Correlation Between Cognitive Impairment During The Acute Phase Of First-ever Cerebral Infarction And Development Of Long-term Pseudobulbar Affect

BackgroundIschemic cerebral stroke is a disease with high morbidity,high death rate and high disability rate.Pseudobulbar affect(PBA)is very common in patients with ischemic cerebral stroke and its major clinical characteristics refer to frequent and transient uncontrollable outbursts of crying or/and laughter which may be exaggerated or incongruent with the underlying emotional state.It not only influences neurological function rehabilitation after ischemic cerebral stroke,but also intervenes patients' daily life and social interactions,obstructing patients' rehabilitation process in integrating social role which deserves attention.Therefore,exploration of predictors of post-infarction PBA for early targeted intervention is very significant.However,PBA still continues to be underdiagnosed and undertreated at present,which put great burdens on families and society.By reviewing the past prospective studies and cross-sectional studies,we found that PBA may occur in association with cognitive impairment in some neurodegenetive diseases,such as amyotrophic lateral sclerosis and multiple sclerosis.However,during the clinical practice,people tend to pay more attention to cognitive disorder which could be screened out in early stage.So,the study on the relationship between cognitive impairment during the acute phase of first-ever cerebral infarction and the development of long-term pseudobulbar affect can enrich clinical diagnosis and treatment of pseudobulbar affect,which is helpful for practical management of physicians.But till now,there are rare research reports at home in this issue.The nested case-control study recombine case-control study and cohort study to form a new composite epidemiological design whereby a case-control approach is employed within an established cohort.Compared with case-control study,nested case-control study collects clinical data first,thus reducing temporal ambiguity and recall bias,and can save cost and time compared with cohort study.ObjectiveThis study aims to detect a cause-and-effect relationship between cognitive impairment during the acute phase of first-ever cerebral infarction and the development of long-term pseudobulbar affect,for the purpose of determining correlation between their clinical management.By this study,we try to provide a scientific basis for identifying the population at risk of PBA and strengthening the preventive measures.Patients and methodsThe data were collected in prospective follow-up survey.We conducted a longitudinal study of the first-ever cerebral infarction cohort in Shandong Province,China.The cohort included 202 patients in two medical centers.The cases who were unable to complete neuropsychological tests due to various reasons,who had previous cerebral infarction,cognitive decline or other diseases and those with drug abuse or medications likely to influence the results were excluded in this cohort.Finally,a total of 157 study participants were recruited in this study.Baseline clinical data were collected from these patients who all completed neuropsychological tests.All study participants were invited for follow-up.We conducted visits by phone or outpatient follow-up.The discharge date of these patients was used as the start date of follow-up visit for each patient.Follow-up time was limited between 2015.10.07 and 2017.2,28.Because of the small sample size and limitation of manpower and material resources,nested case control study was carried out.First,we set up the study cohort of first-ever cerebral infarction.The diagnostic criteria for PBA were as follows:(1)excessive or inappropriate laughing,crying,or both compared with their premorbid state occurring after acute phase of cerebral infarction;(2)the symptoms lasting for at least 2 weeks;(3)a total PLC scale score of 13 or higher;(4)uncontrolled crying or laughing that could not be explained by other neurological or psychological disease;(5)no history of PBA.Newly diagnosed PBA cases were classified into the case group at the end of follow-up.We then randomly selected controls from the first-ever infarction patients who remained free from PBA and matched them to the case patients in a 1:1 ratio,according to age,sex and education background.On this basis,patients with cognitive impairment according to MoCA(Montreal cognitive assessment)scores during the acute phase of first-ever infarction would be set as new study cohort.Patients who suffered from PBA after follow-up visit would be also classified into the case group,we randomly selected matched controls from the post-infarction cognitive impairment cohort.Then,related risks factors for long-term PBA in patients with cognitive impairment and features of cognitive domain would be analyzed.Results1.Establishment of first-ever cerebral infarction nested case-control study cohort.The population in this study was selected from patients with a first-ever symptomatic cerebral infarction.By comprehensive evaluation,one hundred and fifty seven patients were included in this study to do the follow-up visit.Finally,patients who suffered from recurrent cerebral infarction or comorbidity or who couldn't be reached for visit were excluded.As of 28 february,2017,137 cases were followed up,20 cases lost follow up,median follow-up time was 6(0.9-9.5)months.Of the 137 patients with first-ever cerebral infarction who received follow-up,31(27.1%)had pseudobulbar affect during non-acute phase(case group),and we then randomly selected controls from among the post-infarction cognitive impairment patients who remained free from PBA and matched them to the case patients in a 1:1 ratio,according to the internal control condition.A total of 62 patients were included in nested case-control study.2.Characteristics of the cohort coupled with the correlation between cognitive impairment and pseudobulbar affect.Among the first-ever cerebral infarction nested case-control study cohort,32 were males(51.61%)and 30 were females(48.39%)with a male-to-female ratio of 1.07:1.The age ranged from 38 to 75,with an average of 62.10±8.21,and the education years were 0-13 years,7.27±2.95 years on average.The MoCA scores were used as the criterion for cognitive impairment in the acute stage of cerebral infarction.22 cases(70.97%)experienced cognitive impairment in the case group,and 9(29.03%)in the control group.Analysis of risk factors associated with PBA in patients with first-ever cerebral infarction showed statistically significant difference in the proportion of patients with cognitive impairment between the two groups.The incidence of PBA during the non-acute phase of cerebral infarction was significantly correlated with acute-phase cognitive impairment(OR,5.975,95%CI,1,995-17:893,P = 0.002),There were no significant differences involving other risk factors between the two groups.3.Establishment of post-infarction cognitive impairment nested case-control study cohort.Risk factors for PBA development in patients with cognitive impairment.Based on these findings above,a second nested case-control study was conducted,with MoCA scores adopted as the criterion for acute-phase post-infarction cognitive impairment.Of the 157 patients with first-ever cerebral infarction,109 patients were diagnosed with post-infarction cognitive impairment,accounting for 69.43%.Of the 109 patients with acute-phase cognitive impairment of first-ever cerebral infarction,96 patients received follow-up.Of the 96 patients,31(27.1%)had pseudobulbar affect during non-acute phase(case group),and we thenrandomly selected controls from among the post-infarction cognitive impairment patients who remained free from PBA and matched them to the case patients in a 1:1 ratio,according to internal control condition.A total of 52 patients were included in nested case-control study.Among them,24 were males(46.15%)and 28 were females(53.85%)with a male-to-female ratio of 0.86:1.The age ranged from 38 to 75,with an average of 62.06±7.50,and the education years were 0-13 years,7.38±2.80 years on average.Single factor analysis of risk factor for long term PBA in patients with post-infarction cognitive impairment indicated that proportion of patients whose infarction sites were both in the frontal lobe and basal ganglia region was higher(26.92%vs 3.85%,P<0.05)and scores of MoC A and Mini-Mental State Examination(MMSE)test in case group were obvious lower than those in the control group.Subgroup analysis of cognitive function in each cognitive domain between case group and control group was further carried out for comparison.These neuropsychological tests covered four cognitive domains.Scores of neuropsychological tests in case group showed that more time was required to complete StroopC examination(P<0.05)and more missing and errors were seen in clock drawing test(CDT)and digit span test(DST).The difference was significant(P<0.05).Taking the genesis of PBA as dependent variable,results of condition logistic regression analysis of baseline factors demonstrated that after adjusting potential confounding factors,lower MoCA?MMSE scores in the acute stage of cerebral infarction were still the independent determinant for the incidence of long term PBA in patients with posts-infarction cognitive impairment.Results of cognitive domain subgroup analysis indicated that overlong StroopC time,lower DST scores and CDT scores were independent risk factors for long term PBA in patients with post-infarction cognitive impairment.Conclusions1.Compared with normal cognitive ability,cognitive impairment during the acute phase of first-ever cerebral infarction increase risk for developing long term PBA.There was significant correlation between the existence of cognitive impairment and pseudobulbar affect.2.The severity of post infarction cognitive impairment was the independent risk factor for PBA in patients with cognitive impairment.Lower MMSE?MoCA scores were predictive factors for the incidence of pseudobulbar affect.3.Subgroup analysis of cognitive domain showed that patients with visuospatial deficit,executive dysfunction,and attention deficit during the acute phase had relatively high incidence of long-term PBA after cerebral infarction,which was of predictive significance.Frontal lobe lesion might play an important role in the relationship between cognitive domain and pseudobulbar affect.4.Neuropsychological tests scores could be reference in predictingPBA.Due to fewer research cases,larger samples and in-depth researches were necessary to verify this results.