Correlation of Serum Malondialdehyde with Motor Severity and Cognitive Function in Parkinson’s Disease
Research
DOI:
https://doi.org/10.55175/cdk.v53i09.2326Kata Kunci:
Cognitive function, malondialdehyde, motor symptom, Parkinson’s diseaseAbstrak
Introduction: Accumulating research supports the view that oxidative stress is a key driver of the pathological processes underlying Parkinson’s disease (PD). Among biomarkers of oxidative injury, malondialdehyde (MDA)—a key lipid peroxidation product—is frequently utilized to quantify oxidative stress; however, its relationship with motor symptom severity and cognitive function in PD remains insufficiently explored. This study aimed to examine the association between serum MDA levels, motor symptom severity, and cognitive function in patients with Parkinson’s disease. Methods: This cross-sectional study included 35 patients diagnosed with PD. Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) and stratified into mild, moderate, and severe levels. Cognitive assessment utilized the Montreal Cognitive Assessment–Indonesia (MoCA-Ina) alongside trail making test part A (TMT-A) and trail making test part B (TMT-B). Serum MDA concentrations were measured using the thiobarbituric acid reactive substances (TBARS) assay. Statistical assessment was conducted using Spearman’s rank correlation alongside the Mann–Whitney U test. Results: This study revealed a meaningful positive linkage between MDA concentrations and motor symptom severity (r = 0.421, p = 0.012). Posthoc analysis indicated that patients with moderate and severe motor symptoms had higher MDA levels than those with mild symptoms (p = 0.032; p = 0.022), while no discrepancy was found between the moderate and severe groups (p = 0.421). MDA levels showed no significant association with MoCA-Ina or TMT-A performance (r = 0.206, p = 0.235; r = 0.079, p = 0.684), but patients with abnormal TMT-B performance had higher MDA levels than participants with normal results (p = 0.043). Conclusion: MDA level is linked to greater motor symptom severity and executive dysfunction in PD. The results imply that MDA may act as a promising biomarker reflecting oxidative damage–driven neurodegeneration underlying motor and executive impairments in PD.
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Referensi
Jankovic J, Tan EK. Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2020;91(8):795–808. doi:10.1136/jnnp-2019-322338.
Duarte-Jurado AP, Gopar-Cuevas Y, Saucedo-Cardenas O, Loera-Arias MDJ, Montes-de-Oca-Luna R, Garcia-Garcia A, et al. Antioxidant therapeutics in Parkinson’s disease: current challenges and opportunities. Antioxidants. 2021;10(3):453. doi: 10.3390/antiox10030453.
Wei Z, Li X, Li X, Liu Q, Cheng Y. Oxidative stres in Parkinson’s disease: systematic review and meta-nalysis. Front Mol Neurosci. 2018;11:236. doi:10.3389/fnmol.2018.00236.
Yang K, Wu Z, Long J, Li W, Wang X, Hu N, et al. White matter changes in Parkinson’s disease. NPJ Parkinsons Dis. 2023;9(1):150. doi:10.1038/s41531-023-00592-z.
Isobe C, Abe T, Terayama Y. Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson’s disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process. Neuroscience Letters. 2010;469(1):159–63. doi: 10.1016/j.neulet.2009.11.065.
Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stres in Parkinson’s disease. Eur Neurol. 2007;58(2):78–83. doi: 10.1159/000103641.
De Farias CC, Maes M, Bonifcio KL, Bortolasci CC, De Souza Nogueira A, Brinholi FF, et al. Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson’s disease and its progression: disease and staging biomarkers and new drug targets. Neuroscience Letters. 2016;617:66–71. doi: 10.1016/j.neulet.2016.02.011.
Gokce Cokal B, Yurtdas M, Keskin Guler S, Gunes HN, Atac Ucar C, Aytac B, et al. Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehid levels in patients with Parkinson’s disease. Neurol Sci. 2017;38(3):425–31. doi:10.1007/s10072-016-2782-8.
Sanyal J, Bandyopadhyay SK, Banerjee TK, . Plasma levels of lipid peroxides in patients with Parkinson's disease. Eur Rev Med Pharmacol Sci. 2009;13(2):129–32. PMID: 19499848.
Tsikas D. Assessment of lipid peroxidation by measuring malondialdehid (MDA) and relatives in biological samples: analytical and biological challenges. Analytical Biochem. 2017;524:13–30. doi: 10.1016/j.ab.2016.10.021.
Khan Z, Ali SA. Oxidative stres-related biomarkers in Parkinson's disease: a systematic review and meta-analysis. Iran J Neurol. 2018;17(3):137–144. PMID: 30886681.
Vida C, Kobayashi H, Garrido A, Martínez De Toda I, Carro E, Molina JA, et al. Lymphoproliferation impairment and oxidative stres in blood cells from early Parkinson’s disease patients. Int J Mol Sci. 2019;20(3):771. doi: 10.3390/ijms20030771.
Mileti J, Drakuli D, Peji S, Petkovi M, Ili TV, Miljkovi M, et al. Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson’s disease. Internat J Neurosci. 2018;128(7):600–7. doi: 10.1080/00207454.2017.1403916.
Cristalli DO, Arnal N, Marra FA, de Alaniz MJT, Marra CA. Peripheral markers in neurodegenerative patients and their first-degree relatives. J Neurol Sci. 2012;314(1–2):48–56. doi: 10.1016/j.jns.2011.11.001.
Ayala A, Muoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyd and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity. 2014;2014:360438 . doi: 10.1155/2014/360438.
Mythri RB, Venkateshappa C, Harish G, Mahadevan A, Muthane UB, Yasha TC, et al. Evaluation of markers of oxidative stres, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson’s disease brains. Neurochem Res. 2011;36(8):1452–63. doi: 10.1007/s11064-011-0471-9.
Li X, Chen C, Pan T. Trends and hotspots in non-motor symptoms of Parkinson's disease: a 10-year bibliometric analysis. Front Aging Neurosci. 2024;16:1335550. doi: 10.3389/fnagi.2024.1335550.
Simon-Gozalbo A, Rodriguez-Blazquez C, Forjaz MJ, Martinez-Martin P. Clinical characterization of Parkinson's disease patients with cognitive impairment. Front Neurol. 2020;11:731. doi: 10.3389/fneur.2020.00731.
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatr. 1992;55(3):181–4. doi: 10.1136/jnnp.55.3.181.
Martinez-Martin P, Rodriguez-Blzquez C, Mario Alvarez. Parkinson's disease severity levels and MDS-unified Parkinson's disease rating scale. Parkinsonism Relat Disord. 2015;21(1):50–4. doi: 10.1016/j.parkreldis.2014.10.026.
Nasreddine ZS, Phillips NA, Bdirian V. The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–9. doi: 10.1111/j.1532-5415.2005.53221.x.
Dalrymple-Alford JC, MacAskill MR, Nakas CT, Livingston L, Graham C, Crucian GP,et al . The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology. 2010;75(19):1717-25. doi:10.1212/WNL.0b013e3181fc29c9.
Tombaugh TN. Trail making test A and B: normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19(2):203–14. doi:10.1016/S0887-6177(03)00039-8.
Snchez-Cubillo I, Periez JA, Adrover-Roig D, Rodrguez-Snchez JM, Ros-Lago M, Tirapu J, et al. Construct validity of the trail making test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. J Int Neuropsychol Soc. 2009;15(3):438–50. doi: 10.1017/S1355617709090626.
Herbig E, Mcke D, Barbe MT, Thies T. Executive dysfunctions impair and levodopa improves articulatory timing in Parkinson's disease. Front Hum Neurosci. 2025;19:1580376. doi: 10.3389/fnhum.2025.1580376.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8. doi:10.1016/0003-2697(79)90738-3.
Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, et al. Basal lipideroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem. 1989;52(2):381–9. doi: 10.1111/j.1471-4159.1989.tb09133.x.
Thakkar H, Chatterjee S, Verma A, Chandrasekar N, Khairnar A, Shah RP. Malondialdehyde mediated alpha-synuclein aggregation: a plausible etiology of Parkinson's disease in oxidative stress. Chem Res Toxicol. 2025;38(4):573–82. doi: 10.1021/acs.chemrestox.4c00348.
Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson's disease. J Parkinsons Dis. 2013;3(4):461–91. doi: 10.3233/JPD-130230.
Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev. 2012;2012:428010. doi:10.1155/2012/428010.
Chen CM, Liu JL, Wu YR, Chen YC, Cheng HS, Cheng ML, et al. Increased oxidative damage in peripheral blood correlates with severity of Parkinson's disease. Neurobiol Dis. 2009;33(3):429–35. doi: 10.1016/j.nbd.2008.11.011.
Olufunmilayo EO, Gerke-Duncan MB, Holsinger RMD. Oxidative stress and antioxidants in neurodegenerative disorders. Antioxidants (Basel). 2023;12(2):517. doi: 10.3390/antiox12020517.
Bej E, Cesare P, Volpe AR, d'Angelo M, Castelli V. Oxidative stress and neurodegeneration: insights and therapeutic strategies for Parkinson's disease. Neurol Int. 2024;16(3):502–17. doi: 10.3390/neurolint16030037.
Aarsland D, Batzu L, Halliday GM,. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021;7(1):47. doi: 10.1038/s41572-021-00280-3.
Fang C, Lv L, Mao S, Dong H, Liu B. Cognition deficits in Parkinson's disease: mechanisms and treatment. Parkinsons Dis. 2020;2020:2076942. doi: 10.1155/2020/2076942.
Pagonabarraga J, Kulisevsky J. Cognitive impairment and dementia in Parkinson's disease. Neurobiol Dis. 2012;46(3):590–6. doi: 10.1016/j.nbd.2012.03.029.
Cao F, Guan X, Ma Y, Shao Y, Zhong J. Altered functional network associated with cognitive performance in early Parkinson disease measured by eigenvector centrality mapping. Front Aging Neurosci. 2020;12:554660. doi: 10.3389/fnagi.2020.554660.
Lewis SJG, Dove A, Robbins TW, Barker RA, Owen AM. Cognitive impairments in early Parkinson's disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci. 2003;23(15):6351–6. doi: 10.1523/JNEUROSCI.23-15-06351.2003.
Suresh E, Yadav S, Pallapotu R. Biochemical analysis of oxidative stress parameters in neurodegenerative disorders. Int J Curr Pharm Rev Res.2025;17(2):817–20.
Lezak MD, Howieson DB, Bigler ED, Tranel,D. Neuropsychological assessment. 5th ed. England: Oxford University Press; 2012.
Yang Q, Li C, Jiang F, Qiu J, Yang H, Tian Q,et al . Effects of oxidative stress and GDNF on patients with bipolar disorder: a prospective study. BMC Psychiatry. 2025;25(1):258. doi: 10.1186/s12888-025-06698-3.
Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005;65(8):1239–45. doi: 10.1212/01.wnl.0000180516.69442.95.
Rocha NP, Carreira EX, Prado ACA, Tavares F, Tavares M, Cardoso F, et al. Cognitive evaluation in Parkinson's disease: applying the movement disorder society recommendations in a population with a low level of formal education. Arq Neuropsiquiatr. 2023;81(2):119–27. doi:10.1055/s-0042-1759761.
Parker KL, Lamichhane D, Caetano MS, Narayanan NS. Executive dysfunction in Parkinson's disease and timing deficits. Front Integr Neurosci. 2013;7:75. doi: 10.3389/fnint.2013.00075.
Young CB, Cholerton B, Smith AM, . The Parkinson's disease composite of executive functioning: a measure for detecting cognitive decline in clinical trials. Neurology. 2024;103(2):e209609. doi: 10.1212/WNL.0000000000209609.
Pisani S, Gosse L, Wieretilo R, Ffytche D, Velayudhan L, Bhattacharyya S. Cognitive and executive impairments in Parkinson's disease psychosis: a Bayesian meta-analysis. J Neurol Neurosurg Psychiatry. 2024;95(3):277–87. doi: 10.1136/jnnp-2022-331028.
Rasool A, Manzoor R, Ullah K,. Oxidative stress and dopaminergic metabolism: a major PD pathogenic mechanism and basis of potential antioxidant therapies. CNS Neurol Disord Drug Targets. 2024;23(7):852–64. doi: 10.2174/1871527322666230609141519.
Liu J, Sun S, Chen Y. Superoxide dismutase modified the association of serum malondialdehid levels with cognitive decline among older adults: findings from the Chinese longitudinal healthy longevity survey. JAD. 2024;99(2):657–65. doi: 10.3233/JAD-231278
Fischer R, Maier O. Interrelation of oxidative stres and inflammation in neurodegenerative disease: role of TNF. Oxidative Med Cell Longevity. 2015;2015:610813. doi: 10.1155/2015/610813.
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