Beta-blockers in elderly patients: neuroprotective effect or risk of cognitive decline?

Abstract

BACKGROUND: Due to the fact that the number of elderly people with cognitive disorders is steadily increasing worldwide, there is an increased interest in studying the effects of drugs of different pharmacological groups on cognitive function.

For many years, beta-blockers have been one of the main groups in the therapy of cardiovascular diseases. The effect of beta-blockers on cognitive function has been studied for a long time, and there is different, sometimes contradictory data on this issue.

AIM: To evaluate the incidence of cognitive impairment in elderly and to determine the associations between cognitive impairment and the beta-blockers use.

MATERIALS AND METHODS: Cross-sectional study included all patients aged 60 years and older who attended the ambulance care from 24.10.2019 to 15.12.2019 at the polyclinic No. 78 in Saint Petersburg.

Measurements: the Montreal cognitive assessment (MoCA) test, the 15-item Geriatric Depression Scale. Data collection included a full medical history, a medication review and questionnaire.

RESULTS: The prevalence of cognitive impairment among the study participants was 71.1% (n = 138). Сognitive impairment was associated with high blood pressure and a history of stroke (p < 0.05). Beta-blockers use was associated with decreased in total MoCA score, fluency (p = 0.0115), thinking (p = 0.0012), and memory (p = 0.0040). The identified association remained statistically significant after adjusting for gender, age, high blood pressure, a history of stroke, level of education, and decreased emotional background with odds ratio 2.245 (95% confidence interval 1.156–4.358) for the fluency test and coefficient of regression −0.781 (95% confidence interval [−1,233]–[−0,328]) for delayed memory.

CONCLUSIONS: Memory impairment (coefficient of regression −0.781, 95% confidence interval −1.233 to −0.328) and decreased fluency (odds ratio 2.245; 95% confidence interval 1.156–4.358) were observed in the study in the outpatient elderly patient population taking beta-blockers. The beta-blockers may lead to memory impairment. When choosing hypotensive therapy, all possible effects of beta-blockers should be considered, including the effect on cognitive status.

Keywords

elderly / cognitive disorders / dementia / antihypertensive medication / beta-blockers

References

[1] Pharmacotherapy in the elderly and senile: methodological guidelines. Available from: https://rgnkc.ru/images/metod_materials/Farmakoterapiya_2018.pdf. Accessed: June 15, 2022. (In Russ.)

[2] Фармакотерапия у лиц пожилого и старческого возраста: методические руководства. Режим доступа: https://rgnkc.ru/images/metod_materials/Farmakoterapiya_2018.pdf. Дата обращения: 15.06.2022.

[3] 1. Tkacheva O. N., Nedogoda S.V. Pharmacotherapy in the elderly and elderly: methodological guidelines /M., 2018. - 2018.

[4] Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699. DOI: 10.1111/j.1532-5415.2005.53221.x

[5] Nasreddine Z.S., Phillips N.A., Bédirian V. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment // J. Am. Geriatr. Soc. 2005. Vol. 53, No. 4. P. 695–699. DOI: 10.1111/j.1532-5415.2005.53221.x

[6] 2. Nasreddine ZS, Phillips NA, Bédirian V et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr; 53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

[7] Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37–49. DOI: 10.1016/0022-3956(82)90033-4

[8] Yesavage J.A., Brink T.L., Rose T.L. et al. Development and validation of a geriatric depression screening scale: a preliminary report // J. Psychiatr. Res. 1982. Vol. 17, No. 1. P. 37–49. DOI: 10.1016/0022-3956(82)90033-4

[9] 3. Yesavage JA, Brink TL, Rose TL等人，老年抑郁症筛查量表的开发和验证：初步报告。J Psychiatr Res. 1982-1983;17(1):37-49. doi: 10.1016/0022-3956(82)90033-4.

[10] Sierra C. Hypertension and the risk of dementia. Front Cardiovasc Med. 2020;7:5. DOI: 10.3389/fcvm.2020.00005

[11] Sierra C. Hypertension and the risk of dementia // Front. Cardiovasc. Med. 2020. Vol. 7. P. 5. DOI: 10.3389/fcvm.2020.00005

[12] 4. Sierra C. 高血压与痴呆症的风险。Front Cardiovasc Med. 2020;7:5. 2020年1月31日发表。DOI:10.3389/fcvm.2020.00005。

[13] Gelber RP, Ross GW, Petrovitch H, et al. Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study. Neurology. 2013;81(10):888–895. DOI: 10.1212/WNL.0b013e3182a351d4

[14] Gelber R.P., Ross G.W., Petrovitch H. et al. Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study // Neurology. 2013. Vol. 81, No. 10. P. 888–895. DOI: 10.1212/WNL.0b013e3182a351d4

[15] 5.Gelber RP, Ross GW, Petrovitch H, Masaki KH, Launer LJ, White LR. 抗高血压药物的使用和认知障碍的风险：檀香山-亚洲老龄化研究。Neurology. 2013;81(10):888-895. doi:10.1212/WNL.0b013e3182a351d4

[16] Moretti R, Torre P, Antonello RM, et al. Risk factors for vascular dementia: hypotension as a key point. Vasc Health Risk Manag. 2008;4(2):395–402. DOI: 10.2147/vhrm.s2434

[17] Moretti R., Torre P., Antonello R.M. et al. Risk factors for vascular dementia: hypotension as a key point // Vasc. Health Risk Manag. 2008. Vol. 4, No. 2. P. 395–402. DOI: 10.2147/vhrm.s2434

[18] 6.Moretti R, Torre P, Antonello RM, Manganaro D, Vilotti C, Pizzolato G. 血管性痴呆的风险因素：低血压是关键。Vasc Health Risk Manag. 2008;4(2):395-402. doi:10.2147/vhrm.s2434

[19] Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009;10(3):211–223. DOI: 10.1038/nrn2573

[20] Sara S.J. The locus coeruleus and noradrenergic modulation of cognition // Nat. Rev. Neurosci. 2009. Vol. 10, No. 3. P. 211–223. DOI: 10.1038/nrn2573

[21] 7.Sara SJ. 定位器和认知的去甲肾上腺素能调节。Nat Rev Neurosci. 2009;10(3):211-223. doi:10.1038/nrn2573

[22] Paredes DA, Cartford MC, Catlow BJ, et al. Neurotransmitter release during delay eyeblink classical conditioning: role of norepinephrine in consolidation and effect of age. Neurobiol Learn Mem. 2009;92(3):267–282. DOI: 10.1016/j.nlm.2008.08.008

[23] Paredes D.A., Cartford M.C., Catlow B.J. et al. Neurotransmitter release during delay eyeblink classical conditioning: role of norepinephrine in consolidation and effect of age // Neurobiol. Learn. Mem. 2009. Vol. 92, No. 3. P. 267–282. DOI: 10.1016/j.nlm.2008.08.008

[24] 8.Paredes DA, Cartford MC, Catlow BJ, et al. 古典条件下延迟眨眼的神经递质释放：去甲肾上腺素在巩固和影响中的作用

[25] Arrieta-Cruz I, Wang J, Pavlides C, Pasinetti GM. Carvedilol reestablishes long-term potentiation in a mouse model of Alzheimer’s disease. J Alzheimers Dis. 2010;21(2):649–654. DOI: 10.3233/JAD-2010-100225

[26] Arrieta-Cruz I., Wang J., Pavlides C., Pasinetti GM. Carvedilol reestablishes long-term potentiation in a mouse model of Alzheimer’s disease // J. Alzheimers Dis. 2010. Vol. 21, No. 2. P. 649–654. DOI: 10.3233/JAD-2010-100225

[27] 9.Arrieta-Cruz I, Wang J, Pavlides C, Pasinetti GM. 卡维地洛可恢复阿尔茨海默病小鼠模型的长期痴呆。J Alzheimers Dis. 2010;21(2):649-654. doi:10.3233/JAD-2010-100225

[28] Wang J, Ono K, Dickstein DL, et al. Carvedilol as a potential novel agent for the treatment of Alzheimer’s disease. Neurobiol Aging. 2011;32(12):2321.e1–12. DOI: 10.1016/j.neurobiolaging.2010.05.004

[29] Wang J., Ono K., Dickstein D.L. et al. Carvedilol as a potential novel agent for the treatment of Alzheimer’s disease // Neurobiol. Aging. 2011. Vol. 32, No. 12. P. 2321.e1–12. DOI: 10.1016/j.neurobiolaging.2010.05.004

[30] 10.Wang J, Ono K, Dickstein DL, et al. 卡维地洛作为治疗阿尔茨海默病的潜在新药。Neurobiol Aging. 2011;32(12):2321.e1-2321.e23212. doi:10.1016/j.neurobiolaging.2010.05.004

[31] Beaman EE, Bonde AN, Ulv Larsen SM, et al. Blood-brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension. Brain. 2022;awac076. DOI: 10.1093/brain/awac076

[32] Beaman E.E., Bonde A.N., Ulv Larsen S.M. et al. Blood-brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension // Brain. 2022. P. awac076. DOI: 10.1093/brain/awac076

[33] 11. Beaman EE, Bonde AN, Ulv Larsen SM, et al. 血脑屏障渗透性β-受体阻滞剂与高血压患者的阿尔茨海默病风险降低有关[在线发表，2022年2月23日]。Brain. 2022;awac076. doi:10.1093/brain/awac076

[34] Nevado-Holgado AJ, Kim CH, Winchester L, et al. Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank. BMJ Open. 2016;6(11):e012177. DOI: 10.1136/bmjopen-2016-012177

[35] Nevado-Holgado A.J., Kim C.H., Winchester L. et al. Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank // BMJ Open. 2016. Vol. 6, No. 11. P. e012177. DOI: 10.1136/bmjopen-2016-012177

[36] 12.12.Nevado-Holgado AJ, Kim CH, Winchester L, Gallacher J, Lovestone S. 常见处方药与认知功能的关系：英国生物银行的一项横断面研究。BMJ Open. 2016;6(11):e012177. 2016年11月30日发表。DOI:10.1136/bmjopen-2016-012177。

[37] Burkauskas J, Noreikaite A, Bunevicius A, et al. Beta-1-selective Beta-blockers and cognitive functions in patients with coronary artery disease: a cross-sectional study. J Neuropsychiatry Clin Neurosci. 2016;28(2):143–146. DOI: 10.1176/appi.neuropsych.15040088

[38] Burkauskas J., Noreikaite A., Bunevicius A. et al. Beta-1-selective Beta-blockers and cognitive functions in patients with coronary artery disease: a cross-sectional study // J. Neuropsychiatry Clin. Neurosci. 2016. Vol. 28, No. 2. P. 143–146. DOI: 10.1176/appi.neuropsych.15040088

[39] 13. Burkauskas J, Noreikaite A, Bunevicius A, et al. β-1-选择性β-阻断剂与冠状动脉疾病患者的认知功能。一个横断面的研究。J Neuropsychiatry Clin Neurosci. 2016;28(2):143-146. doi:10.1176/appi.neuropsych.15040088

[40] Holm H, Ricci F, Di Martino G, et al. Beta-blocker therapy and risk of vascular dementia: a population-based prospective study. Vascul Pharmacol. 2020;125–126:106649. DOI: 10.1016/j.vph.2020.106649

[41] Holm H., Ricci F., Di Martino G. et al. Beta-blocker therapy and risk of vascular dementia: A population-based prospective study // Vascul. Pharmacol. 2020. Vol. 125–126. P. 106649. DOI: 10.1016/j.vph.2020.106649

[42] 14.Holm H, Ricci F, Di Martino G, et al. β-阻断剂治疗和血管性痴呆的风险。一项基于人群的前瞻性研究。Vascul Pharmacol. 2020;125-126:106649. doi:10.1016/j.vph.2020.106649

[43] Lobzin VYu, Emelin AYu. Depression and dementia: differentiation and comorbidity. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):100–106. (In Russ.). DOI: 10.14412/2074-2711-2020-4-100-106

[44] Лобзин В.Ю., Емелин А.Ю. Депрессия и деменция: дифференциация и коморбидность // Неврология, нейропсихиатрия, психосоматика. 2020. Т. 12, № 4. С. 100–106. DOI: 10.14412/2074-2711-2020-4-100-106

[45] 15.Lobzin V. Yu, Emelin A. Yu. 抑郁症和痴呆症：区别和合并症 // 神经学、神经精神病学和精神医学。- 2020. - Т. 12. - №. 4

[46] Kessing LV, Rytgaard HC, Ekstrøm CT, et al. Antihypertensive drugs and risk of depression: a nationwide population-based study. Hypertension. 2020;76(4):1263–1279. DOI: 10.1161/HYPERTENSIONAHA.120.15605

[47] Kessing L.V., Rytgaard H.C., Ekstrøm C.T. et al. Antihypertensive drugs and risk of depression: a nationwide population-based study // Hypertension. 2020. Vol. 76, No. 4. P. 1263–1279. DOI: 10.1161/HYPERTENSIONAHA.120.15605

[48] 16.Kessing LV, Rytgaard HC, Ekstrøm CT, Torp-Pedersen C, Berk M, Gerds TA. 抗高血压药物和抑郁症的风险。一项全国性的基于人口的研究。Hypertension. 2020;76(4):1263-1279. doi:10.1161/HYPERTENSIONAHA.120.15605

[49] Vorobyeva OV, Pilipovich AA, Fateeva VV. Impact of endothelial inflammation on depression in patients with cerebral microangiopathy: a prospective study. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(1):32–37. (In Russ.). DOI: 10.14412/2074-2711-2022-1-32-37

[50] Воробьева О.В., Пилипович А.А., Фатеева В.В. Влияние эндотелиального воспаления на депрессию у пациентов с церебральной микроангиопатией: проспективное исследование // Неврология, нейропсихиатрия, психосоматика. 2022. Т. 14, № 1. С. 32–37. DOI: 10.14412/2074-2711-2022-1-32-37

[51] 17.Vorobyeva O. V., Pilipovich AA, FATEEVA V. V. 内皮炎症对脑微血管病患者抑郁症的影响：一项前瞻性研究。- 2022.

[52] Silva IVG, de Figueiredo RC, Rios DRA. Effect of different classes of antihypertensive drugs on endothelial function and inflammation. Int J Mol Sci. 2019;20(14):3458. DOI: 10.3390/ijms20143458

[53] Silva I.V.G., de Figueiredo R.C., Rios D.R.A. Effect of different classes of antihypertensive drugs on endothelial function and inflammation // Int. J. Mol. Sci. 2019. Vol. 20, No. 14. P. 3458. DOI: 10.3390/ijms20143458

[54] 18.Silva IVG, de Figueiredo RC, Rios DRA. 不同类别的抗高血压药物对内皮功能和炎症的影响。Int J Mol Sci. 2019; 20(14):3458. 2019年7月14日发表。DOI:10.3390/IJMS20143458

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Bogdanova T.A., Turusheva A.V.