The effect of middle cerebral artery pulsatility index on cognitive impairment in post-ischemic stroke patient: A case–control study

INTRODUCTION

Clinical manifestations of cerebrovascular diseases, such as stroke, can occur as a cognitive impairment.^[1] It was stated that the risk of a patient developing mild cognitive impairment after stroke or transient ischemic attack is increased and around 35.2% of ischemic stroke patients someday will develop a cognitive impairment.^[2,3] Complete neuropsychology is necessary for diagnosing cognitive impairment and a neuroimaging examination, such as magnetic resonance imaging (MRI), is mandatory to pinpoint the exact brain region that had an infarcted lesion.^[4] Unfortunately, in Indonesia, access to MRI examination is still minimal; thus, an alternative examination is necessary.

Some studies have stated that vascular dysfunction has a very strong relationship with cognitive impairment, and the changes in vessel structures and function play an important role in cognitive decline after a stroke event.^[5] Structural and functional of cerebral vessels can be assessed through transcranial Doppler (TCD) examination. TCD examination is a noninvasive modality to assess intracranial vessels. Many studies have stated that intracranial peripheral resistance strongly correlates with cognitive decline. In one study, it was stated that intracranial peripheral resistance, defined as the pulsatility index (PI) in the Middle Cerebral Artery (MCA), can be used as a predicting factor of cognitive decline in patients with hypertension.^[4] However, in a different study, it was concluded that there was no relationship between MCA in diabetic patients with cognitive declining.^[6]

Indonesia, as a developing nation with a large population, has a significant burden of after-stroke event symptoms. With the increase of cognitive impairment after ischemic stroke events and with the increase of non-communicable diseases in Indonesia, it become mandatory for a rural hospital or clinicians that do not have access to a still considered luxurious neuroimaging examination such as MRI. TCD may serve as an alternative for clinicians to predict cognitive decline in stroke patients. Thus, this study intended to measure the effect of the MCA PI measured by TCD in post-stroke patients with cognitive impairment.

MATERIALS AND METHODS

An observational analytic study with an unmatched case– control design to measure the odds ratio (OR) was performed from January 2022 to April 2022 in Moehammad Hoesin General Hospital Palembang neurology outpatient clinic in post-ischemic stroke patients. Cognitive impairment was measured using the Montreal Cognitive Indonesia Version (Moca-Ina), and then, the participants were divided into a case group and a control group. The permission to use Moca was obtained before the research began. After that, the PI will be measured by a certified neurosonologist for each group. Cognitive assessments were performed in patients who had a first stroke event and approximately 3 months onset. Vascular risk factors, such as hypertension, diabetes, heart dyslipidemia, and coronary artery disease, were also recorded as confounding factors.

RESULTS

There were 58 participants who were divided into 29 controls group and 29 cases group. The demographic and clinical characteristics and their relation with cognitive status are summarized in Table 1.

The most found risk factor in patient post-ischemic patients with cognitive impairment is hypertension (86.2%, P = 0.125) followed by dyslipidemia (65.5%, P = 0.008), with the majority of patients with cognitive impairment within more than 55 years old. (79.3%, P = 0.015) and the most common gender is male (65.5%, P = 1.0).

As seen in Table 2, in total, there were 79.3% (P = 0.015) of patients who were recorded with high PI, which means statistically that there is a relation between high MCA PI and cognitive impairment, and according to the OR measurement, the value was 4.718 with a confidence interval (CI): 1.481–15.032.

After the bivariate analysis was performed, further analysis was carried out to analyze the confounding factors that had P < 0.25 such as age, dyslipidemia, smoking, and hypertension. Logistic regression was performed to observe the interaction between confounding variables and dependent variables. As seen in Table 3, it was concluded that hypertension did not have any interaction and was ruled out in the first regression. After further analysis, the gold standard model was found, such as PI, age, dyslipidemia, and smoking with OR = 4.417 (CI: 1.015–19.218). Hence, it can be concluded that age and dyslipidemia have a major role in post-ischemic stroke cognitive impairment.

DISCUSSION

This study divided the age groups following the previous study, with a cut of 55 years.^[7] The majority of the patients age is within above 55 years old (62.1%). This is similar to the previous study that shows ischemic stroke more often occurred at more than 55 years old in which 62.4%.^[8] Structural changes in the intracranial vessel can inhibit cortical neurovascular coupling that will result in cognitive detoriation.^[8] Male is the most common gender found to have ischemic stroke (65.5%). There is also a similarity with other studies in Indonesia that show males (62.5%) who were more prone to suffer from stroke.^[9] It was stated that females have neuroprotectant factors from estrogen and progesterone.^[10] Stroke incidence in females will increase when menopause starts to occur.^[11] Vascular risk factors such as hypertension and diabetes mellitus also play a big role in vessel remodeling that will speed up vessel degeneration.^[11]

In our study, risk factors that affect cognitive status are age (P = 0.015) and dyslipidemia (P = 0.008). Endotel dysfunction will more that occur due to risk factors that will disrupt the autoregulation and neurovascular coupling mechanism.^[8] Cholesterol plays a big role in the degeneration process of beta-amyloid precursor peptide protein that will cause an accumulation of beta-amyloid peptide in the brain that will speed up the process of cognitive impairment.^[12]

The most common risk factors identified were hypertension (86.2% P = 0.125) and diabetes mellitus (41.4% P = 0.585), although statistically there were no relations found. Differences between risk factors exposure are different and very individualistic dependent that statistically very hard to control and to identify within a specific timeline. This study also only acquire a small number of other risk factors such as coronary artery disease and smoking.

In Table 2, we can conclude that MCA PI effect affected cognitive impairment in post-ischemic stroke patients. In transcranial Doppler examination, PI shows high peripheral resistance that shows microangiopathy changes within intracerebral vessels. Lim et al found that MCI patient who progressed to dementia had high baseline PI.^[13] High PI indicates high peripheral resistance and reflects microangiopathic changes in cerebral blood vessels.^[13] Bieson in his study found that dementia patient has a high PI.^[5] The most common cognitive impairment in post-ischemic stroke patients is very related to the formation of cerebral small-vessel disease (CSVD) and the diagnosis of CSVD requires MRI examination.^[1] Kneihsl et al. stated that the thickening of the aorta will affect arterial systematically and increase intracranial PI that can trigger CSVD.^[14] In Indonesia, access to MRI examination for diagnosing CSVD is still a major problem that can also affect further treatment; thus, PI can be considered for a CSVD and cognitive impairment. Altman has stated that PI can be considered as a reflection of deep intracranial resistance and also affects MMSE score.^[15] Relationships found statistically in this study, which may serve PI to become a predictor of cognitive impairment in post-ischemic stroke events. The limitation of PI is that PI does not always show full vascular resistance that sometimes also affected by systemic hymodinamics.^[14] The Research Process Flowchart is shown in Supplementary File 1

CONCLUSION

Our study suggests that the MCA PI has a relationship to post-ischemic stroke cognitive impairment, and age and dyslipidemia may serve as confounding factors for cognitive impairment.