Q&A from April 14, 2026 R3 Seminar

Dr. Frontera: I want to clarify that I wouldn’t say dementia is prevalent in our findings. What we mostly identified was mild cognitive impairment, which is a very specific diagnosis. One patient in our cohort developed dementia—an individual who worked in finance pre-COVID, had COVID, then experienced a significant decline and could no longer work. Generally, those with mild cognitive impairment were younger than we typically see in a non-COVID population. However, we primarily looked at individuals in their 50s and 60s, with a few cases in their 20s and 30s.

Dr. Becker: I agree with Dr. Frontera. The recent literature shows that older adults have a higher absolute dementia rate due to starting from a more vulnerable baseline, whereas younger patients exhibit an elevated relative risk after SARS-CoV-2 compared with older patients. 

Younger people with Long COVID do not show the same rates of dementia as older adults, and they show a different phenotype: one that is predominantly frontal-subcortical, characterized by processing speed and attention deficits rather than the memory-predominant, hippocampal pattern of dementias like Alzheimer’s. But the neurobiological injury is significant, measurable, and, in some biomarker studies, suggests accelerated brain aging. Whether this translates into earlier-onset neurodegenerative disease over the next decade is what longitudinal studies like RECOVER are built to determine, and it is one of the most pressing unanswered questions in the field.

Mr. Zissis: To insert an anecdotal perspective, I was 57 years old when my COVID symptoms began. While assessing cognitive symptoms, I often wonder what’s considered “normal” and how these neurocognitive issues affect younger patients. So, I’ve seen younger individuals with significant cognitive impacts, too.

Dr. Becker: When discussing variants, I prefer using variant “eras” because we cannot accurately identify the specific variant that infected an individual. Brain fog may be more prevalent in Long COVID cases stemming from the Omicron era, even though the overall prevalence of Long COVID has decreased. Earlier variants were associated with symptoms like shortness of breath and anosmia, whereas Omicron seemed more linked to brain fog and fatigue, although geographic variation complicates these findings.

Dr. Frontera: No. We did not find differences in ventricular size in our cohort. For an increase in ventricular size to occur, significant atrophy would need to be present, which typically points toward dementia. In our study, we did not find differences in ventricular volume. Our patients are getting serial magnetic resonance imaging (MRI) scans, and we’re currently analyzing changes over time.

Dr. Becker: There’s no single test that differentiates them cleanly. There’s substantial symptom overlap, especially because women aged 45 to 54 are disproportionately affected by Long COVID. However, we observe cognitive patterns in Long COVID that differ from typical patterns seen in menopause. During neuropsychological assessments, we look at the nature and degree of deficits relative to someone’s baseline and established profiles for menopause.

Dr. Becker: Dr. Nath showed that in severe COVID, there can be a loss of neurons in brain stem regions that control automatic breathing, likely from inflammation and vascular injury. In Long COVID, we usually don’t see that level of structural damage, but the same brain stem–autonomic systems may be dysregulated. RECOVER Cycle 1 did use MRI scans, but we will not be repeating them as part of the standard protocol in Cycle 2.

Dr. VanElzakker: Yes. I think that’s exactly right. There’s the damage in the acute phase, then there are lingering inflammatory responses. A big area of inflammatory communication between the peripheral body and the brain is the brain stem. It’s where, for example, the vagus nerve, which detects inflammation in the body, sends a signal to the brain that says, “Your body is sick, go to bed, you feel sick right now,” which also triggers an inflammatory response. The cluster where the vagus nerve enters the brain stem is surrounded by autonomic nuclei, including nuclei that are important in breathing. It’s probably, for most Long COVID patients, not going to manifest like, “I have to remember to keep breathing or I’ll forget,” but we think that maybe that’s part of why, for example, they may have lost some control over heart rate, when normally they could go from lying down to standing up. Normally, we all make these very subtle but important adjustments so that we don’t pass out when the blood rushes to our feet, and that sort of thing can be disrupted because the inflammatory process adds some signal-to-noise disruption. 

Dr. Frontera: I can also add that we are looking at MRI data. Cycle 1 has a large segment on MRI. Much of the post-processing of the data has been completed, and we’re moving into analysis stages. Multiple other National Institutes of Health–funded studies outside of RECOVER are also looking at neuroimaging. So there’s a lot more information to come.

Dr. Becker: Your brain stem is basically your autopilot for breathing. COVID can damage the neurons in that autopilot center, which means during sleep, when you’re not consciously thinking about breathing, the signal can fail or weaken. This is different from typical sleep apnea. Some Long COVID patients describe having to consciously remind themselves to breathe, which explains why standard treatments like continuous positive airway pressure (CPAP) may not fully fix the problem.

Dr. Becker: Language disturbances are most commonly word-finding difficulty. But these are typically influenced by things like executive functioning and processing speed. In my presentation, I mentioned that cognitive domains don’t work in isolation. This is the perfect example where executive functioning and processing speed deficits can cascade into slowed semantic access, which is the retrieving of words from our semantic “bank,” so to speak. Phonemic paraphasia is when people are making specific errors when they’re saying words. This can happen especially under cognitive load or fatigue. We find that verbal fluency impairment is often related to initiation of speech, which, again, has prefrontal executive demands. 

Also, some people will say that they have difficulty putting a sentence together, and that is really challenging, which I attribute in part to reduced working memory. This is meaningful in that it’s different from what we see in a primary language disorder. It resembles frontotemporal disruptions, and maybe even disruptions in white matter pathways, which is different from the typical temporal profile that we see with patients with primary language disorders. I think more granular language assessments are needed, but these are on our radar and certainly included for Cycle 2.

Dr. Becker: Cognitive assessments act as neuroanatomical fingerprints: the specific pattern of deficits maps to frontal-subcortical circuits that are also responsible for autonomic regulation, olfactory processing, and sleep-wake architecture, meaning cognitive data help localize where any damage might be. Anosmia, for example, has been shown to specifically predict memory impairment. So when cognitive profiles co-occur systematically with dysautonomia, sleep apnea, or anosmia across thousands of RECOVER participants, we can identify shared biological mechanisms that may be driving these symptoms simultaneously.

Dr. VanElzakker: This PolyBio-funded study will study Maraviroc and Truvada.

Dr. Becker: Sleep problems are included as part of our surveys but not framed as a neurodegenerative damage outcome per se. They would probably sit primarily in the cardiopulmonary and infection-associated chronic condition domains. Sleep disturbance and snoring/sleep apnea are included as Long COVID case definition symptoms and will be tracked longitudinally via survey.

Dr. Becker: Headache, including NDPH, is classified as a neurological symptom but sits in a separate domain from neurocognitive dysfunction. Yes—there is meaningful evidence for this, though much of it is mechanistic and case-series level rather than large prospective cohort data.

Dr. Becker: The timeline is actually not as alarming as it sounds; the dementia risk studies are detecting early neurobiological signals over 2 to 5 years that represent the leading edge of a much longer causal arc, with the broader infection–dementia literature showing that elevated dementia risk from serious infections persists across follow-up periods of 25 to 30 years. Notably though, younger patients actually show a greater relative risk of neurodegeneration after SARS-CoV-2 than older patients (this was from a recent Lancet study), but older adults had a higher absolute dementia rate because they start from a more vulnerable baseline.

Dr. Becker: No single treatment has been proven definitively effective for Long COVID brain fog yet, but the most evidence-supported treatments currently are managing underlying contributors, like treating sleep disorders, addressing orthostatic intolerance/postural orthostatic tachycardia syndrome, optimizing cardiovascular health, and pacing activity to avoid post-exertional crashes. Regarding dissemination, research findings are usually published and presented at society conferences, but the honest reality is that the pipeline from research to PCP/neurology practice lags a bit behind the science.

Dr. Becker: Yes. Per Abramoff et al., prior TBI is increasingly recognized as a vulnerability factor that can amplify Long COVID cognitive impairment, because both conditions share overlapping mechanisms of neuroinflammation, white matter disruption, and reduced cognitive reserve.

Dr. Becker: Yes! RECOVER and several Long COVID research programs collect sleep measures alongside cognitive assessments specifically to examine how sleep disruption contributes to and predicts cognitive impairment trajectories.

Dr. Frontera: Yes. Thank you! SCD is very common as well. In fact, most people who notice brain fog test abnormal on SCD metrics (Cognitive Change Index and other inventories). SCD is a risk factor for the development of dementia, but less so than for an MCI–Alzheimer’s disease diagnosis.

RECOVER Admin: Here are a few key references in the presentations: 

• Dr. Becker’s study about olfactory dysfunction after SARS-CoV-2 infection
• Dr. VanElzakker’s study about neuroinflammation in Long COVID patients 
• Dr. Frontera’s study about MCI in Long COVID patients 
• Dr. Frontera’s study about brain tissue alterations in Long COVID and their associations with Alzheimer’s risk
• Results from the RECOVER-NEURO clinical trial

RECOVER Admin: Some adults from the first phase of RECOVER’s observational study will be invited to continue into the second phase. If you are invited, your study team will contact you by phone or email with details about what to expect. Talking with your study team does not mean you have to participate.

RECOVER Admin: Please see the RECOVER website for more information on how to become a RECOVER Representative.

You can get involved with RECOVER even if you’re not enrolled in a study or serving as a Representative:

• Share recoverCOVID.org with your family, friends, and neighbors who want to know more about Long COVID or RECOVER.
• Sign up for email updates.
• Attend R3 Seminars.
• Track RECOVER’s impact.
• Spread the word about RECOVER on social media.
• Contact RECOVER.

Check the RECOVER website regularly for new opportunities to learn about, support, and contribute to RECOVER’s Long COVID research.

Dr. Becker: EEG has a lot of potential and can sometimes detect subtle changes in how brain networks are communicating or processing information. That said, EEG is not a definitive diagnostic test for most conditions involving cognition because findings are often nonspecific, meaning similar patterns can occur for different reasons, like fatigue, poor sleep, pain, neurologic conditions, and so on. A normal EEG also does not rule out real cognitive difficulties. EEG can be considered a small piece of the puzzle, but it is not a standalone answer. 

Dr. Becker: A consistently elevated heart rate can contribute to cognitive impairment and post-exertional malaise by increasing physiologic stress and impairing the body’s ability to regulate blood flow to the brain, particularly during activity or upright posture. This can lead to symptoms such as brain fog, mental fatigue, dizziness, and worsening symptoms after physical or cognitive exertion.

Dr. Becker: Many patients experience meaningful cognitive decline relative to their own premorbid baseline despite scoring within broad normative limits on standardized tests. So, an approach that analyzes individualized discrepancy scores (e.g., comparing current performance with estimated premorbid ability) is often preferred. This is particularly important in high-functioning individuals, where a substantial decline in efficiency or functional capacity may still fall above conventional impairment cutoffs.

Dr. Becker: White matter hyperintensities may reflect subtle injury or dysfunction in the brain’s connective networks, potentially related to inflammation, immune activation, small vessel changes, or disruption of the blood–brain barrier. Because efficient cognition depends on communication across distributed brain networks, even relatively nonspecific white matter abnormalities may contribute to symptoms such as slowed processing speed, reduced attention, mental fatigue, and “brain fog.” Importantly, these MRI findings are often nonspecific and do not always correlate directly with symptom severity, suggesting that brain fog likely reflects a combination of structural, physiologic, and network-level dysfunction.

Dr. Becker: Yes. Difficulties processing visual information can be considered part of cognitive dysfunction or “brain fog,” particularly when they involve slowed interpretation, impaired visual attention, difficulty tracking complex visual environments, or increased mental fatigue from visual tasks. These symptoms may reflect dysfunction in attention, processing speed, visuospatial processing, or broader brain network efficiency rather than a primary problem with eyesight itself. Patients often describe this as feeling visually overwhelmed, mentally slowed, or unable to efficiently process what they are seeing.