Dementia Could Occur Due to Long-term Effects of Mini Strokes

Highlights

• Decline of cognitive function has been found to be linked to cerebrovascular diseases such as atherosclerosis and cerebral amyloid angiopathy.
• Studies have shown that occurrence of microinfarcts is markedly higher in patients with dementia and cognitive decline.
• Mechanism by which these microinfarcts lead to cognitive impairment has not been well understood.
• This study aims to determine how microinfarcts may contribute to dementia and cognitive impairment.

Microinfarcts (vascular lesions measuring 0.05 -3mm in diameter) can lead to functional deficits that are larger than expected and could last for much longer than previously thought. In effect these observations might possibly enhance the occurrence of dementia and cognitive decline, according to recent research conducted at the Medical University of South Carolina (MUSC).

Aim of the Study

The study wished to determine how mini-strokes could cause dementia and cognitive impairment, the mechanisms of which remain poorly outlined.

This assessment was made more difficult by the fact that microinfarcts are difficult to diagnose by standard available neuroimaging techniques. In addition, there has been poor correlation between clinical functional deficit and post-mortem microscopic evidence making it extremely difficult to link microinfarcts to the timeline of cognitive decline and intellectual impairment.

"These infarcts are so small and unpredictable, we just haven't had good tools to detect them while the person was still alive," said Andy Shih, Ph.D., Assistant Professor of Neurosciences and senior author on the article. "So, until now, we basically just had post-mortem snapshots of these infarcts at the end of the dementia battle as well as measures of the person's cognitive decline, which might have been taken years before the brain became available for study."

Hypothesis of the Study

The research team embarked their study based on the hypothesis that the extent of functional deficit caused by the microinfarcts could actually be larger than the evidence offered by microscopy or radiological imaging such as magnetic resonance imaging (MRI).

"Even though a person may experience hundreds of thousands of microinfarcts in their lifetime, each event is extremely small and thought to resolve in a matter of days," said Shih. "It's been estimated that, overall, microinfarcts affect less than 2% of the entire human brain. But those estimates of tissue loss are based only on the 'core' of the microinfarct, the area of dead or dying tissue that we can see in routine, post-mortem, histological stains."

Details of the Study

The research team developed a mouse model to assess the effects of individual cortical microinfarcts on brain function over several weeks following the occurrence of the microinfarct. This would enable creation of lesions that could be followed up over a period of time and to obtain printouts of brain activity that were well-defined over a period.

Advertisement

Employing photothrombosis, the team occluded a single vessel in the barrel cortex of mice that were fitted with cranial windows. The resultant functional deficit was measured by sensory evoked brain activity measured by activity-related c-Fos expression or in vivo two-photon imaging of single vessel hemodynamic responses and correlated with the location and size of the core of the microinfarct.

Results of the Study

• Post-mortem c-Fos immunostaining indicated that the area affected by the microinfarct was least 12 times greater in volume than the microinfarct core.
• In vivo, two-photon imaging of single vessel hemodynamic response elicited by sensory stimulation, estimated that neuronal activity in the affected region was depressed for up to 14 to 17 days after the microinfarct.

Together, the results show that functional deficits caused by a single microinfarct involves a much larger area around the lesion than was previously thought and that the resulting deficits last much longer.

Advertisement

"The MRI signal increased and then went away as we'd expected, but we were surprised on autopsy to see that there was still lots going on --tissue damage and neuroinflammation," Shih explained. "Even after three weeks the neurally evoked blood flow responses had only partially recovered. So, that means a microinfarct can come and go and you can see it briefly with MRI but it leaves a lasting impression on brain function-possibly for months."

According to Shih, the cumulative effects of multiple microinfarcts suffered over a period of time could actually equal the impact of a single large infarct.

Takeaway from the Study

• The authors feel that standard available methods employed do not reveal the true extent of the damage caused by microinfarcts.

Dr Shih hopes that the findings of their study would help clinicians in the interpretation of MRI and help researchers better correlate their findings in studies conducted.

• The findings of the study could lead to the establishment of newer preventive protocols.

"On a clinical level, maybe it's a situation where therapeutics can play a bigger role. Maybe drugs that we already have can mitigate the cumulative damage of microinfarcts," speculated Shih. "The neuro-protective idea hasn't flown very far for acute stroke, in part, because the window of time for protecting the brain from stroke damage is very narrow. But, for microinfarcts, you don't have to know exactly when they occur. If an MRI shows a person is at high risk for microinfarcts, maybe one day we can put them on a drug for a while to reduce the impacts of these lesions."

References: https://www.eurekalert.org/emb_releases/2017-01/muos-tle011117.php

Source-Medindia