Structural brain changes in post-COVID condition and its relationship with cognitive impairment, 2024, Pacheco-Jaime et al.

Structural brain changes in post-COVID condition and its relationship with cognitive impairment
Pacheco-Jaime, Laura et 52 al.

It has been estimated that ~4% of individuals infected with SARS-CoV-2 will be diagnosed with post-COVID condition. Previous studies have evidenced the presence of cognitive dysfunction and structural brain changes in infected individuals; however, the relationship between structural changes and cognitive alterations in post-COVID condition is still not clear. Consequently, the aim of this work is to study structural brain alterations in post-COVID condition patients after almost 2 years of infection and their likely relationship with patients' cognitive impairment. Additionally, the association with blood biomarkers and clinical variables was also explored.

One hundred and twenty-eight individuals with post-COVID condition and 37 non-infected healthy controls from the Nautilus Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575) underwent structural brain magnetic resonance imaging and a comprehensive neuropsychological assessment. A subsample of 66 post-COVID participants also underwent blood extraction to obtain levels of blood biomarkers. Cortical thickness and subcortical volumes were obtained and analysed using FreeSurfer (v7.1). FMRIB Software Library software (v6.0.4) was used to perform grey matter voxel-based analysis and to study microstructural white matter integrity.

Patients with post-COVID performed significantly worse in working and verbal memory, processing speed, verbal fluency and executive functions, compared to healthy controls.

Moreover, patients with post-COVID showed increased cortical thickness in the right superior frontal and the right rostral middle frontal gyri that negatively correlated with working memory performance. Diffusion tensor imaging data showed lower fractional anisotropy in patients in the right superior longitudinal fasciculus, the splenium and genu of the corpus callosum, the right uncinate fasciculus and the forceps major, that negatively correlated with subjective memory failures.

No differences in blood biomarkers were found. Once patients were classified according to their cognitive status, post-COVID clinically cognitively altered presented increased cortical thickness compared to those classified as non-cognitively altered.

In conclusion, our study showed that grey and white matter brain changes are relevant in this condition after almost 2 years of infection and partly explain long-term cognitive sequelae. These findings underscore the critical importance of monitoring this at-risk population over time.

Link | PDF (Brain Communications) [Open Access]

 

You've answered but I was just about to say:

I'd have to check but my sense is that we've seen more papers claiming increase than decrease, at least in LC. Papers suggesting decrease tend to get more air time though as everyone thinks this means dementia, and they start propagating on social media.

There are quite a few structural and functional imaging studies coming through, so it's hard to know which are worthwhile posting as threads. Although I haven't read it I thought this one was worthwhile given it's from a big group.

This one is not yet published —

Multiple Voxel Pattern Analysis Shows Associations Between Chronic Fatigue Syndrome and Cortical Atrophy (2025, Frontiers in Neuroscience)

Here are a few others from the last six months that I don't think have been posted —

Altered corticostriatal connectivity in long-COVID patients is associated with cognitive impairment (2025, Psychological Medicine)

Two-year impact of COVID-19: Longitudinal MRI brain changes and neuropsychiatric trajectories (2025, Psychiatry and Clinical Neurosciences)

Decreases in frequency-dependent intrinsic activity of the default mode network are associated with depression and cognition in patients with postacute sequelae of SARS-CoV-2 infection (2025, Brain Structure and Function)

Executive Function Deficit in Patients with Long COVID Syndrome: A Systematic Review (2025, Heliyon)

Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina (2024, BMC Neurology)

Assessment of Post-COVID-19 Changes in Brain—Clinical and Imaging Evaluation Using MRI Vessel Wall Imaging and Complementary MRI Methods (2024, Journal of Clinical Medicine)

Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection (2024, Nature Scientific Reports)

Sex differences in ACE2, TMPRSS2, and HLA-DQA2 expression in gray matter: Implications for post-COVID-19 neurological symptoms (2024, Preprint: MedRxiv)

Neuroimaging Correlates of Post-COVID-19 Symptoms: A Functional MRI Approach (2024, Diagnostics)

Cerebrovascular Reactivity Assessed by Breath-Hold Functional MRI in Patients with Neurological Post-COVID-19 Syndrome—A Pilot Study (2024, Neurology International)

Comprehensive MRI assessment reveals subtle brain findings in non-hospitalized post-COVID patients with cognitive impairment (2024, Frontiers in Neuroscience)

 

Heh. I've only had a chance to read a couple of those and don't wan't to completely swamp the forum. And at this stage, the big picture I think is that the most we can probably say is that LC and ME/CFS seem to cause measurable brain changes. But a bit like the various and sometimes contradictory metabolic findings, perhaps there's a lot of variation in how individuals or particularly structured cohorts might be responding, either as direct effects or with compensations.

Also all these neuroimaging studies are probably a little removed from what we need to know in terms of actionable causative findings. Other imaging studies such as MR lung perfusion (if validated/replicated), could be a little closer to the action and perhaps point to the upstream processes.

 

I’m reminded of a point Jonathan made elsewhere - they measured different values, not changes. We don’t know what their brains looked like before they got LC.

 

There is the '22 UK Biobank study, though admittedly that was "post-Covid" not "LC".

SARS-CoV-2 is associated with changes in brain structure in UK Biobank (2022, Nature)