Poststroke cognitive impairment (PSCI) involves deficits in memory, comprehension, perception, language, and executive function (1). In the past 10 years, PSCI has been the subject of much attention, as it leads to poor life quality, slow functional recovery, and higher mortality. Current evidence suggests that PSCI occurs is about two-thirds of patients during the acute phase of ischemic stroke (2), and that 20–30% of patients with PSCI will develop dementia (3).

Multiple factors have been found to lead to progression of cognitive impairment and dementia after stroke. These include older age, family history, genetic variations, poor educational status, vascular comorbidities, and depression (4). Recently, a cohort study of 6,506 elderly individuals who were followed up for 8 years indicated that an increase of 1 SD in the coefficient of variability of systolic blood pressure (SBP) or diastolic blood pressure (DBP) is associated with an increase of about 10% in the risk of dementia (5). Higher visit-to-visit blood pressure variability (BPV) has also been proved to be associated with cognitive function impairment in the elderly (6). BPV has also been shown to be associated with neurological impairment (7), progression of brain white matter lesions (8), hemorrhagic transformation after ischemic stroke (9), and poor long-term prognosis (10). However, it is still unclear whether higher BPV is a cause or consequence of PSCI.

Poststroke cognitive impairment is not a unitary disease, but involves deficits in multiple domains. However, prospective follow-up studies regarding long-term domain-specific cognitive impairments are rare (11). The aim of this study was to investigate the relationship between BPV and PSCI and the prevalence of domain-specific cognitive impairment.

Our findings suggest that high midterm BPV within 7 days of stroke onset is independently associated with an increased risk for PSCI 3 months after the stroke. Our findings also indicate that male sex, low education levels, high NIHSS scores, cortical–subcortical infarction, and subcortical infarction are risk factor for PSCI. In contrast, cardioembolism of TOAST classification has no effects on cognitive impairment after stroke.

Blood pressure variability is a complex phenomenon that includes short-term fluctuations occurring within a 24-h period, midterm fluctuations over different days, and blood pressure changes over weeks, months, and even years (24). These variations in BP are thought to be the result of complex interactions between extrinsic environmental and behavioral factors and intrinsic cardiovascular regulatory mechanisms (central neural, reflexive neural, and humoral influences) that are not yet completely understood (15). Most importantly, high short-term BPV is a predictor of target organ damage and future cardiovascular events (25, 26). High midterm SBP variability in daytime was a predictor of cardiovascular and all-cause mortality (27). In addition, a recent study has reported that higher midterm BPV was associated with progression of brain white matter lesions and lower cognitive function (28). The authors of the above study suggest that higher BPV is a risk factor for lower hippocampal volume and cerebral mircobleeds independent of average systolic and DBPs. In some analyses, therefore, the predictive value of BPV is even greater than that of average BP during treatment.

A recently study reported an increase in the incidence of stroke in China (29), which may result in an increased prevalence of PSCI. In our study, the incidence of PSCI reached its peak 3 months after ischemic stroke onset. Changes in the incidence of PSCI have an inverse relationship with MoCA scores. Consistent with our findings, the incidence of cognitive impairment 3 months after ischemic stroke was reported to be 71% in a study of 409 middle age and elderly patients with cerebral infarction (10). However, in the hospital-based cohort studies of Ihle-Hansen et al. (30) and Kandiah et al. (31), the incidence of PSCI was 37.5% 1 year after stroke and 37.32% 6 months after stroke. The broad range of reported PSCI incidence may be mainly attributed to differences in race, age, education level, location of stroke, and evaluation methods. We found that the prevalence of PSCI reaches its peak 3 months after stroke and decreases thereafter. It is, however, still unclear whether this trend is a consequence of transient cerebral function disorders and the recovery of stress injury.

The relationship between variability in blood pressure during the acute phase of ischemic stroke and lower cognitive performance 3 months after stroke onset was assessed using multiple parameter logistic regression analysis in our study. Independently of the confounding factors, SBP variability, but not DBP variability, was found to significantly predict the occurrence of cognitive decline. Consistent with our results, a recent epidemiological study (32) reported that day-to-day variability in SBP is significantly related to cognitive impairment (OR, 1.51; p = 0.02). In a study of 353 people, McDonald et al. (33) found that daytime variability in blood pressure is independently associated with greater decreases in total Cambridge Cognitive Examination and Mini-Mental State Examination scores after 5 years of fellow-up. Qin et al. (34) have suggested that higher visit-to-visit variability in systolic BP, but not mean systolic BP, is a predictor of cognitive decline. This stronger relationship can be explained by the fact that more information is provided by measuring the variability of BP than mean BP (35). In addition, the white-coat effect can be eliminated (36) and more target organ damage can be revealed than when using conventional BP measurements (37). However, Kilander et al. (38) suggested 24-h SBP was not associated with cognition. Other study of community-living adults also found no association between SBP and cognitive function (39). It may be explain from it, community-living adults were better able to automatically adjust the effect of systemic SBP on cerebral blood perfusion, which keep them with better baseline perfusion. Some studies have found higher DBP variability was related to poorer cognitive function (40), whereas in other studies no associated between variability in DBP and cognitive function was found (41). However, in our study, higher variability in DBP did not seem to be protective for cognitive decline.

Nevertheless, the potential mechanism for the relationship between high BPV and cognitive impairment is still unclear. Recently, a study demonstrated that higher variability in BP, especially in SBP, can predict the progress of arteriosclerosis (42), lead to subcortical lesions (43), and contribute to the pathogenesis of cerebral vascular disease (44). All of the above factors may have negative impacts on cognitive function. Most importantly, hypertension and further decreases in blood pressure may reduce the coupling efficiency of the neurovasculature and impair dynamic cerebral autoregulation, which would then result in cerebral hypoperfusion. This may then lead to neurological impairment (45) and lead to progressive neurodegeneration (46). Considering energy requirements and blood supply, result in a neuronal energy crisis and cerebral hypometabolism, which may in turn lead to Alzheimer’s disease-related pathology (47).

Sub-analysis of the MoCA scale scores indicated that scores in the visuoperceptual and executive functions domains, as well as those for delayed recall, were decreased in individuals with high BPV. This suggests that visuoperceptual abilities, executive function, and delayed recall are more vulnerable than other domains of cognition. Consistent with our findings, a recent study showed that basal ganglionic lacunar infarcts and cerebral small vessel injuries are related to dysfunctions in delayed memory (48, 49). In addition, periventricular white matter hyperintensities have significant associations with executive function deficits (50). Using the same cohort as that used here, we have previously reported that patients with large artery atherosclerosis based on TOAST classification have lower scores in the visuoperceptual ability and executive function, and delayed recall and attention domains after correction for covariables (51). The potential mechanisms underlying poststroke cognitive decline are still unclear, although the cerebral cortex and hippocampus are sensitive to cerebral ischemia and anoxia (52), which may be a potential mechanism for impairment of visuoperceptual abilities, executive function, and delayed recall after stroke.

We also observed that cortical–subcortical and subcortical infarctions are more likely to lead to PSCI. Our results are in agreement with those of Hilal et al., who, in a study of 550 patients, reported that subcortical gray matter atrophy, such as that indicated by lacunes and white matter lesions, is not only observed in dementia but is also found in the preclinical stages of cognitive impairment (53). Rocque et al. reported that patients with large carotid plaques are more likely to have cognitive impairment (54). Pathophysiologically, multi-vessel, extracranial atherosclerotic disease may cause chronic diffuse brain hypoperfusion, which may be associated with cognitive impairment (55).

Our study has some limitations. First, only ages between 40 and 75 years were included in our study and other inclusion and exclusion criteria operated will influence BP variability and could weaken the external validity of results. Second, the use of different antihypertensive agents and other medications may have affected the variability in blood pressure and the relationship between BPV and poststroke cognition. What’s more, the study also had selection bias, as only hospitalized patients were enrolled, although this was inevitable. Another limitation of this study is that obstructive sleep apnea, which is associated with both BPV and cognitive dysfunction, could not be measured.

Higher midterm SBP variability during the acute stage of cerebral infarction was found to be associated prospectively and independently with increased risk of PSCI, especially in the domains of executive function, naming, and delayed recall. This highlights the need for neurologists to pay more attention to the variability of blood pressure in patients with acute ischemic stroke. Population-based prospective studies are required to confirm our conclusions.

Study on optimizing control strategy of blood pressure for the prevention of stroke in rural community. Ethical Review and Approval Documents. Our hospital is to carry out “Study on optimizing control strategy of blood pressure for the prevention of stroke in rural community,” the ethics committee of our hospital has a review of relative medical ethics issue of the project.

Conceptualization: SG, NL, PM, NJ, and MH. Data curation: SG and MH. Formal analysis: SG and MH. Investigation: YS, YX, BX, ZL, XN, YZ, CX, and XZ. Methodology: SG, NL, PM, and MH. Project administration: SG, NL, PM, NJ, and MH. Resources: SG, NL, PM, NJ, YS, YX, GZ, XH, ZC, BW, BX, ZL, XN, YZ, CX, and XZ. Software: SG and NL. Supervision: SG and MH. Validation: GS, NL, PM, NJ, MH, YS, YX, GZ, XH, and ZC. Visualization: SG and NL. Writing—original draft: SG. Writing—review and editing: SG and MH.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.