Long COVID and the Brain: Links to Alzheimer’s-Related Changes

Date Submitted: 9/3/2025

Date Accepted: 9/14/2025

COVID-19 was once thought of as a lung disease, but we now know it can affect many parts of the body, extending beyond the lungs. Between 20% and 60% of people who recover from COVID-19 have long-lasting symptoms more than 12 weeks after infection (1,2). This condition is called post-acute sequelae of SARS-CoV-2 (PASC), also known as “long COVID” (1,2,3,4). The symptoms of long COVID include dysfunction of the brain and nervous system, causing what many describe as “brain fog”, a cognitive impairment characterized by sleep disturbance, slowed thinking, problems with concentration, executive function, memory, attention and processing speed (5,6). Among these symptoms, poor concentration is the most common cognitive complaint and can limit daily life for up to a year after infection. Scientists have also found changes in the blood of people with long COVID that look similar to changes seen in Alzheimer’s disease (16). These include lower levels of a protein called Aβ42 compared to Aβ40, higher levels of another protein called phosphorylated tau-181, and increases in immune system signals called IL-6 and IFN-γ (8,15,18,19,20, Figure 1). Taken together, the story becomes clearer: the cognitive impairment of long COVID, blood markers that echo Alzheimer’s disease, and decades of research on how viruses affect the brain all point to the same possibility - that COVID-19 could drive long-term problems with memory and cognition.

Figure 1. Biomarkers in the blood and brain that are linked to long-term thinking and memory problems after COVID-19.

A paper titled “Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer’s Disease” reviewed the current research on the connection between COVID-19 and Alzheimer’s Disease (7). The authors looked for scientific papers with search terms that examined COVID-19 and its effects on memory and cognition, such as cognitive or neurocognitive impairment of COVID-19 / SARS-CoV-2 / long COVID and biomarkers of cognitive impairment and Alzheimer’s disease. To make sure their information was reliable, they focused mostly on large studies that combine results from many smaller ones. These types of studies give a clearer picture of how common COVID-related thinking problems really are (7).

Researchers are finding more and more signs that COVID-19 may have similar changes that are seen in Alzheimer’s disease. In both the blood and the brain, researchers see shifts in key proteins, amyloid and tau, that usually show up years before dementia begins. This matters because these proteins are early warning signs of brain aging and memory loss. One long-term study even found that a 2% drop in the amyloid ratio (Aβ42 : 40) in the blood was equal to about four years of extra brain aging (8). Patients who were older or hospitalized with COVID showed even bigger spikes in p-tau-181 (8), suggesting the virus may speed up harmful brain processes.

These Alzheimer’s-related key protein changes go hand in hand with other warning signs of brain damage. SARS-CoV-2 virus is thought to directly attack brain regions that are critical for memory, such as the entorhinal cortex, hippocampus, frontal lobe, and temporal lobe. These regions are often disrupted in Alzheimer’s disease and have shown signs of damage in people after COVID-19, helping explain the “brain fog” and memory problems many survivors report (Figure 2,3). The virus may even enter through the nose and travel along nerve pathways into the hippocampus, because neurons in that area carry ACE2 receptors, which are the same receptors the virus uses to invade the brain. On the other hand, ACE2 is already higher than normal in AD brains, which may make the brain even more vulnerable.

Figure 2. Brain regions most affected by COVID-19 and linked to memory and thinking. This diagram highlights four brain areas that play key roles in memory, attention, and decision-making.Incoming information passes through the entorhinal cortex (deep blue), which serves as a gateway to the hippocampus (teal). The hippocampus organizes and stores these experiences as long-term memories, with support from the temporal lobe (green), which helps with language and recognition. The frontal lobe (light blue) uses this stored information to focus attention, plan, and make decisions. Together, these regions form a memory-and-decision network.

Figure 3. How key brain regions process information, store memories, and guide decisions.

But the virus doesn’t just harm the brain by getting inside it. COVID-19 may also trigger persistent systemic inflammation in the body, with high levels of immune signals like pro-inflammatory markers IL-6 and other neurotoxic cytokines in the central nervous system (9, 10, 11). These biomarkers remain elevated for 8 months after infection and correlate with slower reaction times and weaker working memory. Severe infections add further stress through hypoxia (lack of oxygen), mechanical ventilation, or delirium from acute respiratory distress syndrome (ARDS) can injure white matter, raise stroke risk, and leave behind long-lasting thinking and memory problems.

On top of that, doctors find that the brains of people with severe COVID-19 show signs of injury, similar to or even worse than those seen in Alzheimer’s disease without COVID (12). Blood tests reveal damage to neurons and their support cells and one marker called neurofilament light chain (NFL) stays high for at least three months after infection (17, Figure 1). Other markers, like VEGF, are correlated with attention deficits remain elevated, showing that blood vessel injury in the brain may also play a role (13, Figure1). This matters because many people with conditions such as diabetes, high blood pressure and vascular injury are even more vulnerable, as their brains are generally less able to handle stress, and COVID-19 seems to make this worse. Large studies confirm the risk: people who had COVID are more likely to later develop dementia or Parkinson’s disease, and many continue to struggle with fatigue, brain fog, memory loss, or trouble paying attention months later (14). Overall, the evidence shows that COVID-19 does not just cause short-term sickness, but can also trigger long-tasting brain and memory problems, especially in people already at risk and being vulnerable. Recognizing this connection is important, because it highlights who may need extra monitoring and care after infection.

COVID-19 can set off changes in the brain that look like Alzheimer’s and damage blood vessels in the brain, keeping the immune system in the brain on high alert. These combined problems weaken important brain networks and help explain why many people experience lasting memory and thinking difficulties after infection. What we don’t yet know is whether COVID-19 starts a brand-new kind of brain disease, or if it speeds up conditions like Alzheimer’s that may already be quietly developing. To get clear answers, researchers need to follow people over time, starting before infection and tracking them with brain scans and blood tests. They also need to compare differences by virus strain and vaccination status. Understanding whether COVID-19 creates new damage or accelerates existing brain disease will shape how we treat patients, how we monitor survivors, and how we prepare for long-term effects of the pandemic.

This paper covers a lot of ideas that are not discussed here, but one important point is that COVID-19’s impact on the brain is not rare. In fact, neurological problems are the most common effects of the virus outside the lungs. Thinking and memory issues have been found in people across the whole range of illness, from those with only mild symptoms to patients in the Intensive Care Unit (aka ICU, the part of a hospital where the sickest patients go) who needed oxygen or a ventilator. 

The chances of developing lasting cognitive problems are much higher for people who are older, already have weaker memory systems, live with health conditions like diabetes or high blood pressures, or went through ICU complications like delirium or ARDS. Because these risk factors overlap, sometimes it is hard to tell what damage comes directly from the virus and what comes from the pre-existing health problems. 

That’s why doctors need to pay close attention to brain health in COVID survivors, especially those with risk factors for dementia or those who were very sick. Simply performing memory tests and cognitive screening regularly and adjusting the frequency to each patient’s needs are a good starting point. On a larger scale, public health leaders should plan for the long-term impact of “long COVID” on the brain, since problems with memory, attention, and decision-making not only affect individuals, but also reduce workforce productivity, weaken social participation, and lower quality of life, especially in countries with most aging populations like Japan, Italy and Germany.

Catching memory and thinking problems early is key. It gives doctors time to start rehab programs, teach caregivers how to help, and set up workplace support before daily skills are permanently lost. Long-term checkups should include all COVID survivors, even those who never complained of brain fog, because early brain changes can happen silently. Regular memory tests, along with simple blood tests for proteins linked to Alzheimer’s disease, could potentially spot problems years before dementia fully develops.

It’s also important to track heart and blood vessel health, since problems like high blood pressure and stroke are closely tied to both COVID-19 and dementia. Looking ahead, post-pandemic care should be broad: it should combine brain rehab, heart and vessel care, and social support programs. Doing so can help reduce the long-term burden of COVID-related memory and thinking problems.

About the Author:

Amy (Hoi Kei) Choi: hoikei@umich.edu, University of Michigan

References: 

1. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22. PMID: 33753937; PMCID: PMC8893149.

2. Dixit NM, Churchill A, Nsair A, Hsu JJ. Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known? Am Heart J Plus. 2021 May;5:100025. doi: 10.1016/j.ahjo.2021.100025. Epub 2021 Jun 24. PMID: 34192289; PMCID: PMC8223036.

3. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nat Med. 2020 Jul;26(7):1017-1032. doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10. PMID: 32651579; PMCID: PMC11972613.

4. Mehandru S, Merad M. Pathological sequelae of long-haul COVID. Nat Immunol. 2022 Feb;23(2):194-202. doi: 10.1038/s41590-021-01104-y. Epub 2022 Feb 1. PMID: 35105985; PMCID: PMC9127978.

5. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M, Meziani F. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Jun 4;382(23):2268-2270. doi: 10.1056/NEJMc2008597. Epub 2020 Apr 15. PMID: 32294339; PMCID: PMC7179967.

6. Crivelli L, Palmer K, Calandri I, Guekht A, Beghi E, Carroll W, Frontera J, García-Azorín D, Westenberg E, Winkler AS, Mangialasche F, Allegri RF, Kivipelto M. Changes in cognitive functioning after COVID-19: A systematic review and meta-analysis. Alzheimers Dement. 2022 May;18(5):1047-1066. doi: 10.1002/alz.12644. Epub 2022 Mar 17. PMID: 35297561; PMCID: PMC9073922.

7. Doskas T, Vavougios GD, Kormas C, Kokkotis C, Tsiptsios D, Spiliopoulos KC, Tsiakiri A, Christidi F, Aravidou T, Dekavallas L, Kazis D, Dardiotis E, Vadikolias K. Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer's Disease. Brain Sci. 2025 May 25;15(6):564. doi: 10.3390/brainsci15060564. PMID: 40563736; PMCID: PMC12191038.

8. Duff EP, Zetterberg H, Heslegrave A, Dehghan A, Elliott P, Allen N, Runz H, Laban R, Veleva E, Whelan CD, Sun BB, Matthews PM. Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection. Nat Med. 2025 Mar;31(3):797-806. doi: 10.1038/s41591-024-03426-4. Epub 2025 Jan 30. PMID: 39885359; PMCID: PMC11922756.

9. Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, Adams G, Hornick JL, Padera RF Jr, Sabeti P. Neuropathological Features of Covid-19. N Engl J Med. 2020 Sep 3;383(10):989-992. doi: 10.1056/NEJMc2019373. Epub 2020 Jun 12. PMID: 32530583; PMCID: PMC7304421.

10. Breton G, Mendoza P, Hägglöf T, Oliveira TY, Schaefer-Babajew D, Gaebler C, Turroja M, Hurley A, Caskey M, Nussenzweig MC. Persistent cellular immunity to SARS-CoV-2 infection. J Exp Med. 2021 Apr 5;218(4):e20202515. doi: 10.1084/jem.20202515. PMID: 33533915; PMCID: PMC7845919.

11. Kang CK, Kim M, Lee S, Kim G, Choe PG, Park WB, Kim NJ, Lee CH, Kim IS, Jung K, Lee DS, Shin HM, Kim HR, Oh MD. Corrigendum to: Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Infect Dis. 2023 Apr 26;227(9):1113-1114. doi: 10.1093/infdis/jiab557. Erratum for: J Infect Dis. 2021 Jul 2;224(1):39-48. doi: 10.1093/infdis/jiab159. PMID: 35258550; PMCID: PMC9383586.

12. Frontera JA, Boutajangout A, Masurkar AV, Betensky RA, Ge Y, Vedvyas A, Debure L, Moreira A, Lewis A, Huang J, Thawani S, Balcer L, Galetta S, Wisniewski T. Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia. Alzheimers Dement. 2022 May;18(5):899-910. doi: 10.1002/alz.12556. Epub 2022 Jan 13. PMID: 35023610; PMCID: PMC9011610.

13. Serrano-Castro PJ, Garzón-Maldonado FJ, Casado-Naranjo I, Ollero-Ortiz A, Mínguez-Castellanos A, Iglesias-Espinosa M, Baena-Palomino P, Sánchez-Sanchez V, Sánchez-Pérez RM, Rubi-Callejon J, Estévez-María JC, Galeano-Bilbao B, Romero-Imbroda J, Sobrino B, Arrabal-Gomez C, Oliver-Martos B, Muñoz-Becerra L, Requena N, González Álvarez de Sotomayor MDM, Estivill-Torrus G, Suarez J, Ciano-Petersen NL, Pons-Pons G, Reyes-Bueno JA, Cabezudo-Garcia P, Aguilar-Castillo MJ, De la Cruz Cosme C, Duque-Holguera M, Cuartero-Rodriguez E, Vilches-Carrillo RM, Carrera-Muñoz I, Carnero-Pardo C, Ramirez-Garcia T, Oropesa JM, Dominguez-Mayoral A, Pelaez-Viñas N, Valiente L, de Fonseca FR. The cognitive and psychiatric subacute impairment in severe Covid-19. Sci Rep. 2022 Mar 3;12(1):3563. doi: 10.1038/s41598-022-07559-9. PMID: 35241761; PMCID: PMC8894467.

14. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021 May;8(5):416-427. doi: 10.1016/S2215-0366(21)00084-5. Epub 2021 Apr 6. PMID: 33836148; PMCID: PMC8023694.

15. Tavares-Júnior JWL, de Souza ACC, Borges JWP, Oliveira DN, Siqueira-Neto JI, Sobreira-Neto MA, Braga-Neto P. COVID-19 associated cognitive impairment: A systematic review. Cortex. 2022 Jul;152:77-97. doi: 10.1016/j.cortex.2022.04.006. Epub 2022 Apr 18. PMID: 35537236; PMCID: PMC9014565.

16. Wang H, Lu J, Zhao X, Qin R, Song K, Xu Y, Zhang J, Chen Y. Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures. Neurol Sci. 2021 Dec;42(12):4913-4920. doi: 10.1007/s10072-021-05616-1. Epub 2021 Sep 22. Erratum in: Neurol Sci. 2021 Dec;42(12):5443. doi: 10.1007/s10072-021-05680-7. PMID: 34550494; PMCID: PMC8455804.

17. Huang Z, Haile K, Gedefaw L, Lau BW, Jin L, Yip SP, Huang CL. Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis. Int J Mol Sci. 2023 Oct 30;24(21):15738. doi: 10.3390/ijms242115738. PMID: 37958721; PMCID: PMC10649265.

18. Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, Juno JA, Burrell LM, Kent SJ, Dore GJ, Kelleher AD, Matthews GV. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022 Feb;23(2):210-216. doi: 10.1038/s41590-021-01113-x. Epub 2022 Jan 13. PMID: 35027728.

19. Baiardi S, Quadalti C, Mammana A, Dellavalle S, Zenesini C, Sambati L, Pantieri R, Polischi B, Romano L, Suffritti M, Bentivenga GM, Randi V, Stanzani-Maserati M, Capellari S, Parchi P. Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias. Alzheimers Res Ther. 2022 Oct 12;14(1):153. doi: 10.1186/s13195-022-01093-6. PMID: 36221099; PMCID: PMC9555092.

20. Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29. PMID: 34973396; PMCID: PMC8715665.