Host‐Microbial Cometabolite Ursodeoxycholic Acid Protects Against Poststroke Cognitive Impairment

 If your competent? doctor isn't actively researching cognitive impairment fixes; you DON'T have a functioning stroke doctor! Don't know what it is, but it's NOT a doctor! Proof that you don't have a doctor is NO followup with human testing!

cognitive impairment (110 posts to January 2019)

cognitive decline (315 posts to December 2011)

50% cognitive impairment (2 posts to September 2021)

24 to 70% post-stroke cognitive impairment (2 posts to November 2019)

Host‐Microbial Cometabolite Ursodeoxycholic Acid Protects Against Poststroke Cognitive Impairment

Xuxuan Gao, MD https://orcid.org/0009-0007-5558-7012, Feng Zhang, MD, Jiafeng Zhang, MSc, Yu Ma, MSc, Yiting Deng, MD https://orcid.org/0009-0001-4927-6003, Jiaying Chen, MD, Yueran Ren, MD, Huidi Wang, MD, Boxin Zhao, PhD https://orcid.org/0000-0003-3574-0511 zhaobx@smu.edu.cn, Yan He, PhD https://orcid.org/0000-0002-6611-2959 yanhe@smu.edu.cn, and Jia Yin, MD https://orcid.org/0000-0001-8944-6604 yinj@smu.edu.cnAuthor Info & Affiliations

Journal of the American Heart Association

New online

https://doi.org/10.1161/JAHA.124.038862

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Abstract

Background

Poststroke cognitive impairment (PSCI) is a common residual disability after stroke, often underestimated and underdiagnosed. We previously found that ursodeoxycholic acid (UDCA), a host‐microbiota cometabolite, ameliorates brain damage in stroke mice. Based on these findings, we aimed to evaluate the predictive value of UDCA for PSCI risk in a prospective cohort study.

Methods and Results

We recruited 202 patients with mild acute ischemic stroke and 63 patients with symptomatic large‐artery atherosclerotic stenosis as the modeling and external validation cohorts, respectively. Mice were subjected to transient middle cerebral artery occlusion, and cognitive function was assessed using the Morris water maze test. Patients with mild acute ischemic stroke who developed PSCI exhibited significant alterations in gut microbiota and plasma bile acid profiles during the acute stroke phase, including a notable reduction in UDCA level. Through feature selection and machine learning, we constructed a predictive model for PSCI incorporating plasma UDCA level, the relative abundance of Clostridia, Bacilli, and Bacteroides, as well as age, educational level, and the presence of moderate to severe white matter lesions. This model exhibited robust predictive performance in both internal (area under the curve, 0.904 [95% CI, 0.808–1.000]) and external (area under the curve, 0.838 [95% CI, 0.742–0.934]) validations. Animal studies in mice also showed reduced UDCA levels in plasma and brain tissue following stroke. UDCA administration improved cognitive function in stroke mice by reducing hippocampal microglial activation and neuronal apoptosis.

Conclusions

Our findings indicate that UDCA has potential as a biomarker for predicting PSCI risk and plays a neuroprotective role in the progression of PSCI. This suggests that early identification and intervention targeting UDCA could represent a promising strategy for the prevention and treatment of PSCI.

Graphical Abstract

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis

 You blithering idiots, survivors don't want predictions of cognitive impairment, they want prevention of that. Do you even have two neurons to rub together to think at all? When 50% of survivors have cognitive impairment, don't you think just maybe you should solve that problem?  I'd have you all fired.

Oops, I'm not playing by the polite rules of Dale Carnegie,  'How to Win Friends and Influence People'. 

Telling supposedly smart stroke medical persons they know nothing about stroke is a no-no even if it is true. 

Politeness will never solve anything in stroke. Yes, I'm a bomb thrower and proud of it. Someday a stroke 'leader' will try to ream me out for making them look bad by being truthful, I look forward to that day.

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis 

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Emily Louise Ball, Mahnoor Shah, Eilidh Ross, ...

First Published August 4, 2022 Research Article 

https://doi.org/10.1177/17474930221120349

Article information

Abstract

Background:

Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset.

Aim:

This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia), on magnetic resonance imaging (MRI) performed at stroke diagnosis.

Summary of review:

We searched the literature from inception to January 2022 and identified 10,284 records. We included studies that performed MRI at the time of stroke (0-30 days after a stroke) and assessed cognitive outcome at least three months after stroke. We synthesised findings from 26 papers, comprising 27 stroke-populations (N=13,114, average age range=40-80 years, 19-62% female). When data were available, we pooled unadjusted (ORu) and adjusted (ORa) odds ratios.

We found associations between cognitive outcomes and presence of cerebral atrophy (3 studies, N=453, ORu=2.48, 95%CI=1.15-4.62), presence of microbleeds (2 studies, N=9151, ORa=1.36, 95%CI=1.08-1.70), and increasing severity of white matter hyperintensities (3 studies, N=704, ORa=1.26, 95%CI=1.06-1.49). Increasing cerebral small vessel disease score was associated with cognitive outcome following unadjusted analysis only (2 studies, N=499, ORu=1.34, 95%CI=1.12-1.61; 3 studies, N=950, ORa=1.23, 95%CI=0.96-1.57). Associations remained after controlling for pre-stroke cognitive impairment. We did not find associations between other stroke features and cognitive outcome, or there were insufficient data.

Conclusions:

Acute stroke MRI features may enable healthcare professionals to identify patients at risk of post-stroke cognitive problems. However, there is still substantial uncertainty about the prognostic utility of acute MRI for this.

Keywords

Stroke, Cognitive impairment, Dementia, Neuroimaging, MRI, Post-stroke cognitive impairment

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Patients who develop cognitive impairment had changes in the brain before their stroke

This changes nothing; it is still your doctor's responsibility to bring your cognition back to normal.

My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing. I have zero cognitive impairment.

Patients who develop cognitive impairment had changes in the brain before their stroke

by University of Oslo

Figure 1. Examples of stroke lesion segmentation. Examples of voxel-based segmentation of stroke lesions in MNI space, as shown in the coronal, sagittal, and horizontal plane. Color map depicts a larger number of voxels and thus also a larger stroke increasing from red to yellow. Credit: DOI: 10.3389/fnagi.2021.705889

Stroke is caused by disturbances in the blood circulation of the brain due to blood clots or cerebral hemorrhage. This causes damage to parts of the brain, and the patient experiences a sudden loss of particular body functions. Individuals affected by stroke need urgent, life-saving treatment followed by rehabilitation. In Norway, stroke affects approximately 12,000 people each year.

"It appears that about 50 percent of stroke patients get some form of cognitive impairment after the stroke," says Till Schellhorn, who has written his doctoral thesis at the Institute of Clinical Medicine based on the Nor-COAST study.

Cognitive impairment means that an individual's ability to think and to perform intellectual and mental processes has been reduced.

Identifying at-risk patients using MRI images

The researchers examined the brains of patients who developed cognitive impairment after stroke using MRI images. MRI stands for magnetic resonance imaging, and is a method used to take pictures of the body's internal organs.

"Using MRI images of the brain, we can identify risk patients for the development of cognitive impairment after stroke with good certainty," says the researcher.

The MRI images showed that patients who develop cognitive impairment after stroke already had brain changes prior to the stroke that may be associated with the development of cognitive impairment.

"It was mainly the case for patients with small vessel disease, who have a reduced circulation in the small blood vessels in the brain. This can lead to many small cerebral infarctions, and was associated with the development of cognitive impairment after stroke," Schellhorn explains.

Furthermore, the results showed that the size of the stroke was associated with increased risk of developing cognitive impairment. The larger the stroke, the higher the risk of developing cognitive impairment afterwards.

There was also an association between loss of substance in the temporal lobe, which is a part of the brain associated with memory, and the development of cognitive impairment.

"But this association was less pronounced than we had expected," he points out.

Has put cognitive impairment after stroke on the agenda—The Nor-COAST study has put cognitive impairment after stroke on the agenda. In the past, the focus has mostly been on paralysis and other physical ailments, and therefore cognitive impairment has received little attention, Schellhorn explains, and adds:

"But cognitive function means a great deal for the quality of life, both of the patient and their families."

The researchers have set themselves the goals of contributing to more knowledge about the causes of cognitive impairment and developing methods for identifying at-risk patients.

"You have to know whom, and why the individual patient develops cognitive impairment in order to be able to start a treatment," he points out.

Aim for better preventive measures and treatment: "We hope that our research can lead to better treatment of cognitive impairment after stroke in the future. We hope that we can prevent and alleviate cognitive impairment," Schellhorn says.

The researchers are now testing potential preventive measures and novel forms of treatment.

"This could entail preventive treatment among stroke patients with a high risk of developing cognitive impairment, or treatment of the causes, such as cardiovascular disease," the researcher says.

Schellhorn further states that increased physical or social activity as part of rehabilitation after a stroke might slow down the development of cognitive impairment.

A model for clinical use

Eight hundred and fifteen stroke patients were included in the study. The researchers took MRI images of the brain of 410 of them.

The researchers examined these images thoroughly. On the MRI images, which were taken after the stroke, they could see which patients had changes in the brain that had been present already prior to the stroke. To do this, they used different types of MRI images, some that show that brain changes are acute and some that show brain changes of older date.

"It is a combination of specific MRI technique and interpretation that helps us say something about the age of the brain changes," Schellhorn points out.

The researchers believe that some of these changes in the brain were related to the development of cognitive impairment after stroke.

"We investigated the association between the image findings and cognitive impairment. We created a model for predicting the risk of cognitive impairment based on the findings on the images," Schellhorn explains.

So far, the model has only be

en tested within the scope of the Nor-COAST study, but the researchers already have plans to test it on more stroke patients. However, there are also a number of practical challenges that must be solved before the model can be used in a clinical context, i.e. for use in connection with the treatment of patients.

"Before using new computer programs at the hospital, the models must go through a routine security check. Such things typically take some time. But I hope that we can use our models in the clinic at the hospital over the next two to three years."

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More information: Eva Birgitte Aamodt et al, Predicting the Emergence of Major Neurocognitive Disorder Within Three Months After a Stroke, Frontiers in Aging Neuroscience (2021). DOI: 10.3389/fnagi.2021.705889

Provided by University of Oslo