, et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology. 2000; 54: 407\u2013411.","DOI":"10.1212\/wnl.54.2.407"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Ziabreva I, Ballard CG, Aarsland D, Larsen JP, McKeith IG, Perry RH, et al. Lewy body disease: thalamic cholinergic activity related to dementia and parkinsonism. Neurobiology of Aging. 2006; 27: 433\u2013438.","DOI":"10.1016\/j.neurobiolaging.2005.02.004"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Colloby SJ, Pakrasi S, Firbank MJ, Perry EK, Piggott MA, Owens J, et al. In vivo SPECT imaging of muscarinic acetylcholine receptors using (R,R) 123I-QNB in dementia with Lewy bodies and Parkinson\u2019s disease dementia. NeuroImage. 2006; 33: 423\u2013429.","DOI":"10.1016\/j.neuroimage.2006.07.026"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"Zgaljardic DJ, Foldi NS, Borod JC. Cognitive and behavioral dysfunction in Parkinson\u2019s disease: neurochemical and clinicopathological contributions. Journal of Neural Transmission (Vienna, Austria: 1996). 2004; 111: 1287\u20131301.","DOI":"10.1007\/s00702-004-0178-z"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"Halliday GM, Leverenz JB, Schneider JS, Adler CH. The neurobiological basis of cognitive impairment in Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2014; 29: 634\u2013650.","DOI":"10.1002\/mds.25857"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"van der Zee S, Vermeiren Y, Fransen E, Van Dam D, Aerts T, Gerritsen MJ, et al. Monoaminergic Markers Across the Cognitive Spectrum of Lewy Body Disease. Journal of Parkinson\u2019s Disease. 2018; 8: 71\u201384.","DOI":"10.3233\/JPD-171228"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Kozubski W, Ong K, Waleszczyk W, Zabel M, Dorszewska J. Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases. Neural Plasticity. 2021; 2021: 8834645.","DOI":"10.1155\/2021\/8834645"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson\u2019s disease and Parkinson\u2019s disease dementia. Acta Neuropathologica. 2010; 120: 131\u2013143.","DOI":"10.1007\/s00401-010-0711-0"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Dorszewska J, Kozubski W, Waleszczyk W, Zabel M, Ong K. Neuroplasticity in the Pathology of Neurodegenerative Diseases. Neural Plasticity. 2020; 2020: 4245821.","DOI":"10.1155\/2020\/4245821"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"G\u00f3mez-Palacio-Schjetnan A, Escobar ML. Neurotrophins and synaptic plasticity. Current Topics in Behavioral Neurosciences. 2013; 15: 117\u2013136.","DOI":"10.1007\/7854_2012_231"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Bia\u0142ecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, et al. BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson\u2019s disease. Neuroscience Letters. 2014; 561: 86\u201390.","DOI":"10.1016\/j.neulet.2013.12.051"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Wang Q, Liu J, Guo Y, Dong G, Zou W, Chen Z. Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson\u2019s disease: a meta-analysis. Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas. 2019; 52: e8443.","DOI":"10.1590\/1414-431X20198443"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Lim NS, Swanson CR, Cherng HR, Unger TL, Xie SX, Weintraub D, et al. Plasma EGF and cognitive decline in Parkinson\u2019s disease and Alzheimer\u2019s disease. Annals of Clinical and Translational Neurology. 2016; 3: 346\u2013355.","DOI":"10.1002\/acn3.299"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"Hu M, Ye J. Clinical efficacy of donepezil combined with nerve growth factor in the treatment of patients with Parkinson\u2019s disease dementia and its impact on adiponectin and soluble tumor necrosis factor-alpha receptor-1. Pakistan Journal of Medical Sciences. 2025; 41: 372\u2013377.","DOI":"10.12669\/pjms.41.2.11191"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Bereczki E, Francis PT, Howlett D, Pereira JB, H\u00f6glund K, Bogstedt A, et al. Synaptic proteins predict cognitive decline in Alzheimer\u2019s disease and Lewy body dementia. Alzheimer\u2019s & Dementia: the Journal of the Alzheimer\u2019s Association. 2016; 12: 1149\u20131158.","DOI":"10.1016\/j.jalz.2016.04.005"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"Whitfield DR, Vallortigara J, Alghamdi A, Howlett D, Hortob\u00e1gyi T, Johnson M, et al. Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer\u2019s disease: association with cognitive impairment. Neurobiology of Aging. 2014; 35: 2836\u20132844.","DOI":"10.1016\/j.neurobiolaging.2014.06.015"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Datta A, Chai YL, Tan JM, Lee JH, Francis PT, Chen CP, et al. An iTRAQ-based proteomic analysis reveals dysregulation of neocortical synaptopodin in Lewy body dementias. Molecular Brain. 2017; 10: 36.","DOI":"10.1186\/s13041-017-0316-9"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Vallortigara J, Rangarajan S, Whitfield D, Alghamdi A, Howlett D, Hortob\u00e1gyi T, et al. Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia. F1000Research. 2014; 3: 108.","DOI":"10.12688\/f1000research.3786.1"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Stocchi F, Angelo Antonini, Barone P, Bellelli G, Fagiolini A, Ferini Strambi L, et al. Exploring depression in Parkinson\u2019s disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2023; 44: 3123\u20133131.","DOI":"10.1007\/s10072-023-06740-w"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Allain H, Schuck S, Mauduit N. Depression in Parkinson\u2019s disease. BMJ (Clinical Research Ed.). 2000; 320: 1287\u20131288.","DOI":"10.1136\/bmj.320.7245.1287"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, et al. The neuropsychiatry of Parkinson\u2019s disease: advances and challenges. The Lancet. Neurology. 2022; 21: 89\u2013102.","DOI":"10.1016\/S1474-4422(21)00330-6"},{"key":"ref98","doi-asserted-by":"publisher","unstructured":"Ahmad MH, Rizvi MA, Ali M, Mondal AC. Neurobiology of depression in Parkinson\u2019s disease: Insights into epidemiology, molecular mechanisms and treatment strategies. Ageing Research Reviews. 2023; 85: 101840.","DOI":"10.1016\/j.arr.2022.101840"},{"key":"ref99","doi-asserted-by":"publisher","unstructured":"Zhang P, Jin W, Lyu Z, Lyu X, Li L. Study on the mechanism of gut microbiota in the pathogenetic interaction between depression and Parkinson \u2019s disease. Brain Research Bulletin. 2024; 215: 111001.","DOI":"10.1016\/j.brainresbull.2024.111001"},{"key":"ref100","doi-asserted-by":"publisher","unstructured":"Sarri\u00e9s-Serrano U, Miquel-Rio L, Santana N, Paz V, Sancho-Alonso M, Callado LF, et al. Impaired unfolded protein response, BDNF and synuclein markers in postmortem dorsolateral prefrontal cortex and caudate nucleus of patients with depression and Parkinson\u2019s disease. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2025; 138: 111299.","DOI":"10.1016\/j.pnpbp.2025.111299"},{"key":"ref101","doi-asserted-by":"publisher","unstructured":"Miquel-Rio L, Alarc\u00f3n-Ar\u00eds D, Torres-L\u00f3pez M, C\u00f3ppola-Segovia V, Pavia-Collado R, Paz V, et al. Human \u03b1-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy. Translational Psychiatry. 2022; 12: 79.","DOI":"10.1038\/s41398-022-01842-z"},{"key":"ref102","doi-asserted-by":"publisher","unstructured":"Yusuf AM, Ilce BY, Alhaj HA, Hamoudi R. \u03b1-synuclein in Parkinson\u2019s disease: a central point of convergence with depression. NPJ Parkinson\u2019s Disease. 2025; 11: 329.","DOI":"10.1038\/s41531-025-01167-w"},{"key":"ref103","doi-asserted-by":"publisher","unstructured":"Lindqvist D, Hall S, Surova Y, Nielsen HM, Janelidze S, Brundin L, et al. Cerebrospinal fluid inflammatory markers in Parkinson\u2019s disease\u2013associations with depression, fatigue, and cognitive impairment. Brain, Behavior, and Immunity. 2013; 33: 183\u2013189.","DOI":"10.1016\/j.bbi.2013.07.007"},{"key":"ref104","doi-asserted-by":"publisher","unstructured":"Prange S, Klinger H, Laurencin C, Danaila T, Thobois S. Depression in Patients with Parkinson\u2019s Disease: Current Understanding of its Neurobiology and Implications for Treatment. Drugs & Aging. 2022; 39: 417\u2013439.","DOI":"10.1007\/s40266-022-00942-1"},{"key":"ref105","doi-asserted-by":"publisher","unstructured":"Yang D, Chen F, Ren J, Wang L, Zhu Z, Wu Z, et al. Longitudinal associations between cerebrospinal fluid glial activation markers, depression, and dopamine transporter availability in patients with Parkinson\u2019s disease. Journal of Neurology. 2024; 272: 23.","DOI":"10.1007\/s00415-024-12779-2"},{"key":"ref106","doi-asserted-by":"publisher","unstructured":"Mendon\u00e7a IP, Paiva IHRD, Duarte-Silva EP, Melo MGD, Silva RSD, Oliveira WHD, et al. Metformin and fluoxetine improve depressive-like behavior in a murine model of Parkinso\u0144s disease through the modulation of neuroinflammation, neurogenesis and neuroplasticity. International Immunopharmacology. 2022; 102: 108415.","DOI":"10.1016\/j.intimp.2021.108415"},{"key":"ref107","doi-asserted-by":"publisher","unstructured":"Zhang J, Zhang N, Lei J, Jing B, Li M, Tian H, et al. Fluoxetine shows neuroprotective effects against LPS-induced neuroinflammation via the Notch signaling pathway. International Immunopharmacology. 2022; 113: 109417.","DOI":"10.1016\/j.intimp.2022.109417"},{"key":"ref108","doi-asserted-by":"publisher","unstructured":"Liu X, Chen W, Wang C, Liu W, Hayashi T, Mizuno K, et al. Silibinin ameliorates depression\/anxiety-like behaviors of Parkinson\u2019s disease mouse model and is associated with attenuated STING-IRF3-IFN-\u03b2 pathway activation and neuroinflammation. Physiology & Behavior. 2021; 241: 113593.","DOI":"10.1016\/j.physbeh.2021.113593"},{"key":"ref109","doi-asserted-by":"publisher","unstructured":"Christopoulos PF, Gj\u00f8lberg TT, Kr\u00fcger S, Haraldsen G, Andersen JT, Sundlis\u00e6ter E. Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases. Frontiers in Immunology. 2021; 12: 668207.","DOI":"10.3389\/fimmu.2021.668207"},{"key":"ref110","doi-asserted-by":"publisher","unstructured":"Ren C, Li LX, Dong AQ, Zhang YT, Hu H, Mao CJ, et al. Depression Induced by Chronic Unpredictable Mild Stress Increases Susceptibility to Parkinson\u2019s Disease in Mice via Neuroinflammation Mediated by P2X7 Receptor. ACS Chemical Neuroscience. 2021; 12: 1262\u20131272.","DOI":"10.1021\/acschemneuro.1c00095"},{"key":"ref111","doi-asserted-by":"publisher","unstructured":"Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Bienfait K, et al. The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson\u2019s disease. Psychosomatics. 2010; 51: 474\u2013479.","DOI":"10.1176\/appi.psy.51.6.474"},{"key":"ref112","doi-asserted-by":"publisher","unstructured":"Bonato JM, Bassani TB, Milani H, Vital MABF, de Oliveira RMW. Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson\u2019s disease in rats. Experimental Neurology. 2018; 300: 188\u2013200.","DOI":"10.1016\/j.expneurol.2017.11.009"},{"key":"ref113","doi-asserted-by":"publisher","unstructured":"Mendon\u00e7a IP, Duarte-Silva E, Chaves-Filho AJM, Andrade da Costa BLDS, Peixoto CA. Neurobiological findings underlying depressive behavior in Parkinson\u2019s disease: A review. International Immunopharmacology. 2020; 83: 106434.","DOI":"10.1016\/j.intimp.2020.106434"},{"key":"ref114","doi-asserted-by":"publisher","unstructured":"Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson\u2019s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain: a Journal of Neurology. 2005; 128: 1314\u20131322.","DOI":"10.1093\/brain\/awh445"},{"key":"ref115","doi-asserted-by":"publisher","unstructured":"Hui Y, Du C, Xu T, Zhang Q, Tan H, Liu J. Dopamine D4 receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson\u2019s disease. Neurochemistry International. 2020; 140: 104844.","DOI":"10.1016\/j.neuint.2020.104844"},{"key":"ref116","doi-asserted-by":"publisher","unstructured":"Felicio AC, Moriyama TS, Godeiro-Junior C, Shih MC, Hoexter MQ, Borges V, et al. Higher dopamine transporter density in Parkinson\u2019s disease patients with depression. Psychopharmacology (Berl). 2010; 211: 27\u201331.","DOI":"10.1007\/s00213-010-1867-y"},{"key":"ref117","unstructured":"Weintraub D, Newberg AB, Cary MS, Siderowf AD, Moberg PJ, Kleiner-Fisman G, et al. Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson\u2019s disease. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine. 2005; 46: 227\u2013232."},{"key":"ref118","doi-asserted-by":"publisher","unstructured":"Yoo SW, Oh YS, Hwang EJ, Ryu DW, Lee KS, Lyoo CH, et al. \u201cDepressed\u201d caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson\u2019s disease. Neurobiology of Disease. 2019; 132: 104563.","DOI":"10.1016\/j.nbd.2019.104563"},{"key":"ref119","doi-asserted-by":"publisher","unstructured":"Rektorova I, Srovnalova H, Kubikova R, Prasek J. Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2008; 23: 1580\u20131587.","DOI":"10.1002\/mds.22158"},{"key":"ref120","doi-asserted-by":"publisher","unstructured":"Jellinger KA. The pathobiological basis of depression in Parkinson disease: challenges and outlooks. Journal of Neural Transmission (Vienna, Austria: 1996). 2022; 129: 1397\u20131418.","DOI":"10.1007\/s00702-022-02559-5"},{"key":"ref121","doi-asserted-by":"publisher","unstructured":"Vriend C, Raijmakers P, Veltman DJ, van Dijk KD, van der Werf YD, Foncke EM, et al. Depressive symptoms in Parkinson\u2019s disease are related to reduced [123I]FP-CIT binding in the caudate nucleus. Journal of Neurology, Neurosurgery and Psychiatry. 2014; 85: 159\u2013164.","DOI":"10.1136\/jnnp-2012-304811"},{"key":"ref122","doi-asserted-by":"publisher","unstructured":"Maillet A, Krack P, Lhomm\u00e9e E, M\u00e9t\u00e9reau E, Klinger H, Favre E, et al. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson\u2019s disease. Brain. 2016; 139: 2486\u20132502.","DOI":"10.1093\/brain\/aww162"},{"key":"ref123","doi-asserted-by":"publisher","unstructured":"Pagano G, Politis M. Molecular Imaging of the Serotonergic System in Parkinson\u2019s Disease. International Review of Neurobiology. 2018; 141: 173\u2013210.","DOI":"10.1016\/bs.irn.2018.08.002"},{"key":"ref124","doi-asserted-by":"publisher","unstructured":"Pasquini J, Ceravolo R, Brooks DJ, Bonuccelli U, Pavese N. Progressive loss of raphe nuclei serotonin transporter in early Parkinson\u2019s disease: A longitudinal 123I-FP-CIT SPECT study. Parkinsonism & Related Disorders. 2020; 77: 170\u2013175.","DOI":"10.1016\/j.parkreldis.2019.03.025"},{"key":"ref125","doi-asserted-by":"publisher","unstructured":"Pagano G, Niccolini F, Fusar-Poli P, Politis M. Serotonin transporter in Parkinson\u2019s disease: A meta-analysis of positron emission tomography studies. Annals of Neurology. 2017; 81: 171\u2013180.","DOI":"10.1002\/ana.24859"},{"key":"ref126","doi-asserted-by":"publisher","unstructured":"Fazio P, Ferreira D, Svenningsson P, Halldin C, Farde L, Westman E, et al. High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson\u2019s disease cohort. European Journal of Nuclear Medicine and Molecular Imaging. 2020; 47: 2407\u20132416.","DOI":"10.1007\/s00259-020-04683-4"},{"key":"ref127","doi-asserted-by":"publisher","unstructured":"Politis M, Wu K, Loane C, Turkheimer FE, Molloy S, Brooks DJ, et al. Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures. Neurology. 2010; 75: 1920\u20131927.","DOI":"10.1212\/WNL.0b013e3181feb2ab"},{"key":"ref128","doi-asserted-by":"publisher","unstructured":"Sharp SI, Ballard CG, Ziabreva I, Piggott MA, Perry RH, Perry EK, et al. Cortical serotonin 1A receptor levels are associated with depression in patients with dementia with Lewy bodies and Parkinson\u2019s disease dementia. Dementia and Geriatric Cognitive Disorders. 2008; 26: 330\u2013338.","DOI":"10.1159\/000161058"},{"key":"ref129","doi-asserted-by":"publisher","unstructured":"Bohnen NI, Yarnall AJ, Weil RS, Moro E, Moehle MS, Borghammer P, et al. Cholinergic system changes in Parkinson\u2019s disease: emerging therapeutic approaches. The Lancet. Neurology. 2022; 21: 381\u2013392.","DOI":"10.1016\/S1474-4422(21)00377-X"},{"key":"ref130","doi-asserted-by":"publisher","unstructured":"Albin RL, van der Zee S, van Laar T, Sarter M, Lustig C, Muller MLTM, et al. Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson\u2019s disease. Progress in Brain Research. 2022; 269: 345\u2013371.","DOI":"10.1016\/bs.pbr.2022.01.011"},{"key":"ref131","doi-asserted-by":"publisher","unstructured":"Bohnen NI, Kaufer DI, Hendrickson R, Constantine GM, Mathis CA, Moore RY. Cortical cholinergic denervation is associated with depressive symptoms in Parkinson\u2019s disease and parkinsonian dementia. Journal of Neurology, Neurosurgery, and Psychiatry. 2007; 78: 641\u2013643.","DOI":"10.1136\/jnnp.2006.100073"},{"key":"ref132","doi-asserted-by":"publisher","unstructured":"Schwarz LA, Luo L. Organization of the locus coeruleus-norepinephrine system. Current Biology: CB. 2015; 25: R1051\u2013R1056.","DOI":"10.1016\/j.cub.2015.09.039"},{"key":"ref133","doi-asserted-by":"publisher","unstructured":"Liu X, Li Y, Mo Y, Chen B, Hou X, Zhu J, et al. GABAergic imbalance in Parkinson\u2019s disease-related depression determined with MEGA-PRESS. NeuroImage. Clinical. 2024; 43: 103641.","DOI":"10.1016\/j.nicl.2024.103641"},{"key":"ref134","doi-asserted-by":"publisher","unstructured":"Wang Y, Bai LP, Liu W, Zhu XD, Zhang XY. Altered BDNF levels are associated with cognitive impairment in Parkinson\u2019s disease patients with depression. Parkinsonism & Related Disorders. 2022; 103: 122\u2013128.","DOI":"10.1016\/j.parkreldis.2022.08.020"},{"key":"ref135","doi-asserted-by":"publisher","unstructured":"Huang Y, Huang C, Zhang Q, Wu W, Sun J. Serum BDNF discriminates Parkinson\u2019s disease patients with depression from without depression and reflect motor severity and gender differences. Journal of Neurology. 2021; 268: 1411\u20131418.","DOI":"10.1007\/s00415-020-10299-3"},{"key":"ref136","doi-asserted-by":"publisher","unstructured":"Wang Y, Liu H, Du XD, Zhang Y, Yin G, Zhang BS, et al. Association of low serum BDNF with depression in patients with Parkinson\u2019s disease. Parkinsonism & Related Disorders. 2017; 41: 73\u201378.","DOI":"10.1016\/j.parkreldis.2017.05.012"},{"key":"ref137","doi-asserted-by":"publisher","unstructured":"Zhao X, Kong D, Zhou Q, Wei G, Song J, Liang Y, et al. Baicalein alleviates depression-like behavior in rotenone- induced Parkinson\u2019s disease model in mice through activating the BDNF\/TrkB\/CREB pathway. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2021; 140: 111556.","DOI":"10.1016\/j.biopha.2021.111556"},{"key":"ref138","doi-asserted-by":"publisher","unstructured":"Rahmani F, Saghazadeh A, Rahmani M, Teixeira AL, Rezaei N, Aghamollaii V, et al. Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: A systematic review and meta-analysis. Brain Research. 2019; 1704: 127\u2013136.","DOI":"10.1016\/j.brainres.2018.10.006"},{"key":"ref139","doi-asserted-by":"publisher","unstructured":"Ji N, Lu S, Xu B, Guan X, Xian Z, Geng D, et al. Levodopa-synergistic CBT intervention improves Parkinson\u2019s disease with anxiety disorder by regulating the BDNF\/PI3K\/AKT pathway. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2025; 46: 2137\u20132148.","DOI":"10.1007\/s10072-025-07988-0"},{"key":"ref140","doi-asserted-by":"publisher","unstructured":"Lian T, Zhang W, Li D, Guo P, He M, Zhang Y, et al. Parkinson\u2019s disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins. BMC Geriatrics. 2024; 24: 433.","DOI":"10.1186\/s12877-024-04854-0"},{"key":"ref141","doi-asserted-by":"publisher","unstructured":"Zhou W, Zeng T, Liu D, Pang R, Gong L. Association between inflammatory markers (SII and SIRI) and anxiety levels in Parkinson\u2019s disease. Frontiers in Psychiatry. 2025; 16: 1635817.","DOI":"10.3389\/fpsyt.2025.1635817"},{"key":"ref142","doi-asserted-by":"publisher","unstructured":"Zhao J, Jia H, Ma P, Zhu D, Fang Y. Multidimensional mechanisms of anxiety and depression in Parkinson\u2019s disease: Integrating neuroimaging, neurocircuits, and molecular pathways. Pharmacological Research. 2025; 215: 107717.","DOI":"10.1016\/j.phrs.2025.107717"},{"key":"ref143","doi-asserted-by":"publisher","unstructured":"Blundell EK, Grover LE, Stott J, Schrag A. The experience of Anxiety for people with Parkinson\u2019s disease. NPJ Parkinson\u2019s Disease. 2023; 9: 75.","DOI":"10.1038\/s41531-023-00512-1"},{"key":"ref144","doi-asserted-by":"publisher","unstructured":"Chen JJ, Marsh L. Anxiety in Parkinson\u2019s disease: identification and management. Therapeutic Advances in Neurological Disorders. 2014; 7: 52\u201359.","DOI":"10.1177\/1756285613495723"},{"key":"ref145","doi-asserted-by":"publisher","unstructured":"Aarsland D, Marsh L, Schrag A. Neuropsychiatric symptoms in Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2009; 24: 2175\u20132186.","DOI":"10.1002\/mds.22589"},{"key":"ref146","doi-asserted-by":"publisher","unstructured":"Kehagia AA. Neuropsychiatric Symptoms in Parkinson\u2019s Disease: Beyond Complications. Frontiers in Psychiatry. 2016; 7: 110.","DOI":"10.3389\/fpsyt.2016.00110"},{"key":"ref147","unstructured":"Bla\u017eekovi\u0107 A, Borove\u010dki F. Psychiatric Comorbidities in Parkinson\u2019s Disease Seen through the Prism of Genomics and Epigenetics. Psychiatria Danubina. 2021; 33: 456\u2013462."},{"key":"ref148","doi-asserted-by":"publisher","unstructured":"Trevisan L, Gaudio A, Monfrini E, Avanzino L, Di Fonzo A, Mandich P. Genetics in Parkinson\u2019s disease, state-of-the-art and future perspectives. British Medical Bulletin. 2024; 149: 60\u201371.","DOI":"10.1093\/bmb\/ldad035"},{"key":"ref149","doi-asserted-by":"publisher","unstructured":"Reyes-P\u00e9rez P, Garc\u00eda-Mar\u00edn LM, Aman AM, Antar T, Flores-Ocampo V, Mitchell BL, et al. Investigating the Shared Genetic Etiology Between Parkinson\u2019s Disease and Depression. Journal of Parkinson\u2019s Disease. 2024; 14: 483\u2013493.","DOI":"10.3233\/JPD-230176"},{"key":"ref150","doi-asserted-by":"publisher","unstructured":"Lunati A, Lesage S, Brice A. The genetic landscape of Parkinson\u2019s disease. Revue Neurologique. 2018; 174: 628\u2013643.","DOI":"10.1016\/j.neurol.2018.08.004"},{"key":"ref151","doi-asserted-by":"publisher","unstructured":"Magistrelli L, Contaldi E, Comi C. The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson\u2019s Disease. Life (Basel, Switzerland). 2021; 11: 804.","DOI":"10.3390\/life11080804"},{"key":"ref152","doi-asserted-by":"publisher","unstructured":"Kao AW, Racine CA, Quitania LC, Kramer JH, Christine CW, Miller BL. Cognitive and neuropsychiatric profile of the synucleinopathies: Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Alzheimer Disease and Associated Disorders. 2009; 23: 365\u2013370.","DOI":"10.1097\/WAD.0b013e3181b5065d"},{"key":"ref153","doi-asserted-by":"publisher","unstructured":"Teravskis PJ, Covelo A, Miller EC, Singh B, Martell-Mart\u00ednez HA, Benneyworth MA, et al. A53T Mutant Alpha-Synuclein Induces Tau-Dependent Postsynaptic Impairment Independently of Neurodegenerative Changes. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience. 2018; 38: 9754\u20139767.","DOI":"10.1523\/JNEUROSCI.0344-18.2018"},{"key":"ref154","doi-asserted-by":"publisher","unstructured":"Konno T, Ross OA, Puschmann A, Dickson DW, Wszolek ZK. Autosomal dominant Parkinson\u2019s disease caused by SNCA duplications. Parkinsonism & Related Disorders. 2016; 22 Suppl 1: S1\u2013S6.","DOI":"10.1016\/j.parkreldis.2015.09.007"},{"key":"ref155","doi-asserted-by":"publisher","unstructured":"Zarranz JJ, Alegre J, G\u00f3mez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology. 2004; 55: 164\u2013173.","DOI":"10.1002\/ana.10795"},{"key":"ref156","doi-asserted-by":"publisher","unstructured":"Olgiati S, Thomas A, Quadri M, Breedveld GJ, Graafland J, Eussen H, et al. Early-onset parkinsonism caused by alpha-synuclein gene triplication: Clinical and genetic findings in a novel family. Parkinsonism & Related Disorders. 2015; 21: 981\u2013986.","DOI":"10.1016\/j.parkreldis.2015.06.005"},{"key":"ref157","doi-asserted-by":"publisher","unstructured":"Safadi SS, Barber KR, Shaw GS. Impact of autosomal recessive juvenile Parkinson\u2019s disease mutations on the structure and interactions of the parkin ubiquitin-like domain. Biochemistry. 2011; 50: 2603\u20132610.","DOI":"10.1021\/bi200065g"},{"key":"ref158","doi-asserted-by":"publisher","unstructured":"Benbunan BR, Korczyn AD, Giladi N. Parkin mutation associated parkinsonism and cognitive decline, comparison to early onset Parkinson\u2019s disease. Journal of Neural Transmission (Vienna, Austria: 1996). 2004; 111: 47\u201357.","DOI":"10.1007\/s00702-003-0079-6"},{"key":"ref159","doi-asserted-by":"publisher","unstructured":"Barodia SK, Creed RB, Goldberg MS. Parkin and PINK1 functions in oxidative stress and neurodegeneration. Brain Research Bulletin. 2017; 133: 51\u201359.","DOI":"10.1016\/j.brainresbull.2016.12.004"},{"key":"ref160","doi-asserted-by":"publisher","unstructured":"Wei C, Sun Y, Chen N, Chen S, Xiu M, Zhang X. Interaction of oxidative stress and BDNF on executive dysfunction in patients with chronic schizophrenia. Psychoneuroendocrinology. 2020; 111: 104473.","DOI":"10.1016\/j.psyneuen.2019.104473"},{"key":"ref161","doi-asserted-by":"publisher","unstructured":"Smeland OB, Shadrin A, Bahrami S, Broce I, Tesli M, Frei O, et al. Genome-wide Association Analysis of Parkinson\u2019s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci. Biological Psychiatry. 2021; 89: 227\u2013235.","DOI":"10.1016\/j.biopsych.2020.01.026"},{"key":"ref162","doi-asserted-by":"publisher","unstructured":"Zhao X, Sun L, Sun YH, Ren C, Chen J, Wu ZQ, et al. Association of HTR2A T102C and A-1438G polymorphisms with susceptibility to major depressive disorder: a meta-analysis. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2014; 35: 1857\u20131866.","DOI":"10.1007\/s10072-014-1970-7"},{"key":"ref163","doi-asserted-by":"publisher","unstructured":"Kargbo RB. Neuropharmacological Advances: Harnessing 5-HT2A Receptor Modulators and Psychoplastogens. ACS Medicinal Chemistry Letters. 2024; 15: 171\u2013173.","DOI":"10.1021\/acsmedchemlett.4c00003"},{"key":"ref164","doi-asserted-by":"publisher","unstructured":"Louca Jounger S, Christidis N, Hedenberg-Magnusson B, List T, Svensson P, Schalling M, et al. Polymorphisms in the HTR2A and HTR3A Genes Contribute to Pain in TMD Myalgia. Frontiers in Oral Health. 2021; 2: 647924.","DOI":"10.3389\/froh.2021.647924"},{"key":"ref165","doi-asserted-by":"publisher","unstructured":"Smith RM, Papp AC, Webb A, Ruble CL, Munsie LM, Nisenbaum LK, et al. Multiple regulatory variants modulate expression of 5-hydroxytryptamine 2A receptors in human cortex. Biological Psychiatry. 2013; 73: 546\u2013554.","DOI":"10.1016\/j.biopsych.2012.09.028"},{"key":"ref166","unstructured":"Sujitha SP, Nair A, Banerjee M, Lakshmanan S, Harshavaradhan S, Gunasekaran S, et al. 5-Hydroxytryptamine (serotonin) 2A receptor gene polymorphism is associated with schizophrenia. The Indian Journal of Medical Research. 2014; 140: 736\u2013743."},{"key":"ref167","doi-asserted-by":"publisher","unstructured":"Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Archives of Medical Science: AMS. 2015; 11: 1164\u20131178.","DOI":"10.5114\/aoms.2015.56342"},{"key":"ref168","doi-asserted-by":"publisher","unstructured":"Tsai SJ. Salivary gland low-intensity pulsed ultrasound (LIPUS) stimulation as a potential treatment for various BDNF-implicated neuropsychiatric disorders. Medical Hypotheses. 2020; 137: 109560.","DOI":"10.1016\/j.mehy.2020.109560"},{"key":"ref169","doi-asserted-by":"publisher","unstructured":"Lin CC, Huang TL. Brain-derived neurotrophic factor and mental disorders. Biomedical Journal. 2020; 43: 134\u2013142.","DOI":"10.1016\/j.bj.2020.01.001"},{"key":"ref170","doi-asserted-by":"publisher","unstructured":"Sheikh HI, Hayden EP, Kryski KR, Smith HJ, Singh SM. Genotyping the BDNF rs6265 (val66met) polymorphism by one-step amplified refractory mutation system PCR. Psychiatric Genetics. 2010; 20: 109\u2013112.","DOI":"10.1097\/YPG.0b013e32833a2038"},{"key":"ref171","doi-asserted-by":"publisher","unstructured":"Ramezani M, Ruskey JA, Martens K, Kibreab M, Javer Z, Kathol I, et al. Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson\u2019s Disease. Frontiers in Neurology. 2021; 11: 587992.","DOI":"10.3389\/fneur.2020.587992"},{"key":"ref172","doi-asserted-by":"publisher","unstructured":"Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science (New York, N.Y.). 2006; 314: 140\u2013143.","DOI":"10.1126\/science.1129663"},{"key":"ref173","doi-asserted-by":"publisher","unstructured":"Marcus C, Mena E, Subramaniam RM. Brain PET in the diagnosis of Alzheimer\u2019s disease. Clinical Nuclear Medicine. 2014; 39: e413\u2013e413\u2013e422; quiz e423\u2013e426.","DOI":"10.1097\/RLU.0000000000000547"},{"key":"ref174","doi-asserted-by":"publisher","unstructured":"Baba T, Hosokai Y, Nishio Y, Kikuchi A, Hirayama K, Suzuki K, et al. Longitudinal study of cognitive and cerebral metabolic changes in Parkinson\u2019s disease. Journal of the Neurological Sciences. 2017; 372: 288\u2013293.","DOI":"10.1016\/j.jns.2016.11.068"},{"key":"ref175","doi-asserted-by":"publisher","unstructured":"Borroni B, Premi E, Formenti A, Turrone R, Alberici A, Cottini E, et al. Structural and functional imaging study in dementia with Lewy bodies and Parkinson\u2019s disease dementia. Parkinsonism & Related Disorders. 2015; 21: 1049\u20131055.","DOI":"10.1016\/j.parkreldis.2015.06.013"},{"key":"ref176","doi-asserted-by":"publisher","unstructured":"Owens-Walton C, Jakabek D, Power BD, Walterfang M, Hall S, van Westen D, et al. Structural and functional neuroimaging changes associated with cognitive impairment and dementia in Parkinson\u2019s disease. Psychiatry Research. Neuroimaging. 2021; 312: 111273.","DOI":"10.1016\/j.pscychresns.2021.111273"},{"key":"ref177","doi-asserted-by":"publisher","unstructured":"Ahmed ME, Selvakumar GP, Thangavel R, Kempuraj D, Raikwar SP, Zaheer S, et al. Immune Suppression of Glia Maturation Factor Reverses Behavioral Impairment, Attenuates Amyloid Plaque Pathology and Neuroinflammation in an Alzheimer\u2019s Disease Mouse Model. Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology. 2021; 16: 363\u2013375.","DOI":"10.1007\/s11481-020-09929-4"},{"key":"ref178","doi-asserted-by":"publisher","unstructured":"Domell\u00f6f ME, Lundin KF, Edstr\u00f6m M, Forsgren L. Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson\u2019s disease. Parkinsonism & Related Disorders Parkinsonism. 2017; 38: 41\u201347.","DOI":"10.1016\/j.parkreldis.2017.02.017"},{"key":"ref179","doi-asserted-by":"publisher","unstructured":"Baba T, Takeda A, Murakami A, Koga T, Isomura T, Mori E, et al. Effect of donepezil for dementia prevention in Parkinson\u2019s disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial. EClinicalMedicine. 2022; 51: 101571.","DOI":"10.1016\/j.eclinm.2022.101571"},{"key":"ref180","doi-asserted-by":"publisher","unstructured":"An HM, Lin C, Gu C, Chen JJ, Sun WX, Jin M, et al. Di-Huang-Yi-Zhi herbal formula attenuates amyloid-\u03b2-induced neurotoxicity in PC12 cells. Experimental and Therapeutic Medicine. 2017; 13: 3003\u20133008.","DOI":"10.3892\/etm.2017.4368"},{"key":"ref181","doi-asserted-by":"publisher","unstructured":"Gu C, Shen T, An H, Yuan C, Zhou J, Ye Q, et al. Combined therapy of Di-Huang-Yi-Zhi with Donepezil in patients with Parkinson\u2019s disease dementia. Neuroscience Letters. 2015; 606: 13\u201317.","DOI":"10.1016\/j.neulet.2015.08.019"},{"key":"ref182","doi-asserted-by":"publisher","unstructured":"Zhang C, Zang Y, Song Q, Li H, Hu L, Zhao W, et al. The efficacy of a \u201ccocktail therapy\u201d on Parkinson\u2019s disease with dementia. Neuropsychiatric Disease and Treatment. 2019; 15: 1639\u20131647.","DOI":"10.2147\/NDT.S179453"},{"key":"ref183","doi-asserted-by":"publisher","unstructured":"Pathak S, Nadar R, Kim S, Liu K, Govindarajulu M, Cook P, et al. The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies. International Journal of Molecular Sciences. 2024; 25: 853.","DOI":"10.3390\/ijms25020853"},{"key":"ref184","doi-asserted-by":"publisher","unstructured":"Hestad K, Alexander J, Rootwelt H, Aaseth JO. The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases. Biomolecules. 2022; 12: 998.","DOI":"10.3390\/biom12070998"},{"key":"ref185","doi-asserted-by":"publisher","unstructured":"Frost ED, Shi SX, Byroju VV, Pitton Rissardo J, Donlon J, Vigilante N, et al. Galantamine-Memantine Combination in the Treatment of Parkinson\u2019s Disease Dementia. Brain Sciences. 2024; 14: 1163.","DOI":"10.3390\/brainsci14121163"},{"key":"ref186","doi-asserted-by":"publisher","unstructured":"Samanta S, Bisht M, Kanimozhi M, Kumar N, Handu SS. Association of depression with disease duration, quality of life and adherence in Parkinson\u2019s disease: A cross sectional study. Journal of Family Medicine and Primary Care. 2023; 12: 1406\u20131411.","DOI":"10.4103\/jfmpc.jfmpc_2288_22"},{"key":"ref187","doi-asserted-by":"publisher","unstructured":"Ramanzini LG, Camargo LFM, Silveira JOF, Bochi GV. Inflammatory markers and depression in Parkinson\u2019s disease: a systematic review. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2022; 43: 6707\u20136717.","DOI":"10.1007\/s10072-022-06363-7"},{"key":"ref188","doi-asserted-by":"publisher","unstructured":"Wang H, Zhao Y, Schrag A. Development of anxiety in early Parkinson\u2019s disease: A clinical and biomarker study. European Journal of Neurology. 2023; 30: 2661\u20132668.","DOI":"10.1111\/ene.15890"},{"key":"ref189","doi-asserted-by":"publisher","unstructured":"Liu H, Zhao H, Huang D. Circulating miR-425 can be a biomarker for depression in patients with Parkinson\u2019s disease. Clinical Neurology and Neurosurgery. 2025; 255: 108969.","DOI":"10.1016\/j.clineuro.2025.108969"},{"key":"ref190","doi-asserted-by":"publisher","unstructured":"Mollenhauer B, Weintraub D. The depressed brain in Parkinson\u2019s disease: Implications for an inflammatory biomarker. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114: 3004\u20133005.","DOI":"10.1073\/pnas.1700737114"},{"key":"ref191","doi-asserted-by":"publisher","unstructured":"Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S. Depression in Parkinson\u2019s Disease: A Narrative Review. Cureus. 2022; 14: e27750.","DOI":"10.7759\/cureus.27750"},{"key":"ref192","doi-asserted-by":"publisher","unstructured":"Elcadi K, Klevor R, Louhab N, Kissani N, Chraa M. Exploring the Efficacy of Cognitive Behavioral Therapy for Managing Anxiety in People with Parkinson\u2019s Disease. NeuroSci. 2025; 6: 93.","DOI":"10.3390\/neurosci6040093"},{"key":"ref193","doi-asserted-by":"publisher","unstructured":"Yu X, Wu Q, Liu Y, Han P, Chen X, Guo Q. Cognitive behavioral therapy for anxiety and depression symptoms in people of Parkinson\u2019s disease: a systematic review and meta-analysis. Frontiers in Aging Neuroscience. 2025; 17: 1440850.","DOI":"10.3389\/fnagi.2025.1440850"},{"key":"ref194","doi-asserted-by":"publisher","unstructured":"van Wegen EEH, van Balkom TD, Hirsch MA, Rutten S, van den Heuvel OA. Non-Pharmacological Interventions for Depression and Anxiety in Parkinson\u2019s Disease. Journal of Parkinson\u2019s Disease. 2024; 14: S135\u2013S146.","DOI":"10.3233\/JPD-230228"},{"key":"ref195","doi-asserted-by":"publisher","unstructured":"Yue C, Wang N, Zhai H, Yuan Z, Cui Y, Quan J, et al. Adenosine signalling drives antidepressant actions of ketamine and ECT. Nature. 2026; 649: 423\u2013431.","DOI":"10.1038\/s41586-025-09755-9"},{"key":"ref196","doi-asserted-by":"publisher","unstructured":"Han WM, Hao XB, Hong YX, Zhao SS, Chen XC, Wang R, et al. NMDARs antagonist MK801 suppresses LPS-induced apoptosis and mitochondrial dysfunction by regulating subunits of NMDARs via the CaM\/CaMKII\/ERK pathway. Cell Death Discovery. 2023; 9: 59.","DOI":"10.1038\/s41420-023-01362-9"},{"key":"ref197","doi-asserted-by":"publisher","unstructured":"Anderson G. Enteric glial cell and astrocyte melatonin regulation in Parkinson disease pathogenesis and pathophysiology. Academia Biology. 2026; 4. https:\/\/doi:","DOI":"10.20935\/AcadBiol8130"},{"key":"ref198","doi-asserted-by":"publisher","unstructured":"Pang CS, Mulnier C, Pang SF, Yang JC. Effects of halothane, pentobarbital and ketamine on serum melatonin levels in the early scotophase in New Zealand white rabbits. Biological Signals and Receptors. 2001; 10: 310\u2013316.","DOI":"10.1159\/000046898"},{"key":"ref199","doi-asserted-by":"publisher","unstructured":"Li J, MD, Wang L, MD, Zhang Y, MD, Meng R, MD, Zhu B, MD, Chen JDZ, PHD, et al. Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia with sleep disturbance via enhanced vagal activity: a randomized controlled trial. International Journal of Surgery (London, England). 2026; 112: 961\u2013972.","DOI":"10.1097\/JS9.0000000000003296"},{"key":"ref200","doi-asserted-by":"publisher","unstructured":"Zhang Y, Zou N, Xin C, Wang Y, Zhang Z, Rong P, et al. Transcutaneous auricular vagal nerve stimulation modulates blood glucose in ZDF rats via intestinal melatonin receptors and melatonin secretion. Frontiers in Neuroscience. 2024; 18: 1471387.","DOI":"10.3389\/fnins.2024.1471387"},{"key":"ref201","doi-asserted-by":"publisher","unstructured":"Carey G, G\u00f6rmezo\u011flu M, de Jong JJA, Hofman PAM, Backes WH, Dujardin K, et al. Neuroimaging of Anxiety in Parkinson\u2019s Disease: A Systematic Review. Movement Disorders: Official Journal of the Movement Disorder Society. 2021; 36: 327\u2013339.","DOI":"10.1002\/mds.28404"},{"key":"ref202","doi-asserted-by":"publisher","unstructured":"Wang X, Sun G, Tang M, Li D, Qi J, Wang C, et al. Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation. Cell Proliferation. 2025; 58: e70005.","DOI":"10.1111\/cpr.70005"},{"key":"ref203","doi-asserted-by":"publisher","unstructured":"Kim H, Kang S, Cho B, An S, Kim Y, Kim J. Parkinson\u2019s Disease Modeling Using Directly Converted 3D Induced Dopaminergic Neuron Organoids and Assembloids. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2025; 12: e2412548.","DOI":"10.1002\/advs.202412548"},{"key":"ref204","doi-asserted-by":"publisher","unstructured":"Tran HD, Denman CR, Shin MK, Jeon D, Kuhn B, Jo J. Establishment of TH-EGFP human embryonic stem cell line for specific labeling of dopaminergic neurons. Stem Cell Research. 2024; 81: 103613.","DOI":"10.1016\/j.scr.2024.103613"},{"key":"ref205","doi-asserted-by":"publisher","unstructured":"Zhou ZD, Saw WT, Ho PGH, Zhang ZW, Zeng L, Chang YY, et al. The role of tyrosine hydroxylase-dopamine pathway in Parkinson\u2019s disease pathogenesis. Cellular and Molecular Life Sciences: CMLS. 2022; 79: 599.","DOI":"10.1007\/s00018-022-04574-x"},{"key":"ref206","doi-asserted-by":"publisher","unstructured":"Kim SJ, Jung WH, Choe MS, Jeon YS, Lee MY. Modeling Synucleinopathy Using hESC-Derived Cerebral Organoids. Cells. 2025; 14: 1436.","DOI":"10.3390\/cells14181436"},{"key":"ref207","doi-asserted-by":"publisher","unstructured":"Tran HD, Shin MK, Yeo XY, Jung S, Junaid M, Lim SB, et al. A human striatal-midbrain assembloid model of alpha-synuclein propagation. Brain: a Journal of Neurology. 2026; 149: 867\u2013883.","DOI":"10.1093\/brain\/awaf326"},{"key":"ref208","doi-asserted-by":"publisher","unstructured":"Gomez-Giro G, Frangenberg D, Vega D, Zagare A, Barmpa K, Antony PMA, et al. \u03b1-Synuclein Pathology Spreads in a Midbrain-Hindbrain Assembloid Model. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2025; 12: e2409040.","DOI":"10.1002\/advs.202409040"},{"key":"ref209","doi-asserted-by":"publisher","unstructured":"Mohamed NV, Sirois J, Ramamurthy J, Mathur M, L\u00e9pine P, Deneault E, et al. Midbrain organoids with an SNCA gene triplication model key features of synucleinopathy. Brain Communications. 2021; 3: fcab223.","DOI":"10.1093\/braincomms\/fcab223"},{"key":"ref210","doi-asserted-by":"publisher","unstructured":"Jin Y, Li F, Li Z, Ikezu TC, O\u2019Leary J, Selvaraj M, et al. Modeling Lewy body disease with SNCA triplication iPSC-derived cortical organoids and identifying therapeutic drugs. Science Advances. 2024; 10: eadk3700.","DOI":"10.1126\/sciadv.adk3700"},{"key":"ref211","doi-asserted-by":"publisher","unstructured":"Muwanigwa MN, Modamio-Chamarro J, Antony PMA, Gomez-Giro G, Kr\u00fcger R, Bolognin S, et al. Alpha-synuclein pathology is associated with astrocyte senescence in a midbrain organoid model of familial Parkinson\u2019s disease. Molecular and Cellular Neurosciences. 2024; 128: 103919.","DOI":"10.1016\/j.mcn.2024.103919"},{"key":"ref212","doi-asserted-by":"publisher","unstructured":"Becerra-Calixto A, Mukherjee A, Ramirez S, Sepulveda S, Sinha T, Al-Lahham R, et al. Lewy Body-like Pathology and Loss of Dopaminergic Neurons in Midbrain Organoids Derived from Familial Parkinson\u2019s Disease Patient. Cells. 2023; 12: 625.","DOI":"10.3390\/cells12040625"},{"key":"ref213","doi-asserted-by":"publisher","unstructured":"Kano M, Takanashi M, Oyama G, Yoritaka A, Hatano T, Shiba-Fukushima K, et al. Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinson\u2019s Disease. 2020; 6: 33.","DOI":"10.1038\/s41531-020-00137-8"},{"key":"ref214","doi-asserted-by":"publisher","unstructured":"Gerasimova E, Beenen AC, Kachkin D, Regensburger M, Zundler S, Blumenthal DB, et al. Novel co-culture model of T cells and midbrain organoids for investigating neurodegeneration in Parkinson\u2019s disease. NPJ Parkinson\u2019s Disease. 2025; 11: 36.","DOI":"10.1038\/s41531-025-00882-8"},{"key":"ref215","doi-asserted-by":"publisher","unstructured":"Zhong C, Gao X, Chen Q, Guan B, Wu W, Ma Z, et al. R406 and its structural analogs reduce SNCA\/\u03b1-synuclein levels via autophagic degradation. Autophagy. 2025; 21: 1945\u20131961.","DOI":"10.1080\/15548627.2025.2483886"},{"key":"ref216","doi-asserted-by":"publisher","unstructured":"Zhang Q, Liu M, Xu Y, Lee J, Jones B, Li B, et al. Tilorone mitigates the propagation of \u03b1-synucleinopathy in a midbrain-like organoid model. Journal of Translational Medicine. 2024; 22: 816.","DOI":"10.1186\/s12967-024-05551-7"},{"key":"ref217","doi-asserted-by":"publisher","unstructured":"Sai M, Hank EC, Tai HM, Kasch T, Lewandowski M, Vincendeau M, et al. Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing. Communications Chemistry. 2024; 7: 149.","DOI":"10.1038\/s42004-024-01224-0"},{"key":"ref218","doi-asserted-by":"publisher","unstructured":"Yangzom T, Chen A, Liang KX. Generation of 3D Midbrain Organoids from Human-Induced Pluripotent Stem Cells. Journal of Visualized Experiments: JoVE. 2025;  https:\/\/doi.org\/","DOI":"10.3791\/67228"},{"key":"ref219","doi-asserted-by":"publisher","unstructured":"Smits LM, Reinhardt L, Reinhardt P, Glatza M, Monzel AS, Stanslowsky N, et al. Modeling Parkinson\u2019s disease in midbrain-like organoids. NPJ Parkinson\u2019s Disease. 2019; 5: 5.","DOI":"10.1038\/s41531-019-0078-4"},{"key":"ref220","doi-asserted-by":"publisher","unstructured":"Zagare A, Sauter T, Barmpa K, Pacheco M, Kr\u00fcger R, Schwamborn JC, et al. MIRO1 mutation leads to metabolic maladaptation resulting in Parkinson\u2019s disease-associated dopaminergic neuron loss. NPJ Systems Biology and Applications. 2025; 11: 37.","DOI":"10.1038\/s41540-025-00509-x"},{"key":"ref221","doi-asserted-by":"publisher","unstructured":"Zagare A, Hemedan A, Almeida C, Frangenberg D, Gomez-Giro G, Antony P, et al. Insulin Resistance Is a Modifying Factor for Parkinson\u2019s Disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2025; 40: 67\u201376.","DOI":"10.1002\/mds.30039"},{"key":"ref222","doi-asserted-by":"publisher","unstructured":"Geng L, Gao W, Saiyin H, Li Y, Zeng Y, Zhang Z, et al. MLKL deficiency alleviates neuroinflammation and motor deficits in the \u03b1-synuclein transgenic mouse model of Parkinson\u2019s disease. Molecular Neurodegeneration. 2023; 18: 94.","DOI":"10.1186\/s13024-023-00686-5"},{"key":"ref223","doi-asserted-by":"publisher","unstructured":"Zagare A, Kurlovics J, Almeida C, Ferrante D, Frangenberg D, Vitali A, et al. Insulin resistance compromises midbrain organoid neuronal activity and metabolic efficiency predisposing to Parkinson\u2019s disease pathology. Journal of Tissue Engineering. 2025; 16: 20417314241295928.","DOI":"10.1177\/20417314241295928"},{"key":"ref224","doi-asserted-by":"publisher","unstructured":"Rosety I, Zagare A, Saraiva C, Nickels S, Antony P, Almeida C, et al. Impaired neuron differentiation in GBA-associated Parkinson\u2019s disease is linked to cell cycle defects in organoids. NPJ Parkinson\u2019s Disease. 2023; 9: 166.","DOI":"10.1038\/s41531-023-00616-8"},{"key":"ref225","doi-asserted-by":"publisher","unstructured":"Morrone Parfitt G, Coccia E, Goldman C, Whitney K, Reyes R, Sarrafha L, et al. Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson\u2019s disease model. Nature Communications. 2024; 15: 447.","DOI":"10.1038\/s41467-024-44732-2"},{"key":"ref226","doi-asserted-by":"publisher","unstructured":"Wulansari N, Darsono WHW, Woo HJ, Chang MY, Kim J, Bae EJ, et al. Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson\u2019s disease-linked DNAJC6 mutations. Science Advances. 2021; 7: eabb1540.","DOI":"10.1126\/sciadv.abb1540"},{"key":"ref227","doi-asserted-by":"publisher","unstructured":"Tatullo M, Cocco T, Ferretta A, Caroppo R, Marrelli B, Spagnuolo G, et al. Unveiling the Neurodegenerative Alterations through Oral Stem Cells. Journal of Dental Research. 2024; 103: 1100\u20131108.","DOI":"10.1177\/00220345241265661"},{"key":"ref228","doi-asserted-by":"publisher","unstructured":"Zheng X, Chen J, Huang Z, Zhang Y, Zhou L. Efficacy and safety assessment of homotopical transplantation of iPSCs-derived midbrain organoids into the substantia nigra of Parkinsonian rats. Bioengineering & Translational Medicine. 2025; 10: e70014.","DOI":"10.1002\/btm2.70014"},{"key":"ref229","doi-asserted-by":"publisher","unstructured":"Fu CL, Dong BC, Jiang X, Li D, Yao J. A cell therapy approach based on iPSC-derived midbrain organoids for the restoration of motor function in a Parkinson\u2019s disease mouse model. Heliyon. 2024; 10: e24234.","DOI":"10.1016\/j.heliyon.2024.e24234"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/5\/10.31083\/JIN50055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:27:00Z","timestamp":1780129620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/5\/10.31083\/JIN50055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":229,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0219-6352(26)01138-1"],"URL":"https:\/\/doi.org\/10.31083\/jin50055","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"article-number":"50055"}}