A bibliometric analysis of mechanisms and linkage studies on neurological disorders and statins over the past 20 years

Abstract

Background: Neurological disorders are one of the major contributors to the burden of disease, affecting the quality of life of the global population.Statins, known for their cholesterol-lowering properties, have garnered substantial interest due to their potential neuroprotective effects and association with subjective cognitive decline.The study aims to provide a comprehensive bibliometric analysis of the literature on the nexus between neurological disorders and statins.

Methods: Using VOSviewer (1.6.20), CiteSpace (6.3.1 and 5.7.R2), and R (4.4.1), the systematic bibliometric analysis offers valuable insights into the research landscape of neurological disorders and statins from 2004 to 2024.

Results: The findings reveal a notable increase in scholarly output on neurological disorders and statins over the past two decades, with a particular emphasis on clinical trials and pharmacological mechanisms of statins. The remarkable multidisciplinary nature of the field is an important reason for its continued development.Compared to initial exploratory research, recent studies have placed increased emphasis on the neuroprotective roles of statins and their therapeutic potential in managing neurological disorders.Future research is anticipated to focus on precision medicine and personalized therapeutic strategies involving statins.The United States, China and Germany are leading the way in this field of research.

Conclusion: The study's findings are instrumental in informing future research directions and contribute to a broader understanding of the subject matter across various scientific disciplines. Statins have great potential in the treatment of neurological disorders and neuroprotection and are moving towards customized medicine and personalized therapy.

Keywords

Neurological disorders / Statins / Bibliometric studies / Alzheimer's disease / Multiple sclerosis / Cholesterol / Atorvastatin

Declarations

Not applicable.

Authors' contributions

Yiru Li: Writing - original draft. Chuyuan Yu: Visualization, Data curation. Liling Cui: Visualization, Data curation. Mingcan Xue: Visualization, Data curation. Chenxi Zhang: Writing - original draft, Data curation. Shubin Feng: Conceptualization. Juan Du: Conceptualization. Xinru Xie: Writing - review & editing, Visualization, Software, Formal analysis, Data curation, Conceptualization.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

All the data can be downloaded from PubMed Core Collection.

Funding

This study was funded by the National Natural Science Foundation of China (No.82071390, 82001323, 82101434), Tianjin Key Medical Discipline (Specialty) Construction Project, and the Tianjin Haihe Scholar Health and Wellness Industry High-level Talent Selection and Training Project, Code: TJSHHYXXZ-D2-.

Data availability

All data will be made available on request to the corresponding author. Proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. After approval of a proposal, data will be shared through a secure online platform after the signing of a data access agreement.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We would like to express our sincere gratitude to each author for their valuable contributions to this study.

Authors' other information

Not applicable.

References

[1] Chong PH, Boskovich A, Stevkovic N, et al. Statin-associated peripheral neuropathy: review of the literature. Pharmacotherapy. 2004; 24(9):1194-1203. https://doi.org/10.1592/phco.24.13.1194.38084

[2] Umapathi T, Chaudhry V. Toxic neuropathy. Curr Opin Neurol. 2005; 18(5):574-580. https://doi.org/10.1097/01.wco.0000180158.34713.aa

[3] Morris G, Fernandes BS, Puri BK, et al. Leaky brain in neurological and psychiatric disorders: drivers and consequences. Aust N Z J Psychiatry. 2018; 52(10):924-948. https://doi.org/10.1177/0004867418796955

[4] Peltier AC, Russell JW. Advances in understanding drug-induced neuropathies. Drug Saf. 2006; 29(1):23-30. https://doi.org/10.2165/00002018-200629010-00002

[5] Weimer LH, Sachdev N. Update on medication-induced peripheral neuropathy. Curr Neurol Neurosci Rep. 2009; 9(1):69-75. https://doi.org/10.1007/s11910-009-0011-z

[6] Fracassi A, Marangoni M, Rosso P, et al. Statins and the brain: more than lipid lowering agents. Curr Neuropharmacol. 2019; 17(1):59-83. https://doi.org/10.2174/1570159X15666170703101816

[7] Zhang Q, Dong J, Yu Z. Pleiotropic use of statins as non-lipid-lowering drugs. Int J Biol Sci. 2020; 16(14):2704-2711. https://doi.org/10.7150/ijbs.42965

[8] Chamani S, Mobasheri L, Zerehpoosh S, et al. The effect of statins on the differentiation and function of central nervous system cells. Curr Med Chem. 2024; 31(11):1348-1360. https://doi.org/10.2174/0929867330666230308121645

[9] Kosowski M, Smolarczyk-Kosowska J, Hachuła M, et al. The effects of statins on neurotransmission and their neuroprotective role in neurological and psychiatric disorders. Molecules. 2021; 26(10) https://doi.org/10.3390/molecules26102838

[10] Malfitano AM, Marasco G, Proto MC, et al. Statins in neurological disorders: an overview and update. Pharm Res. 2014; 88:74-83. https://doi.org/10.1016/j.phrs.2014.06.007

[11] Xu X, Gao W, Cheng S, et al. Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury. J Neuroinflamm. 2017; 14(1):167. https://doi.org/10.1186/s12974-017-0934-2

[12] Wang M, Li M, Xie Y. The association between statins exposure and peripheral neuropathy risk: a meta-analysis. J Clin Pharm Ther. 2021; 46(4):1046-1054. https://doi.org/10.1111/jcpt.13393

[13] Ling Q, Tejada-Simon MV. Statins and the brain: new perspective for old drugs. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 66:80-86. https://doi.org/10.1016/j.pnpbp.2015.11.013

[14] Svendsen TK, Krøigård T, Wirenfeldt M, et al. Statin use and peripheral nerve function-A prospective follow-up study. Basic Clin Pharm Toxicol. 2020; 126(3):203-211. https://doi.org/10.1111/bcpt.13320

[15] Schmeer C, Kretz A, Isenmann S. Statin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins. Restor Neurol Neurosci. 2006; 24(2):79-95.

[16] Orr JD. Statins in the spectrum of neurologic disease. Curr Atheroscler Rep. 2008; 10(1):11-18. https://doi.org/10.1007/s11883-008-0003-5

[17] Ninkov A, Frank JR, Maggio LA. Bibliometrics: methods for studying academic publishing. Perspect Med Educ. 2022; 11(3):173-176. https://doi.org/10.1007/s40037-021-00695-4

[18] Sang XZ, Chen W, Hou XX, et al. Association between statin use and dementia, and related mechanisms: a bibliometric analysis from 2007 to 2023. J Alzheimers Dis. 2024; 101(3):847-876. https://doi.org/10.3233/JAD-240270

[19] Lei Q, Peng WN, You H, et al. Statins in nervous system-associated diseases: angels or devils. Pharmazie. 2014; 69(6):448-454.

[20] Coulson WF. Statin neuropathy. J Fam Pr. 2011; 60(4):182-184.

[21] Rajanikant GK, Zemke D, Kassab M, et al. The therapeutic potential of statins in neurological disorders. Curr Med Chem. 2007; 14(1):103-112. https://doi.org/10.2174/092986707779313462

[22] Collins R, Armitage J, Parish S, et al. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004; 363(9411):757-767. https://doi.org/10.1016/S0140-6736(04)15690-0

[23] Mann CM, Lee JH, Hillyer J, et al. Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury. Exp Neurol. 2010; 221(2):285-295. https://doi.org/10.1016/j.expneurol.2009.11.006

[24] Reiss AB, Wirkowski E. Role of HMG-CoA reductase inhibitors in neurological disorders: progress to date. Drugs. 2007; 67(15):2111-2120. https://doi.org/10.2165/00003495-200767150-00001

[25] Otruba P, Kanovsky P, Hlustik P. Treatment with statins and peripheral neuropathy: results of 36-months a prospective clinical and neurophysiological follow-up. Neuro Endocrinol Lett. 2011; 32(5):688-690.

[26] Chun HJ, Kim DW, Yi HJ, et al. Effects of statin and deferoxamine administration on neurological outcomes in a rat model of intracerebral hemorrhage. Neurol Sci. 2012; 33(2):289-296. https://doi.org/10.1007/s10072-011-0733-y

[27] Weber MS, Youssef S, Dunn SE, et al. Statins in the treatment of central nervous system autoimmune disease. J Neuroimmunol. 2006; 178(1-2):140-148. https://doi.org/10.1016/j.jneuroim.2006.06.006

[28] Desai R, Campanella M. Exploring mitochondrial cholesterol signalling for therapeutic intervention in neurological conditions. Br J Pharm. 2019; 176(22):4284-4292. https://doi.org/10.1111/bph.14697

[29] Amanlou A, Nassireslami E, Dehpour AR, et al. Beneficial effects of statins on seizures independent of their Lipid-Lowering effect: a narrative review. Iran J Med Sci. 2023; 48(1):13-25. https://doi.org/10.30476/IJMS.2021.91645.2289

[30] Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006; 97(8A) https://doi.org/10.1016/j.amjcard.2005.12.010

[31] Bifulco M, Malfitano AM, Marasco G. Potential therapeutic role of statins in neurological disorders. Expert Rev Neurother. 2008; 8(5):827-837. https://doi.org/10.1586/14737175.8.5.827

[32] Zamami Y, Niimura T, Kawashiri T, et al. Identification of prophylactic drugs for oxaliplatin-induced peripheral neuropathy using big data. Biomed Pharm. 2022; 148:112744. https://doi.org/10.1016/j.biopha.2022.112744

[33] Menge T, Hartung HP, Stüve O. Statins-a cure-all for the brain. Nat Rev Neurosci. 2005; 6(4):325-331. https://doi.org/10.1038/nrn1652

[34] Hendrix S, Nitsch R. The role of t helper cells in neuroprotection and regeneration. J Neuroimmunol. 2007; 184(1-2):100-112. https://doi.org/10.1016/j.jneuroim.2006.11.019

[35] Pasha R, Azmi S, Ferdousi M, et al. Lipids, Lipid-Lowering therapy, and neuropathy: a narrative review. Clin Ther. 2022; 44(7):1012-1025. https://doi.org/10.1016/j.clinthera.2022.03.013

[36] Torrandell-Haro G, Branigan GL, Vitali F, et al. Statin therapy and risk of alzheimer's and age-related neurodegenerative diseases. Alzheimers Dement. 2020; 6(1):e12108. https://doi.org/10.1002/trc2.12108

[37] Jeong SH, Lee HS, Chung SJ, et al. Effects of statins on dopamine loss and prognosis in parkinson's disease. Brain. 2021; 144(10):3191-3200. https://doi.org/10.1093/brain/awab292

[38] Oveisgharan S, Yu L, Barnes LL, et al. Association of statins with cerebral atherosclerosis and incident parkinsonism in older adults. Neurology. 2022; 98(19):e1976-e1984. https://doi.org/10.1212/WNL.0000000000200182

[39] Elsais A, Lund C, Kerty E. Ptosis, diplopia and statins: an association. Eur J Neurol. 2008; 15(10):e92-e93. https://doi.org/10.1111/j.1468-1331.2008.02234.x

[40] Thompson PD, Panza G, Zaleski A, et al. Statin-Associated side effects. J Am Coll Cardiol. 2016; 67(20):2395-2410. https://doi.org/10.1016/j.jacc.2016.02.071

[41] Vance JE. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Model Mech. 2012; 5(6):746-755. https://doi.org/10.1242/dmm.010124

[42] Ibáñez Pérez de la Blanca MA. Antithrombotic and risk of hemorrhagic complications in over-60-year-olds after mild-minimal traumatic brain injury. Brain Inj. 2023; 37(12-14):1355-1361. https://doi.org/10.1080/02699052.2023.2284907

[43] Brondino N, Emanuele E, Geroldi D. Caution on the potential usefulness of statins in neuropsychiatric diseases. Med Hypotheses. 2007; 69(3):697. https://doi.org/10.1016/j.mehy.2007.01.020

[44] Formaglio M, Vial C. Statin induced neuropathy: myth or reality? Rev Neurol. 2006; 162(12):1286-1289. https://doi.org/10.1016/s0035-3787(06)75148-7

[45] Lashgari NA, Roudsari NM, Zadeh S, et al. Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases. Inflammopharmacology. 2023; 31(1):57-75. https://doi.org/10.1007/s10787-022-01077-w

[46] Aizawa F, Kajimoto H, Okabayashi A, et al. Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione S-transferase. Neurochem Int. 2024; 180:105863. https://doi.org/10.1016/j.neuint.2024.105863

[47] Nabavi SM, Ahmed T, Nawaz M, et al. Targeting STATs in neuroinflammation: the road less traveled. Pharm Res. 2019; 141:73-84. https://doi.org/10.1016/j.phrs.2018.12.004

[48] Fujimoto T, Morofuji Y, Kovac A, et al. Pitavastatin ameliorates Lipopolysaccharide-Induced Blood-Brain barrier dysfunction. Biomedicines. 2021; 9(7) https://doi.org/10.3390/biomedicines9070837

[49] Bifulco M, Malfitano AM, Marasco G. Potential therapeutic role of statins in neurological disorders. Expert Rev Neurother. 2008; 8(5):827-837. https://doi.org/10.1586/14737175.8.5.827

[50] Tierney EF, Thurman DJ, Beckles GL, et al. Association of statin use with peripheral neuropathy in the U.S. Population 40 years of age or older. J Diabetes. 2013; 5(2):207-215. https://doi.org/10.1111/1753-0407.12013

[51] Heyer EJ, Mergeche JL, Bruce SS, et al. Statins reduce neurologic injury in asymptomatic carotid endarterectomy patients. Stroke. 2013; 44(4):1150-1152. https://doi.org/10.1161/STROKEAHA.111.000362

[52] Petek B, Villa-Lopez M, Loera-Valencia R, et al. Connecting the brain cholesterol and renin-angiotensin systems: potential role of statins and RAS-modifying medications in dementia. J Intern Med. 2018; 284(6):620-642. https://doi.org/10.1111/joim.12838

[53] Carroll CB, Wyse R, Grosset DG. Statins and parkinson's: a complex interaction. Mov Disord. 2019; 34(7):934-935. https://doi.org/10.1002/mds.27721

[54] Komatsu R, Yilmaz HO, You J, et al. Lack of association between preoperative statin use and respiratory and neurologic complications after cardiac surgery. Anesthesiology. 2017; 126(5):799-809. https://doi.org/10.1097/ALN.0000000000001569

[55] Gluhovschi G, Gluhovschi C, Bob F, et al. Multiorgan-protective actions of blockers of the renin-angiotensin system, statins and erythropoietin: common pleiotropic effects in reno-, cardio- and neuroprotection. Acta Clin Belg. 2008; 63(3):152-169. https://doi.org/10.1179/acb.2008.026

[56] Wuerch E, Urgoiti GR, Yong VW. The promise of niacin in neurology. Neurotherapeutics. 2023; 20(4):1037-1054. https://doi.org/10.1007/s13311-023-01376-2

[57] Ravnskov U, Rosch PJ, Sutter MC, et al. Should we lower cholesterol as much as possible. BMJ. 2006; 332(7553):1330-1332. https://doi.org/10.1136/bmj.332.7553.1330

[58] Corrao G, Zambon A, Bertù L, et al. Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated databases. J Epidemiol Community Health. 2004; 58(12):1047-1051. https://doi.org/10.1136/jech.2003.013409

[59] Brass LM, Alberts MJ, Sparks L, et al. An assessment of statin safety by neurologists. Am J Cardiol. 2006; 97(8A) https://doi.org/10.1016/j.amjcard.2005.12.017

[60] Catalano M, Ramello M, Conca R, et al. Risk factors for Nab-Paclitaxel and Gemcitabine-Induced peripheral neuropathy in patients with pancreatic cancer. Oncology. 2022; 100(7):384-391. https://doi.org/10.1159/000524868

[61] Brownrigg JR, de Lusignan S, McGovern A, et al. Peripheral neuropathy and the risk of cardiovascular events in type 2 diabetes mellitus. Heart. 2014; 100(23):1837-1843. https://doi.org/10.1136/heartjnl-2014-305657

[62] Davis TM, Yeap BB, Davis WA, et al. Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the fremantle diabetes study. Diabetologia. 2008; 51(4):562-566. https://doi.org/10.1007/s00125-007-0919-2

[63] Uwah AN, Ackler J, Leighton JC, et al. The effect of diabetes on oxaliplatin-induced peripheral neuropathy. Clin Colorectal Cancer. 2012; 11(4):275-279. https://doi.org/10.1016/j.clcc.2012.05.002

[64] Scicchitano F, Constanti A, Citraro R, et al. Statins and epilepsy: preclinical studies, clinical trials and statin-anticonvulsant drug interactions. Curr Drug Targets. 2015; 16(7):747-756. https://doi.org/10.2174/1389450116666150330114850

[65] Arjmand B, Dehghanbanadaki H, Yoosefi M, et al. Association of plasma acylcarnitines and amino acids with hypertension: a nationwide metabolomics study. PLoS One. 2023; 18(1):e0279835. https://doi.org/10.1371/journal.pone.0279835

[66] He J, Ren M, Li H, et al. Exosomal circular RNA as a biomarker platform for the early diagnosis of Immune-Mediated demyelinating disease. Front Genet. 2019; 10:860. https://doi.org/10.3389/fgene.2019.00860

[67] López-Farré AJ, Zamorano-León JJ, Segura A, et al. Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke. J Neurochem. 2012; 121(2):314-325. https://doi.org/10.1111/j.1471-4159.2012.07683.x

[68] Chen H, Clifford DB, Deng L, et al. Peripheral neuropathy in ART-experienced patients: prevalence and risk factors. J Neurovirol. 2013; 19(6):557-564. https://doi.org/10.1007/s13365-013-0216-4

[69] Harvey PD, Sabbagh MN, Harrison JE, et al. No evidence of neurocognitive adverse events associated with alirocumab treatment in 3340 patients from 14 randomized phase 2 and 3 controlled trials: a meta-analysis of individual patient data. Eur Heart J. 2018; 39(5):374-381. https://doi.org/10.1093/eurheartj/ehx661

[70] Keyrouz SG, Diringer MN. Year in review 2011. Crit CareNeurocritical Care Crit Care. 2012; 16(6):245. https://doi.org/10.1186/cc11825