Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment, July 2023, Bestecher et al

[EndME]

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment

Abstract
As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients. To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment.

Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26).

These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNg, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment. We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors.

This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.


Preprint uploaded to medRvix: https://www.medrxiv.org/content/10.1101/2023.07.21.23292988v1

 

[SNT Gatchaman]

We identified clusters of cortical thickness alterations in both hemispheres with higher cortical thickness moving from healthy, never infected controls with lowest cortical thickness to healthy COVID-19 survivors to patients without and finally patients with cognitive impairment according to MoCA.

It should, however be acknowledged that there are also studies reporting a decrease in GMV or cortical thickness in post-COVID patients or healthy COVID-19 survivors compared to non-infected controls. The most eminent study is the longitudinal thickness analysis in the UK Biobank sample, reporting cortical thinning in survivors of COVID-19. Since cortical thickness is highly dependent on age, it is noteworthy that the sample was 10 years older on average than our cohort and that cortical alterations were not connected to clinical symptom severity.

Papers I've seen discussing grey matter decrease or increase post Covid are —

Decreased
Covid-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study (2023, Preprint: MedRxiv)
Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome (2023, Lancet: eBioMedicine)
Multivariate prediction of long COVID headache in adolescents using gray matter structural MRI features (2023, Frontiers in Human Neuroscience)
Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers” (2023, BMC Neurology)
SARS-CoV-2 is associated with changes in brain structure in UK Biobank (2022, Nature)

Increased
This preprint.
Larger gray matter volumes in neuropsychiatric long-COVID syndrome (2022, Psychiatry Research)

 

[SNT Gatchaman]

Published as —

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment
Besteher; Rocktäschel; Garza; Machnik; Ballez; Helbing; Finke; Reuken; Güllmar; Gaser; Walter; Opel; Rita Dunay

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.

To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls (n=30), healthy COVID-19 survivors (n=29), and subgroups of long-COVID patients with (n=26) and without (n=35) cognitive impairment according to screening with Montreal Cognitive Assessment. Wholebrain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry.

We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFN, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.

We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

Link | PDF (Brain, Behavior, and Immunity)

 

[dave30th]

how do the FND and functional cognitive disorder people respond to this?

 

[SNT Gatchaman]

Well it's all neuroplasticity of course.

In The neuroimaging evidence of brain abnormalities in functional movement disorders (2021, Brain) —

Morphometric MRI has detected changes in regions associated with emotional processing, suggesting stress-mediated neuroplasticity in individuals with functional weakness. Individuals with FMDs demonstrate an increased volume of the left amygdala, striatum, cerebellum, fusiform gyrus and bilateral thalamus but this does not correlate with duration or severity of the presenting illness. It is unclear whether these represent premorbid characteristics that make these individuals susceptible to FMDs, or if they occur as a consequence of it.

Referencing Gray matter differences in patients with functional movement disorders (2018, Neurology) —

To shed further light on possible neuroanatomical differences in patients with FND, we recruited 48 patients with functional movement disorders (FMD), a subset of FND characterized by abnormal involuntary movements, and 55 matched healthy controls (HCs) as part of an observational study including neuroimaging. We hypothesized that patients with FMD would exhibit altered gray matter volume (GMV) when compared with HCs, as has been demonstrated in patients with other FNDs.

patients with FMD exhibited greater GMV compared to HCs in the left amygdala, left putamen, left caudate, left cerebellum, left parahippocampal gyrus, left fusiform gyrus, and bilateral thalami, including the medial dorsal and ventral lateral nuclei. Patients with FMD had reduced GMV of the left precentral and postcentral gyri. We did not detect between-group differences in total GM or white matter volume.

Our results demonstrate abnormalities in GMV in critical components of the limbic and motor circuitry in patients with FMD. It remains unclear whether these structural findings are a cause or consequence of the disorder; these structural abnormalities could represent a premorbid trait predisposing patients to disease, the disease itself, or an adaptive response to disease. The recent finding that children with FND also exhibit volumetric differences, in the absence of the psychiatric comorbidities and long history of medication use often seen in adult cohorts, supports the idea that abnormalities in brain structure in FND may be intrinsic to the disease or experience-dependent plasticity inherent to the disease. Longitudinal studies tracking patients’ symptoms in addition to structural and functional neuroimaging data, both over time as well as in response to successful treatment regimens, may help to address this important question.

Referencing Grey matter abnormalities in children and adolescents with functional neurological symptom disorder (2017, NeuroImage: Clinical) —

In conclusion, our data provide evidence of early structural alterations in the SMA, STG, and DMPFC in children/adolescents with functional neurological symptom disorder. These brain regions are involved in the processing of facial expressions of emotion and facilitate a timely, accurate assessment of, and response to, the emotional states of others. Larger volume in these regions may reflect both the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness in the context of adverse life events and long-standing relational stress.

 

[Sean]

We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups,

Dose-response relationships are usually good evidence.

 

[Jonathan Edwards]

how do the FND and functional cognitive disorder people respond to this?

Probably much as I do - it is difficult to know what on earth it might mean. Thicker cortex usually means healthier. Maybe more intelligent people are more likely to report brain fog after Covid.

 

[rvallee]

Well it's all neuroplasticity of course.

In The neuroimaging evidence of brain abnormalities in functional movement disorders (2021, Brain) —



Referencing Gray matter differences in patients with functional movement disorders (2018, Neurology) —







Referencing Grey matter abnormalities in children and adolescents with functional neurological symptom disorder (2017, NeuroImage: Clinical) —

Good grief this is pure fanaticism. They define the whole thing as the absence of "structural" changes, therefore psychological, and when they find some they just attribute them to psychological processes, even in children, who didn't even live long enough for it to apply. The framing of vigilance makes no sense whatsoever, it's just belief support belief.