NeuroVoices: Jacqueline Becker, PhD, on Brain Fog, Alzheimer Risk, and Treatment Advances in Long COVID

Long COVID continues to affect a substantial share of patients following SARS-CoV-2 infection, with cognitive symptoms, commonly described by patients as brain fog, among its most persistent and functionally disabling features. In a prior study published in the Journal of Rehabilitation Medicine, cognitive deficits in attention, processing speed, and working memory remained present in most patients assessed 3 years after COVID-19 infection.¹ These findings point to the durability of neurocognitive impairment in Long COVID, even years removed from the initial infection.

As understanding of the biological drivers of Long COVID continues to evolve, dedicated post-COVID clinical and research programs have emerged to manage the condition's considerable heterogeneity. According to a previous study of patients at a dedicated post-COVID-19 clinic published in PLoS One, anxiety symptoms were the strongest correlate of overall symptom burden, a finding that supports whole-person, multidisciplinary care models rather than symptom-by-symptom management alone.² Academic medical centers, including the Mount Sinai Long COVID program and its affiliated neuropsychology program, have built out specialized pathways to address these gaps.

Jacqueline Becker, PhD, a clinical neuropsychologist and assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, has studied the neurocognitive effects of SARS-CoV-2 since 2020. Her group recently contributed to a cohort study published in JAMA Network Open showing that objectively measured olfactory dysfunction was common after SARS-CoV-2 infection and was associated with a higher rate of self-reported cognitive problem.³ In a new iteration of NeuroVoices, Becker discussed why brain fog persists in some patients with Long COVID and resolves in others, what current data suggest about a link to Alzheimer disease (AD), and which treatments and referral considerations are most relevant for clinicians today.

NeurologyLive: Why do some patients with Long COVID get brain fog that sticks around, while others recover quickly?

Jacqueline Becker, PhD: We like to think of cognitive symptoms as being like the tip of the iceberg with Long COVID. So, what lies underneath that iceberg is all of the different mechanisms that may cause it like neuroinflammation, mitochondrial function, potentially an aberrant autoimmune response. There's also some evidence to suggest microbiome dysfunction or autonomic dysfunction may cause Long COVID as well.

There are many reasons that patients with Long COVID might have brain fog, but it's likely different in everybody. Why some patients might recover from brain fog is also very different. It's possible that some patients experience resolution of, for example, the neuroinflammation, and it's possible that there are some pharmaceuticals that we are now seeing show promise. For example, low-dose naltrexone and GLP-1s have shown some promise off-label in helping patients who have brain fog from Long COVID. But really, we don't have an answer yet as to why some people may have it and others don't, and why some people recover and others don't.

Is there any evidence that Long COVID brain fog raises a patient’s risk of AD down the road?

There are a few signals that make us a little bit concerned about that. I want to say upfront that in no way am I claiming that Long COVID causes AD, or that we have any evidence right now that SARS-CoV-2 can cause AD. We don't have the data yet to make those claims but there are some preliminary converging signals that do warrant investigation.

For example, last year, we showed that there is a signal with olfactory dysfunction, which is basically a loss of sense of smell or taste. We showed that patients who report brain fog in Long COVID sometimes have olfactory dysfunction as well. Again, we don't have yet enough data on this, but considering the connection that one, olfactory dysfunction is a common and often persistent symptom in long COVID, and two, it has been recognized as an early marker of neurodegeneration in other populations, and often precedes cognitive decline by many years, we think that tracking this over time is of interest and something that researchers should be focusing on.

The second concern comes from blood-based biomarkers, where we have a lot of studies showing that phosphorylated tau, which is found in some neurodegenerative conditions, is elevated in patients with the neurologic symptoms of Long COVID compared both with uninfected controls and in infected individuals without neurologic symptoms. So, finding that it's elevated in people with Long COVID and brain fog or other neurologic symptoms does raise this question of whether SARS-CoV-2 is accelerating or unmasking a neurodegenerative process in vulnerable individuals. But right now, we have all of these signals in isolation.

The other thing that we do know is that there were many viruses in the past, such as human herpesviruses, and Epstein-Barr virus (EBV), have certain links to AD and other neurodegenerative conditions. EBV is now well recognized in multiple sclerosis, and so it's certainly conceivable that this would be the case for patients with SARS-CoV-2 infection. But, we don't know why this happens to some patients and not others. The idea is that there may be some genetic predisposition, and then getting the virus starts this cascade. All we have is these isolated signals and hypotheses at the moment, and we don't have all of these data linked together.

What treatments are showing the most promise for Long COVID cognitive symptoms right now?

There are many treatments that I think show promise but have not been clearly established yet. One of the most promising supportive approaches that are relatively benign is something called cognitive rehabilitation, which is essentially done by a neuropsychologist, sometimes a speech and language pathologist. It's based on the idea that the brain is plastic and that neurons that fire together wire together, and that we can improve certain cognitive domains. That said, it hasn't really panned out as well as we've hoped in Long COVID. But anecdotally and qualitatively, many patients do report a lot of improvement after cognitive rehabilitation.

We did just complete a pilot randomized clinical trial doing microtesla magnetic therapy, which is a novel device. We did the first-in-human study, and it showed potential benefits as well. Primarily we showed that it was safe in humans and again, qualitatively, a lot of people reported improvements in that. So that's another potential treatment for cognitive dysfunction in Long COVID. Then there are pharmaceuticals that are all based on anecdotal evidence at this point. But a lot of patients have said that low-dose naltrexone, sometimes if it's started at an exceptionally low dose and titrated up, because these patients tend to be very sensitive, that has been beneficial for fatigue specifically, which in turn helps the brain fog.

GLP-1s like tirzepatide and semaglutide have also been shown, again qualitatively, to be helpful for cognition. Patients sometimes will say that they felt better seemingly overnight.

So, it's unclear who benefits most from which treatment. I think that's been largely a big problem in the clinical trials that we've seen so far, and why we've had so many negative results from a lot of these clinical trials. I think it's that there's substantial heterogeneity, where a lot of these patients with Long COVID are all different. Both in terms of the underlying mechanisms causing their Long COVID and their cognitive dysfunction, as well as which treatments they'll benefit from based on what their specific individual factors are and their comorbidities.

I think one of the biggest issues we have in the field right now is that we tend to lump everybody into a Long COVID bucket, and then we do clinical trials. I think it mitigates and waters down a lot of these treatment effects, because there may be some patients in those buckets who are really benefiting from these treatments, but they're probably different than the nonresponders. I hope part of what will be the next wave of clinical trials is getting more at the different endotypes and phenotypes of Long COVID, so that we can better figure out what treatments will help which people.

What should clinicians know about brain fog and a dedicated program for patients with Long COVID?

I would want physicians to know that brain fog is a real and disabling symptom of Long COVID, and even when a routine neurologic exam or MRI is normal, it doesn't mean that there's nothing happening cognitively. I think that it is important to refer to a specialized neuropsychologist. I think that's where neuropsychology can be particularly helpful, considering referrals when cognitive symptoms are persistent and functionally significant, especially. Also, when there's a mismatch between what the patient is experiencing and what a physician sees on a brief cognitive screen, or when a physician really wants to understand what exactly is impaired, and how can we capitalize on a patient's strengths to compensate for some of their weaknesses.

Typically, in Long COVID, we'll see weaknesses in executive functioning, in sustained attention, and in processing speed. Sometimes we can use that information that we get from a neuropsychic evaluation and leverage the strengths that a patient may have. Maybe it's in memory, maybe it's in language, to really put support in place so that they're able to compensate for some of their cognitive weaknesses. A referral to us can also help when a someone is making determinations about returning to work or making workplace or school accommodations, as well as disability evaluations.

We're involved in a lot of different national research studies and clinical trials, and so we can find appropriate places for patients depending on their cognitive profiles. I think it's really important to just be mindful of when someone reports brain fog or cognitive dysfunction after COVID, to not dismiss it and to take what the patient's saying at face value.

Transcript edited for clarity. Click here to view more NeuroVoices.

REFERENCES
1. Björkdahl A, Larsson J. Neuropsychological consequences three years post-covid-19 are persistent and have great impact on everyday activities. J Rehabil Med. 2026;58:jrm45473. Published 2026 Aug 3. doi:10.2340/jrm.v58.45473
2. Brinkman N, Teunis T, Choi S, Ring D, Brode WM. Factors associated with the presence and intensity of ongoing symptoms in Long COVID. PLoS One. 2025;20(4):e0319874. Published 2025 Apr 23. doi:10.1371/journal.pone.0319874
3. Horwitz LI, Becker JH, Huang W, et al. Olfactory Dysfunction After SARS-CoV-2 Infection in the RECOVER Adult Cohort. JAMA Netw Open. 2025;8(9):e2533815. Published 2025 Sep 2. doi:10.1001/jamanetworkopen.2025.33815