COGNITIVE DYSFUNCTION IN SUBCLINICAL HYPOTHYROIDISM USING AUDITORY P300 EVOKED POTENTIALS-SYSTEMATIC REVIEW AND META-ANALYSIS

KRISHNAMURTHY SOUNDARIYA; REENAA MOHAN; JENIFER FLORENCE MARY; DEEPIKA VELUSAMI

doi:10.22159/ajpcr.2025v18i6.54545

Authors

KRISHNAMURTHY SOUNDARIYA Department of Physiology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India https://orcid.org/0000-0002-7244-8811
REENAA MOHAN Department of Community Medicine, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India. https://orcid.org/0000-0002-8405-1897
JENIFER FLORENCE MARY Department of Community Medicine, Mahatma Gandhi Medical College and Research Institute, SBV (Deemed to be University), Puducherry, India https://orcid.org/0000-0001-8869-2416
DEEPIKA VELUSAMI Department of Physiology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India

DOI:

https://doi.org/10.22159/ajpcr.2025v18i6.54545

Keywords:

Subclinical hypothyroidism, P300, Cognition, Evoked potentials

Abstract

Subclinical hypothyroidism, an early and mild form of hypothyroidism rarely presents with clinical manifestations. Literature search has revealed conflicting results on cognitive dysfunction in subclinical hypothyroidism. While the majority of studies used neuropsychiatric tests for cognitive assessment, we aimed to study the cognitive function in subclinical hypothyroidism using evoked potentials “P300.” The data sources used were Google Scholar, PubMed, MEDLINE, and Cochrane which were rigorously searched until March 2024. The meta-analysis includes all published studies that used P300 evoked potential to assess cognitive performance in subclinical hypothyroidism. A specified checklist supervised the data extraction process. Using RevMan 5 software, mean P300 at Cz values were aggregated from the chosen trials. The differences in P300 at Cz between normal and subclinical hypothyroidism were evaluated. Data analyses were conducted till March 2023. The current meta-analysis was done using 4 studies with 156 subjects with subclinical hypothyroidism and 182 apparently healthy subjects showed a significant increase in P300 latency in subclinical hypothyroidism (mean difference (MD)=21.65, 95% confidence interval [CI] 0.37–42.92, p<0.00001) at Cz. There was a significant decrease in P300 amplitude in subclinical hypothyroidism compared to healthy subjects at Cz (MD=−0.31, 95% CI −1.08 −0.47, p<0.33). Our study results suggest that subclinical hypothyroidism is associated with cognitive dysfunction as evidenced by the prolongation of the P300 latency. However, there is a need for analysis of more prospective cohort studies.

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Author Biography

JENIFER FLORENCE MARY, Department of Community Medicine, Mahatma Gandhi Medical College and Research Institute, SBV (Deemed to be University), Puducherry, India

References

Vanderpump MP. Epidemiology of thyroid disorders. In: Luster M, Duntas LH, Wartofsky L, editors. The Thyroid and its Diseases: A Comprehensive Guide for the Clinician. Cham: Springer International Publishing; 2019. p. 75-85. doi: 10.1007/978-3-319-72102-6_6

Behera BP, Sen RK. A study on the prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus in a tertiary centre in a tribal population of eastern India. Int J Pharm Pharm Sci. 2023;15(6):29-34. doi: 10.22159/ijpps.2023v15i6.48019

Kumar S, Gupta RC. Prevalence of subclinical hypothyroidism in general adult population of Northern India. J Med Sci Clin Res. 2020;8(3):595-597. doi: 10.18535/jmscr/v8i3.103

Raza SA, Mahmood N. Subclinical hypothyroidism: Controversies to consensus. Indian J Endocrinol Metab. 2013 Dec;17(Suppl 3):S636-S642. doi: 10.4103/2230-8210.123555, PMID 24910826

Samuels MH. Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):377-383. doi: 10.1097/MED.0000000000000089, PMID 25122491

Ye Y, Wang Y, Li S, Guo J, Ding L, Liu M. Association of hypothyroidism and the risk of cognitive dysfunction: A meta-analysis. J Clin Med. 2022;11(22):6726. doi: 10.3390/jcm11226726, PMID 36431204

Akintola AA, Jansen SW, Van Bodegom D, Van Der Grond J, Westendorp RG, De Craen AJ, et al. Subclinical hypothyroidism and cognitive function in people over 60 years: A systematic review and meta-analysis. Front Aging Neurosci. 2015;7:150. doi: 10.3389/ fnagi.2015.00150, PMID 26321946

Pasqualetti G, Pagano G, Rengo G, Ferrara N, Monzani F. Subclinical hypothyroidism and cognitive impairment: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(11):4240-4248. doi: 10.1210/jc.2015-2046, PMID 26305618

Devenney E, Hodges JR. The mini-mental state examination: Pitfalls and limitations. Pract Neurol. 2017;17(1):79-80. doi: 10.1136/ practneurol-2016-001520, PMID 27903765

Sur S, Sinha VK. Event-related potential: An overview. Ind Psychiatry J. 2009;18(1):70-73. doi: 10.4103/0972-6748.57865, PMID 21234168

Demirayak P, Kıyı İ, İşbitiren YÖ, Yener G. Cognitive load associates prolonged P300 latency during target stimulus processing in individuals with mild cognitive impairment. Sci Rep. 2023;13(1):15956. doi: 10.1038/s41598-023-43132-8, PMID 37743392

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/ bmj.n71, PMID 33782057

Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. doi: 10.1186/s13643-016-0384-4, PMID 27919275

RevMan 5. Available from: https://training.cochrane.org/online-learning/core-software/revman/revman-5-download [Last accessed on 2024 Feb 20]

Santos WM, Secoli SR, Püschel VA. The Joanna Briggs institute approach for systematic reviews. Rev Lat Am Enfermagem. 2018;26:e3074. doi: 10.1590/1518-8345.2885.3074, PMID 30462787

Mahaur R, Mahajan AS, Jain AK, Singh T, Dhanwal DK, Gupta M. Role of event-related potentials in evaluation of cognitive function in subclinical hypothyroid patients. MAMC J Med Sci. 2016;2(1):43-47. doi: 10.4103/2394-7438.174838

Sivakumar S, Rekha A. Evaluation of cognitive function in subclinical hypothyroidism. Indian J Basic Appl Med Res. 2016;6(1):336-342.

Sharma K, Behera JK, Sood S, Rajput R, Satpal, Praveen P. Study of cognitive functions in newly diagnosed cases of subclinical and clinical hypothyroidism. J Nat Sci Biol Med. 2014;5(1):63-66. doi: 10.4103/0976-9668.127290, PMID 24678200

Paladugu S, Hanmayyagari BR, Kudugunti N, Reddy R, Sahay R, Ramesh J. Improvement in subclinical cognitive dysfunction with thyroxine therapy in hypothyroidism: A study from tertiary care center. Indian J Endocrinol Metab. 2015;19(6):829-833. doi: 10.4103/2230- 8210.167547, PMID 26693436

Dejanovic M, Ivetić V, Nestorović V, Milanović Z, Biševac B, Miletić M, et al. P300 event related potential application to cognitive status assessment of the patients with subclinical hypothyroidism. Prax Med. 2015;44(2):97-102. doi: 10.5937/pramed1502097D

Kocaaslan Atli S, Olgaç Dündar N, Bayazit O, Evirgen Esin N, Erdoğan U, Çatli G, et al. Auditory event-related potentials demonstrate early cognitive impairment in children with subclinical hypothyroidism. J Pediatr Endocrinol Metab. 2019;32(7):689-697. doi: 10.1515/jpem- 2018-0463, PMID 31194683

Tu MC, Lo CP, Chen CY. Vitamin B12 deficiency: Cognitive impairment and neuroimaging correlates. Neuropsychiatry (Lond). 2016;6(6):303-307.

Polich J. Updating P300: An integrative theory of P3a and P3b. Clin Neurophysiol. 2007;118(10):2128-2148. doi: 10.1016/j.

clinph.2007.04.019, PMID 17573239

Snyder E, Hillyard SA. Long-latency evoked potentials to irrelevant, deviant stimuli. Behav Biol. 1976;16(3):319-331. doi: 10.1016/s0091- 6773(76)91447-4, PMID 1275853

Bennys K, Portet F, Touchon J, Rondouin G. Diagnostic value of event-related evoked potentials N200 and P300 subcomponents in early diagnosis of Alzheimer’s disease and mild cognitive impairment. J Clin Neurophysiol. 2007 Oct;24(5):405-412. doi: 10.1097/ WNP.0b013e31815068d5, PMID 17912065

Han SH, Jeong HB, Park KY, Shin HW, Youn YC, Kim S. P300 latency changes in patients with mild cognitive impairment after taking choline alphoscerate; a preliminary study. eNeurologicalSci. 2018 Apr 12;11:5-8. doi: 10.1016/j.ensci.2018.04.004, PMID 29928709

Rieben C, Segna D, Da Costa BR, Collet TH, Chaker L, Aubert CE, et al. Subclinical thyroid dysfunction and the risk of cognitive decline: A meta-analysis of prospective cohort studies. J Clin Endocrinol Metab. 2016;101(12):4945-4954. doi: 10.1210/jc.2016- 2129, PMID 27689250

Pyun JM, Park YH, Kim S. Subclinical hypothyroidism and cognitive impairment. J Alzheimers Dis. 2022;88(2):757-762. doi: 10.3233/JAD- 220302, PMID 35694927

Hebbar H, Kumar S, Amin S, Doizode S. Subclinical hypothyroidism in pregnancy; is there a need for pharmacological intervention. Int J Pharm Pharm Sci. 2017;9(3):186-191. doi: 10.22159/ijpps.2017v9i3.16542

Correia N, Mullally S, Cooke G, Tun TK, Phelan N, Feeney J, et al. Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism. J Clin Endocrinol Metab. 2009 Oct;94(10):3789-397. doi: 10.1210/jc.2008-2702, PMID 19584178

Miranda EC, Pinheiro MM, Pereira LD, Iorio MC. Correlation of the P300 evoked potential in depressive and cognitive aspects of aging. Braz J Otorhinolaryngol. 2012 Oct;78(5):83-89. doi: 10.5935/1808- 8694.20120013, PMID 23108825

Pavarini SC, Brigola AG, Luchesi BM, Souza ÉN, Rossetti ES, Fraga FJ, et al. On the use of the P300 as a tool for cognitive processing assessment in healthy aging: A review. Dement Neuropsychol. 2018 Jan-Mar;12(1):1-11. doi: 10.1590/1980-57642018dn12-010001, PMID 29682227

Eslami-Amirabadi M, Sajjadi SA. The relation between thyroid dysregulation and impaired cognition/behaviour: An integrative review. J Neuroendocrinol. 2021 Mar;33(3):e12948. doi: 10.1111/jne.12948, PMID 33655583