Association of APOE Gene Variants with Cognitive Dysfunction in Polycystic Ovary Syndrome
Downloads
Objective: To investigate the relationship between APOE polymorphisms and cognitive function in PCOS women and identify potential genetic biomarkers for cognitive risk stratification.
Methods and Materials: This cross-sectional study included 120 women with PCOS. Hormonal profiling (FSH, LH, total and free testosterone), metabolic parameters (insulin, HbA1c, HOMA-IR), and cognitive assessment using Montreal Cognitive Assessment (MoCA) were performed. APOE gene polymorphisms were analyzed to determine epsilon genotypes. Statistical analyses were performed by using SPSS software version 25.0 (SPSS, Chicago). Continuous data were presented as mean and standard deviation, and analyzed with Student t-test. Categorical variables were expressed as number and percentage and analyzed with Chi-square test. Binary logistic regression was used to determine the association between APOE gene polymorphism and cognitive impairment.
Findings: PCOS patients with cognitive impairment were older with lower educational levels, demonstrating significantly higher testosterone, insulin levels, and HOMA-IR values. MoCA cognitive domains showed significant impairment. APOE epsilon genotype analysis revealed significant associations with cognitive status (p=0.022). The ε3ε3 genotype was more prevalent in cognitively intact PCOS, while ε2ε3 and ε3ε4 genotypes were significantly more frequent in cognitively impaired PCOS (p=0.030 and p=0.040, respectively). ε2ε3 carriers had 3.61-fold increased odds of cognitive impairment (95% CI: 1.14-11.5), while ε3ε4 carriers had 3.05-fold increased risk (95% CI: 1.05-8.81) compared to ε3ε3 carriers.
Conclusion: This study demonstrates significant associations between APOE polymorphisms and cognitive function in PCOS patients. Both ε2ε3 and ε3ε4 genotypes confer increased cognitive impairment risk, while ε3ε3 appears protective. APOE genotyping could serve as a valuable tool for cognitive risk stratification in PCOS management after further validation.
Downloads
Berlau, D. J., Corrada, M. M., Head, E., & Kawas, C. H. (2009). APOE ε2 is associated with intact cognition but increased Alzheimer pathology in the oldest old. Neurology, 72(9), 829-834. https://doi.org/10.1212/01.wnl.0000343853.00346.a4
Berlau, D. J., Kahle-Wrobleski, K., & Head, E. (2007). Dissociation of neuropathologic findings and cognition: case report of an apolipoprotein E ε2/ε2 genotype. Arch Neurol, 64(8), 1193-1196. https://doi.org/10.1001/archneur.64.8.1193
Castellano, C. A., Baillargeon, J. P., & Nugent, S. (2015). Regional brain glucose hypometabolism in young women with polycystic ovary syndrome: possible link to mild insulin resistance. PLoS One, 10(12), e0144116. https://doi.org/10.1371/journal.pone.0144116
Christ, J. P., & Cedars, M. I. (2023). Current guidelines for diagnosing PCOS. Diagnostics (Basel), 13(6), 1113. https://doi.org/10.3390/diagnostics13061113
Cordeiro, A., Gomes, C., Bicker, J., & Fortuna, A. (2024). Aging and cognitive resilience: molecular mechanisms as new potential therapeutic targets. Drug Discov Today, 29(8), 104093. https://doi.org/10.1016/j.drudis.2024.104093
Correa, D. D., Satagopan, J., & Baser, R. E. (2014). APOE polymorphisms and cognitive functions in patients with brain tumors. Neurology, 83(4), 320-327. https://doi.org/10.1212/WNL.0000000000000617
Gharbi-Meliani, A., Dugravot, A., & Sabia, S. (2021). The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study. Alzheimers Res Ther, 13(1), 18. https://doi.org/10.1186/s13195-020-00740-0
Guoqing, Z., Fang, S., & Lihui, D. (2016). Cerebral white matter lesions and silent cerebral infarcts in postmenopausal women with polycystic ovary syndrome. Gynecol Endocrinol, 32(8), 655-658. https://doi.org/10.1080/09513590.2016.1177013
Huddleston, H. G., Jaswa, E. G., & Casaletto, K. B. (2024). Associations of polycystic ovary syndrome with indicators of brain health at midlife in the CARDIA cohort. Neurology, 102(1), e208104. https://doi.org/10.1212/WNL.0000000000208104
Jarrett, B. Y., Vantman, N., & Mergler, R. J. (2019). Dysglycemia, not altered sex steroid hormones, affects cognitive function in polycystic ovary syndrome. J Endocr Soc, 3(8), 1858-1868. https://doi.org/10.1210/js.2019-00116
Johnson, L. A., Torres, E. R. S., Impey, S., Stevens, J. F., & Raber, J. (2017). Apolipoprotein E4 and insulin resistance interact to impair cognition and alter the epigenome and metabolome. Sci Rep, 7(1), 43701. https://doi.org/10.1038/srep43701
Lacey, C., Paterson, T., Gawryluk, J. R., & Alzheimer's Disease Neuroimaging, I. (2024). Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: a VBM and DTI replication study. PLoS One, 19(1), e0292576. https://doi.org/10.1371/journal.pone.0292576
Li, G., Hu, J., & Zhang, S. (2020). Changes in resting-state cerebral activity in women with polycystic ovary syndrome: a functional MR imaging study. Front Endocrinol (Lausanne), 11, 603279. https://doi.org/10.3389/fendo.2020.603279
Livingston, G., Huntley, J., & Sommerlad, A. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 396(10248), 413-446. https://doi.org/10.1016/S0140-6736(20)30367-6
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., & Charbonneau, S. (2005). The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc, 53(4), 695-699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Naz, M. S., Rahnemaei, F. A., & Tehrani, F. R. (2023). Possible cognition changes in women with polycystic ovary syndrome: a narrative review. Obstet Gynecol Sci, 66(5), 347-363. https://doi.org/10.5468/ogs.23042
Neergaard, J. S., Dragsbæk, K., & Christiansen, C. (2017). Metabolic syndrome, insulin resistance, and cognitive dysfunction: does your metabolic profile affect your brain? Diabetes, 66(7), 1957-1963. https://doi.org/10.2337/db16-1444
Nelson, P. T., Pious, N. M., & Jicha, G. A. (2013). APOE-ε2 and APOE-ε4 correlate with increased amyloid accumulation in cerebral vasculature. J Neuropathol Exp Neurol, 72(7), 708-715. https://doi.org/10.1097/NEN.0b013e31829a25b9
O'Donoghue, M. C., Murphy, S. E., Zamboni, G., Nobre, A. C., & Mackay, C. E. (2018). APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: a review. Cortex, 104, 103-123. https://doi.org/10.1016/j.cortex.2018.03.025
Rees, D. A., Udiawar, M., Berlot, R., Jones, D. K., & O'Sullivan, M. J. (2016). White matter microstructure and cognitive function in young women with polycystic ovary syndrome. J Clin Endocrinol Metab, 101(1), 314-323. https://doi.org/10.1210/jc.2015-2318
Saddiki, H., Fayosse, A., & Cognat, E. (2020). Age and the association between apolipoprotein E genotype and Alzheimer disease: a cerebrospinal fluid biomarker-based case-control study. PLoS Med, 17(11), e1003289. https://doi.org/10.1371/journal.pmed.1003289
Salcedo-Tello, P., Ortiz-Matamoros, A., & Arias, C. (2011). GSK3 function in the brain during development, neuronal plasticity, and neurodegeneration. Int J Alzheimers Dis, 189728. https://doi.org/10.4061/2011/189728
Spinelli, M., Fusco, S., & Grassi, C. (2019). Brain insulin resistance and hippocampal plasticity: mechanisms and biomarkers of cognitive decline. Front Neurosci, 13, 788. https://doi.org/10.3389/fnins.2019.00788
Sukhapure, M., Eggleston, K., Douglas, K., Fenton, A., Frampton, C., & Porter, R. J. (2022). Free testosterone is related to aspects of cognitive function in women with and without polycystic ovary syndrome. Arch Womens Ment Health, 25(1), 87-94. https://doi.org/10.1007/s00737-021-01175-8
Wadhwani, A. R., Affaneh, A., Van Gulden, S., & Kessler, J. A. (2019). Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease. Ann Neurol, 85(5), 726-739. https://doi.org/10.1002/ana.25455
Wang, J. Y., Zhang, L., Liu, J., Yang, W., & Ma, L. N. (2021). Metabolic syndrome, ApoE genotype, and cognitive dysfunction in an elderly population: a single-center, case-control study. World J Clin Cases, 9(5), 1005-1015. https://doi.org/10.12998/wjcc.v9.i5.1005
Yi, D., Lee, Y., & Byun, M. S. (2018). Synergistic interaction between APOE and family history of Alzheimer's disease on cerebral amyloid deposition and glucose metabolism. Alzheimers Res Ther, 10(1), 84. https://doi.org/10.1186/s13195-018-0411-x
Yu, L., Boyle, P. A., & Nag, S. (2015). APOE and cerebral amyloid angiopathy in community-dwelling older persons. Neurobiol Aging, 36(11), 2946-2953. https://doi.org/10.1016/j.neurobiolaging.2015.07.031
Copyright (c) 2025 International Journal of Body, Mind and Culture
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
