Association between COVID-19 and mild neurocognitive disorder due to possible Alzheimer’s disease in pregeriatric adults
Resumen
Introduction: Signs of cognitive dysfunction have been reported in post-COVID syndrome. However, a significant association between COVID-19 and Alzheimer's disease, which shares many pathophysiological similarities, has not been established.
Objective: To evaluate the association between COVID-19 infection and the presence of mild neurocognitive disorder due to Alzheimer's disease in pre-geriatric adults.
Methods: An analytical observational study was conducted with 149 subjects with mild neurocognitive disorder due to possible Alzheimer's disease (cases) and 298 subjects with normal cognitive function (controls, 1:2 ratio) by simple random sampling. The crude odds ratio (OR) for COVID-19 were calculated using a contingency table, and the ORs by strata were determined with homogeneity test by the Breslow-Day method (p <
0.05), and the adjusted ORs were determined using the Mantel-Haenszel test with a 95 % confidence interval and significance level p < 0.05, to control for possible confounders.
Results: COVID-19 was associated with mild neurocognitive disorder due to possible Alzheimer's disease (OR = 8.57; 95 % CI: 5.34–13.72; p < 0.001). A consistent association was found among the different strata evaluated (OR: 4.821–12.173), and modification of the effect was ruled out with Breslow-Day tests, which showed significant heterogeneity between strata (p > 0.05). The association remained significant after adjustment for the different factors evaluated using the Mantel-Haenszel method (adjusted OR: 6.927–10.059).
Conclusions: SARS-CoV-2 infection may be a relevant risk factor for mild neurocognitive disorder due to Alzheimer's disease. Longitudinal studies with long-term follow-up are needed to elucidate the underlying mechanisms and confirm the association.
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1.Furman S, Green K, Lane TE. COVID-19 and the impact on Alzheimer's disease pathology. J Neurochem. 2024;168(10): 3415–29. DOI: 10.1111/jnc.15985
2.Sorkheh M, Weaver DF, Reed MA. COVID-19 as a Risk Factor for Alzheimer's Disease. J Alzheimers Dis. 2023;91(1):1-23. DOI: 10.3233/JAD-220800
3.Li W, Sun L, Yue L, Xiao S. Alzheimer's disease and COVID-19: Interactions, intrinsic linkages, and the role of immunoinflammatory responses in this process. Front Immunol. 2023; 14:1120495. DOI: 10.3389/fimmu.2023.11204
4.Doskas T, Vavougios GD, Kormas C, Kokkotis C, Tsiptsios D, Spiliopoulos KC, Tsiakiri A, Christidi F, Aravidou T, Dekavallas L, et al. Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer’s Disease. Brain Sciences. 2025; 15(6):564. DOI: 10.3390/brainsci15060564
5.Esquivel-Tamayo JA, Montoya-Pedrón A. Predictive model of mild neurocognitive disorder due to Alzheimer’s disease in Cuban adults. Revista Mexicana de Neurociencias. 2025; 26 (5). DOI: 10.24875/RMN.25000011
6.Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzzche PC, Vandenbroucke JP, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008; 61(4):344-9. DOI: 10.1016/j.jclinepi.2007.11.008
7.American Psychiatric Association. Washington, DC: American Psychiatric Association; © 2026 [citado 15/01/2026]. Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR); [aprox. 3 p.]. Disponible en: https://www.psychiatry.org/psychiatrists/practice/dsm
8.Broche Pérez Y, López Pujol HA. Validation of the Cuban Version of Addenbrooke's Cognitive Examination-Revised for Screening Mild Cognitive Impairment. Dement Geriatr Cogn Disord. 2017; 44(5-6):320-7. DOI:10.1159/000481345
9.Sousa L, Vivas L. Valores normativos del Addenbrooke’s Cognitive Examination (ACE) para población con bajo nivel socioeducativo[Resumen]. Neurol Arg. 2017; 9(4):219-224. DOI: 10.1016/j.neurarg.2017.07.005
10.Pan FF, Wang Y, Huang L, Huang Y, Guo QH. Validation of the Chinese version of Addenbrooke’s Cognitive Examination III for detecting mild cognitive impairment. Aging Ment Health. 2022; 26(2):384-91. https://oi.org/10.1080/13607863.2021.1881757
11.Cubaeduca. Portal Educativo Cubano. La Habana: CINESOFT; © 2026[actualización 06/2021; citado 15/01/2026]. El Sistema Nacional de Educación en Cuba; [aprox. 4 p.]. Disponible en: https://apirepo.cubaeduca.cu/v1/private/811fb4tgald/pedagogia2/co/modulo__7.html
12.CIUO. Clasificación Internacional Uniforme de Ocupaciones. [s.l]: Organización Internacional del Trabajo; © 1996-2017 [citado 15/1/2026]. Estructura de la CIUO-08 y concordancias previas con la CIUO-88; [aprox. 4 p.]. Disponible en: https://webapps.ilo.org/public/spanish/bureau/stat/isco/isco08/index.htm
13.World Medical Association. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Participants. JAMA. 2024; 23(18):e21972. DOI: 10.1001/jama.2024.2197
14.Thornberg UB, Andersson A, Lindh M, Hellgren L, Divanoglou A, Levi R. Neurocognitive deficits in COVID-19 patients five months after discharge from hospital. Neuropsychol Rehabil. 2023;33(10):1599–623. DOI: 10.1080/09602011.2022.2125020
15.Largent J, Xie Y, Knuth KB, Toovey S, Reynolds MW, Brinkley E, et al. Cognitive and other neuropsychiatric symptoms in COVID-19: analysis of person-generated longitudinal health data from a community-based registry. BMJ Open. 2023;13(6): e069118. DOI: 10.1136/bmjopen-2022-069118
16.Miskowiak KW, Pedersen JK, Gunnarsson DV, Roikjer TK, Podlekareva D, Hansen H, et al. Cognitive impairments among patients in a long-COVID clinic: prevalence, pattern and relation to illness severity, work function and quality of life. J Affect Disord. 2023;1(324):162–9. DOI: 10.1016/j.jad.2022.12.122
17.Peixoto VGMNP, Facci LA, Barbalho TCS, Souza RN, Duarte AM, Dos Santos MB, et al. Factors associated with older adults' cognitive decline 6 months after gamma-variant SARS-CoV-2 infection. Front Neurol. 2024;15:1334161. DOI: 10.3389/fneur.2024.1334161.
18.Shan D, Wang C, Crawford T, Holland C. Association between COVID-19 infection and new-onset dementia in older adults: a systematic review and meta-analysis. BMC Geriatr. 2024;24(1):940. DOI: 10.1186/s12877-024-05538-5.
19.Shrestha A, Chen R, Kunasekaran M, Honeyman D, Notaras A, Sutton B, et al. The risk of cognitive decline and dementia in older adults diagnosed with COVID-19: A systematic review and meta-analysis. Ageing Res Rev. 2024; 101:102448. DOI: 10.1016/j.arr.2024.102448.
20.Livingston G, Huntley J, Liu KY, Costafreda SG, Selbæk G, Alladi S, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024; 404(10452):572–628. DOI: 10.1016/S0140-6736(24)01296-0.
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Derechos de autor 2026 Julio Antonio Esquivel Tamayo, Arquímedes Montoya Pedrón
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