October 3, 2022

Medical Trend

Medical News and Medical Resources

The risk of Alzheimer’s disease increases by 50-80% within a year after COVID-19 infection

The risk of Alzheimer’s disease increases by 50-80% within a year after COVID-19 infection


New study: The risk of Alzheimer’s disease increases by 50-80% within a year after COVID-19 infection

According to the French “Echo” website, according to estimates released by the World Health Organization’s European Regional Office on the 13th, at least 17 million Europeans will suffer from the sequelae of the COVID-19 in 2020 and 2021.


Since the COVID-19 pandemic began in December 2019, more than 600 million people have been infected globally, resulting in more than 6 million deaths [1] .

In addition, some people infected with COVID-19 still have long-term sequelae even after they recover [2] , which has brought a heavy burden to the normal life of people around the world.


Although the core clinical manifestations of COVID-19 occur in the respiratory system, neurological manifestations are common in both acutely infected and recovered patients with COVID-19.

These neurological symptoms include decreased sense of smell and taste [3] , epilepsy [4] , cognitive decline [5] , delirium [6] and so on .

There is growing evidence that the coronavirus SARS-CoV-2 can invade the central nervous system and affect brain structure, metabolism, function and activity.

The Harvard University Stephen M. Smith team compared the brain MRI imaging findings of patients with COVID-19 infection before and after infection, and found that the gray matter of the orbitofrontal cortex and parahippocampal gyrus of the patients after infection was significantly thinned.

At the same time, the brain tissue after infection The overall volume showed significant shrinkage , and the related results were published in the journal Nature [7] .


Alzheimer’s disease, the most common form of dementia, currently affects 50 million people worldwide, and scientists estimate that this number will continue to increase in the coming decades [8] .

Brain atrophy and cognitive decline caused by COVID-19 are both core features of Alzheimer’s disease (AD) [9] , which quickly attracted the attention of scientists, whether COVID-19 has a certain relationship with the occurrence/development of AD.

What kind of connection? It is worth noting that we all know that ACE2 is a key receptor for coronavirus invading human cells, and in AD animal models, decreased angiotensin/ACE2 activity is associated with Tau hyperphosphorylation and increased amyloid beta (Aβ) pathology.

Regarding [10] , this has aroused our infinite reverie about the connection between COVID-19 and AD.


Recently, a research team from Case Western Reserve University published a retrospective study in the Journal of Alzheimer’s Disease [11] .

6,245,282 older adults (age ≥65 years) who visited between February 2021 and May 2021 found that patients with COVID-19 compared with non-COVID-19 patients were diagnosed with Alzheimer’s disease within 360 days of being diagnosed with COVID-19 .

The risk of Zheimer’s disease is significantly increased, especially in patients over the age of 85 and women who are at the greatest increased risk.


The risk of Alzheimer's disease increases by 50-80% within a year after COVID-19 infection


The researchers analyzed data from TriNetX electronic health records in the U.S., a database of more than 95 million inpatient and outpatient records from all 50 states across the U.S.

The study included 410,748 patients diagnosed with COVID-19 and 5,834,534 non-COVID-19 patients. Patients, compared with the Non-COVID cohort, the COVID cohort was older, had a higher proportion of Hispanics, had a lower proportion of unknown ethnicity, and had a higher proportion of comorbidities such as hypertension, diabetes, and overweight.

In order not to let these confounding factors affect the risk assessment of COVID-19 infection for newly diagnosed Alzheimer’s disease, the researchers performed propensity matching score (PSM) matching for factors such as age, gender, race, socioeconomic status, comorbidities , etc.

 There were no significant differences in the composition of the components of the matched cohorts.


The risk of Alzheimer's disease increases by 50-80% within a year after COVID-19 infection

Table 1: Differences in composition of COVID-19 and Non-COVID-19 cohorts before and after PSM matching


Next, the researchers grouped the cohort by age (65-74, 75-84, ≥85), race (black, white, Hispanic), and sex, and used a Cox proportional hazards model to find that no The COVID-19 cohort had a 69% increased risk of newly diagnosed Alzheimer’s disease compared to the COVID-19 cohort (HR: 1.69, 95% CI: 1.53-1.72), and this increased risk occurred by age, race, and gender in each group.


Among the age groups of the COVID-19 cohort, the ≥85-year-old group had the greatest increased risk of newly diagnosed Alzheimer’s disease, at 89%, while the 75-84-year-old group and the 65-74-year-old group had a 69% and 59% increased risk, respectively %.


Given that aging is a key risk factor for Alzheimer’s disease [12] , previous studies [13] have shown that the new coronavirus will induce cellular senescence-associated secretory phenotype (SASP) after infecting cells, that is, infected cells will secrete a variety of Inflammatory factors that cause cell senescence-like cycle arrest in nearby uninfected cells.

Does COVID-19 cause the aging of human cells through the systemic inflammation of SASP, thereby promoting the pathogenesis of Alzheimer’s disease?

This provides new ideas for us to uncover the molecular mechanism of Alzheimer’s disease.


In gender groupings, women with COVID-19 had an 82% increased risk compared with men (50%) .

In a variety of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, the prevalence of females is significantly higher than that of males, suggesting that female-specific factors such as sex chromosomes [14] and sex hormones play a role in the development of the disease.

Epidemiological surveys also show that the number of women with Alzheimer’s disease is twice as high as that of men.

Identifying the role and specific mechanism of gender as a variable in the pathogenesis of Alzheimer’s disease will be an important issue for our comprehensive understanding of Alzheimer’s disease.


Across ethnic groups, whether black, white, or Hispanic, the COVID-19 cohort showed an increased risk of Alzheimer’s disease (62%, 61%, and 25%, respectively), and due to the small sample size, Risk confidence intervals were wider for blacks and Hispanics than for whites.

In the United States, African-Americans have a much higher risk of developing Alzheimer’s disease than non-Hispanic whites, and studies have shown [15] that black Americans are more likely to develop Alzheimer’s disease due to their socioeconomic status (such as living environment) ) as in other ethnic groups, but is there a race-specific genetic predisposition to Alzheimer’s disease? This is for further research.

So far, no specific race has been found to be more susceptible to the new coronavirus. According to related studies [16] , ACE2, as a key receptor of SARS-Cov-2, has no obvious expression among races (Asian/Caucasian). 


The risk of Alzheimer's disease increases by 50-80% within a year after COVID-19 infection

Table 2: The risk of new-onset AD in the COVID-19 cohort in different age, gender, and ethnic groups was increased compared with the non-COVID-19 cohort


At present, our understanding of the molecular mechanisms of Alzheimer’s disease pathogenesis and the factors affecting the development of the disease are still limited.

Viral infection [17] and nervous system inflammation [18] are thought to be involved in the development of Alzheimer’s disease, and since SARS-CoV-2 infection is associated with abnormalities in the central nervous system, it has attracted great interest from scientists.

This retrospective cohort study from Case Western Reserve University found that the COVID-19 cohort can increase the risk of a new diagnosis of Alzheimer’s disease in the elderly (≥65 years old) within one year, providing us with an in-depth study of the occurrence of Alzheimer’s disease The molecular mechanism of development provides new ideas.

It also reminds us to continue to pay attention to patients who have been infected with COVID-19, and the sequelae of COVID-19 may bring longer-term physical and mental burdens to them and their families.








[2]Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2.Lancet. 2022;399(10343):2263-2264. doi:10.1016/S0140-6736(22)00941-2

[3] Púa Torrejón RC, Ordoño Saiz MV, González Alguacil E, et al. Smell and Taste Dysfunction in Pediatric Patients With SARS-CoV-2 Infection [published online ahead of print, 2022 Aug 1]. Pediatr Neurol. 2022;136:28-33. doi:10.1016/j.pediatrneurol.2022.07.006

[4]Saini L, Krishna D, Tiwari S, et al. Post-COVID-19 Immune-Mediated Neurological Complications in Children: An Ambispective Study [published online ahead of print, 2022 Jul 6].Pediatr Neurol. 2022;136:20-27. doi:10.1016/j.pediatrneurol.2022.06.010

[5]Singh Y, Singh SK, Dua K, Gupta G. A molecular study of aryl hydrocarbon receptor activation in COVID 19 associated cognitive impairment – Correspondence [published online ahead of print, 2022 Sep 9].Int J Surg. 2022;105:106895. doi:10.1016/j.ijsu.2022.106895

[6]Arnold C. Could COVID delirium bring on dementia?.Nature. 2020;588(7836):22-24. doi:10.1038/d41586-020-03360-8

[7]Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank.Nature. 2022;604(7907):697-707. doi:10.1038/s41586-022-04569-5

[8]Shi M, Li C, Tian X, Chu F, Zhu J. Can Control Infections Slow Down the Progression of Alzheimer’s Disease? Talking About the Role of Infections in Alzheimer’s Disease.Front Aging Neurosci. 2021;13:685863. Published 2021 Jul 22. doi:10.3389/fnagi.2021.685863

[9]Baranova A, Cao H, Zhang F. Causal effect of COVID-19 on Alzheimer’s disease: A Mendelian randomization study [published online ahead of print, 2022 Aug 30].J Med Virol. 2022;10.1002/jmv.28107. doi:10.1002/jmv.28107

[10]Kehoe PG, Wong S, Al Mulhim N, Palmer LE, Miners JS. Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology.Alzheimers Res Ther. 2016;8(1):50. Published 2016 Nov 25. doi:10.1186/s13195-016-0217-7

[11]Wang L, Davis PB, Volkow ND, Berger NA, Kaelber DC, Xu R. Association of COVID-19 with New-Onset Alzheimer’s Disease [published online ahead of print, 2022 Jul 29].J Alzheimers Dis. 2022;10.3233/JAD-220717. doi:10.3233/JAD-220717

[12]Guerrero A, De Strooper B, Arancibia-Cárcamo IL. Cellular senescence at the crossroads of inflammation and Alzheimer’s disease.Trends Neurosci. 2021;44(9):714-727. doi:10.1016/j.tins.2021.06.007

[13]Tsuji, S., Minami, S., Hashimoto, R.et al. SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response. Nat Aging 2, 115–124 (2022). https://doi.org/10.1038/s43587-022-00170-7

[14]Yu B, Qi Y, Li R, Shi Q, Satpathy AT, Chang HY. B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells.Cell. 2021;184(7):1790-1803.e17. doi:10.1016/j.cell.2021.02.015

[15]Younan D, Wang X, Gruenewald T, et al. Racial/Ethnic Disparities in Alzheimer’s Disease Risk: Role of Exposure to Ambient Fine Particles.J Gerontol A Biol Sci Med Sci. 2022;77(5):977-985. doi:10.1093/gerona/glab231

[16]DOI: 10.1101/2020.02.05.20020107

[17]Ge T, Yuan Y. Herpes Simplex Virus Infection Increases Beta-Amyloid Production and Induces the Development of Alzheimer’s Disease.Biomed Res Int. 2022;2022:8804925. Published 2022 Aug 31. doi:10.1155/2022/8804925

[18]Trares K, Bhardwaj M, Perna L, et al. Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study.Alzheimers Res Ther. 2022;14(1):128. Published 2022 Sep 9. doi:10.1186/s13195-022-01063-y

The risk of Alzheimer’s disease increases by 50-80% within a year after COVID-19 infection

(source:internet, reference only)

Disclaimer of medicaltrend.org