Post-COVID microvascular dysfunction in hospitalized [survivors] is associated with [severity] & persistent cognitive complaints, 2025, van der Knaap+

SNT Gatchaman

SNT Gatchaman

Senior Member (Voting Rights)
Staff member
Post-COVID microvascular dysfunction in hospitalized COVID-19 survivors is associated with acute disease severity and persistent cognitive complaints
Noa van der Knaap; Simona Klinkhammer; Alida A. Postma; Johanna M.A. Visser-Meily; Janneke Horn; Caroline M. van Heugten; Paulien H.M. Voorter; Merel M. van der Thiel; Gerhard S. Drenthen; Walter H. Backes; Frank van Rosmalen; Susanne van Santen; Bas C.T. van Bussel; Iwan C.C. van der Horst; David E.J. Linden; Marcel J.H. Ariës; Jacobus F.A. Jansen

OBJECTIVE
Coronavirus disease 2019 (COVID-19) is known to have adverse effects on the brain's vasculature in some patients. After recovery of the infection, vascular abnormalities may persist, but it remains unclear which pathological pathways play a role in post-COVID vascular and cognitive dysfunction and may contribute to post-COVID cognitive complaints.

METHODS
In this observational cohort study, 108 previously hospitalized COVID-19 survivors (general ward: n = 53; intensive care unit (ICU): n = 55) were compared. Cerebral microvascular properties in the cortical gray matter (cGM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH) were assessed using multi-b-value diffusion MRI around 9 months post-infection and related to acute systemic blood markers and post-COVID cognitive performance and complaints.

RESULTS
A lower microvascular perfusion volume fraction (fmv) and blood flow-related measure (fmv·Dmv) were found in ICU compared to general ward patients in the cGM (p = .032; p = .021), NAWM (p = .008; p = .006), and WMH (p = .014; p = .035). No associations were found between diffusion/perfusion metrics and cognitive performance, but a lower fmv in the NAWM was found in those with more cognitive complaints (p = .047). In ICU survivors, higher median blood lactate levels during ICU admission were associated with lower fmv (p = .031) and fmv·Dmv (p = .044) in the NAWM.

INTERPRETATION
Significantly more widespread post-COVID cerebral microvascular dysfunction was found in COVID-19 ICU compared to general ward survivors. Post-COVID microvascular dysfunction in the NAWM may be due to more severe cerebral tissue hypoxia at time of the infection and is associated with persisting subjective cognitive complaints, even in absence of objective cognitive problems.

HIGHLIGHTS

• Multi-b-value diffusion MRI has potential applications in post-COVID assessment.

• Post-COVID cerebral microvascular dysfunction is more severe in ICU survivors.

• Post-COVID microvascular dysfunction may be a result of acute tissue hypoxia.

• Objective cognition is unaffected by post-COVID cerebral microvascular dysfunction.

• Subjective complaints are related to post-COVID cerebral microvascular dysfunction.


Link | PDF (Journal of the Neurological Sciences) [Open Access]
 
SNT Gatchaman said:
• Objective cognition is unaffected by post-COVID cerebral microvascular dysfunction.
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Though they also say:

Objective cognitive dysfunction may emerge only over time, with cognitive complaints potentially preceding future cognitive decline [44]. Hence, 3C-IVIM might be sensitive enough to subtle brain abnormalities that could represent an early preclinical stage of cognitive decline, which could not be detected by neuropsychological tests at the time of assessment.

Our findings highlight the complexity of post-COVID cognitive impairment and the need for longitudinal studies to determine if microvascular dysfunction predicts future cognitive decline and whether 3C-IVIM could serve as an early biomarker for individuals at risk.
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the pre-COVID cerebrovascular disease status for the included patients was unknown, so any pre-existing cerebral abnormalities may have affected our results as this could have led to a bias of patients requiring admission to the ICU
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Absolutely - and also that if someone is experiencing a significant loss of cognitive function compared to how they were before getting ill, it's meaningless to tell them that they are 'objectively' unimpaired because their results are now 'average'.
 
Eleanor said:
Absolutely - and also that if someone is experiencing a significant loss of cognitive function compared to how they were before getting ill, it's meaningless to tell them that they are 'objectively' unimpaired because their results are now 'average'.
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I did a 3 hr neuropsychological assessment less than a year after I got sick. None of the results were below any of the thresholds. I tried to tell him that my head doesn’t work like it used to, but the neuropsych was adamant that I could not have had any loss of cognitive function. It did not surprise me that he later published about psychosomatic explanations for LC brainfog.
 
Further evidence to —

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study (2024, Journal of Cerebral Blood Flow & Metabolism)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection (2024, American Journal of Neuroradiology)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 (2024, Nature Scientific Reports)

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up (2023, Brain Communications)

In sum indicating that normal appearing white matter (NAWM) on routine structural imaging —
  • can be demonstrated to be abnormal with advanced MRI diffusion-weighted imaging protocols
  • which is correlated with subjective cognitive dysfunction (even when routine objective evaluation is normal/insensitive)
I think these white matter microstructural imaging protocols need to move into routine clinical use for targeted assessment (ie indication: brain fog).
 
SNT Gatchaman said:
Further evidence to —

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study (2024, Journal of Cerebral Blood Flow & Metabolism)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection (2024, American Journal of Neuroradiology)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 (2024, Nature Scientific Reports)

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up (2023, Brain Communications)

In sum indicating that normal appearing white matter (NAWM) on routine structural imaging —
  • can be demonstrated to be abnormal with advanced MRI diffusion-weighted imaging protocols
  • which is correlated with subjective cognitive dysfunction (even when routine objective evaluation is normal/insensitive)
I think these white matter microstructural imaging protocols need to move into routine clinical use for targeted assessment (ie indication: brain fog).
Click to expand...
Would this indicate that the non-imaging tools are not sensitive enough to detect e.g. brainfog unless it’s very, very severe?
 
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