Effectiveness of the Second-Stage Rehabilitation in Stroke Patients With Cognitive Impairment

Summary. The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients.Material and Methods. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of Rehabilitation, Hospital of Lithuanian University of Health Sciences . Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. Results. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status significantly associated with hemiplegia (OR, P=0.015), urinary incontinence P<0.001), diseases P=0.022), heart P=0.041), severe cognitive impairment P<0.001), moderate and mild cognitive impairment was not associated with the recovery of functional status. Conclusions. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment.


Introduction
Majority of stroke patients have motor, cognitive, and behavioral disorders during the subacute stage (1)(2)(3)(4)(5). Cognitive impairment is diagnosed in 21.8% to 65% of stroke patients during the subacute stage (4,(6)(7)(8)(9) and in nearly one-third of stroke patients during the later stages of the disease (10). The literature shows that cognitive and emotional outcome in stroke patients depends on a combination of 3 factors. First, the localization of lesion in gray matter determines selective impairments. Second, diffuse neuronal dysfunction determines mental speed, memory disorders, and reduced executive functioning. Third, the degree of cognitive outcome presumably depends on such factors as patient's age, gender, premorbid level of functioning, and comorbidities. They are the objects of future research (11).
Cognitive and motor impairments can infl uence the recovery of functional status in stroke patients during rehabilitation (1,4,8,(12)(13)(14)(15), make worse the course of rehabilitation (4), extend the duration of rehabilitation (5,14) as well as have a negative impact on independence in daily activities and quality of life (4,16). Recently, the studies are being carried out on factors that could predict functional recovery during rehabilitation in stroke patients. Mostly they consider age, gender, type of stroke, motor disorders, and comorbidities as the factors infl uencing the effectiveness of rehabilitation (1,13,14,17,18). However, the studies on the impact of cognitive impairment on the recovery of functional status in stroke patients are lacking. Moreover, the results on associations between cognitive impairment and effectiveness of rehabilitation are ambiguous and sometimes even contradicting.
The aim of our study was to evaluate the recovery of functional status and the effectiveness of the second-stage rehabilitation (subacute stage of disease) depending on the degree of cognitive impairment in stroke patients.

Material and Methods
The study included stroke patients who underwent rehabilitation at the Viršužiglis Hospital of Rehabilitation (Hospital of Lithuanian University of Health Sciences) during 2004-2007. The study was approved by the Kaunas Regional Ethics Committee for Biomedical Research. The inclusion criteria were as follows: 1) ischemic stroke, 2) hemorrhagic stroke, 3) stable health status, and 4) ability to tolerate complex measures of rehabilitation 2-3 hours daily. The exclusion criteria were the following: 1) subarachnoid hemorrhage, and 2) severe status due to comorbidities (dementia, severe heart or renal failure, serious neurological or connective tissue disorders, etc.).
Of the 302 stroke patients, 226 met the inclusion criteria. Based on the study protocol, patients' age, gender, social factors (living conditions, family status, occupation, and education), type of stroke, localization of stroke, degree of stroke, clinical symptoms, psychoemotional status, risk factors, and comorbidities were evaluated as well as functional status during the second-stage rehabilitation.
The general functional status, motor and cognitive skills, and their recovery were evaluated using the Functional Independence Measure (FIM). The scale included the motor (13 items) and cognition (5 items) subscales. The motor subscale included the following: 1) eating, 2) personal hygiene, 3) bathing, 4) dressing lower body, 5) dressing upper body, 6) toileting, 7) bladder management, 8) bowel management, 9) transfer to bed, chair, or wheelchair, 10) transfer to toilet, 11) transfer to tub or shower, 12) locomotion (walk or wheelchair), and 13) locomotion (stairs). The motor subscale ranges in score from 13 to 91. The cognition subscale included the following: 1) comprehension, 2) expression, 3) social interaction, 4) problem solving, and 5) memory. The cognition subscale ranges in score from 5 to 35. Altogether, the total FIM score ranges from 18 to 126. The severity of neurologic condition was estimated based on the National Institutes of Health Stroke Scale (NIHSS). The cognitive function was evaluated using the Mini-Mental Status Examination (MMSE), where orientation (time and place), attention, language, short-term memory, calculation, and complex commands are considered. This scale is a reliable, valid, and standardized measure of mental functions, which is widely used both in clinical practice and multicenter trials. The MMSE score ranges from 0 and 30.
At the beginning of the second-stage rehabilitation, the patients were divided into 4 study groups based on cognitive function (MMSE): group 1, severe cognitive impairment (score from 0 to 10); group 2, moderate cognitive impairment (score from 11 to 20); group 3, mild cognitive impairment (score from 21 to 24), and group 4, no cognitive impairment (score from 25 to 30).
Based on every patient's functional status, the individually adjusted rehabilitation program was set and conducted by rehabilitation team. The complex rehabilitation included medication, physical therapy (twice daily), occupational therapy, functional muscular electrostimulation, therapeutic massage, speech correction, and consultations with a psychologist, a social worker, and an orthopedist. The rehabilitation program was applied 6 days a week. The mean duration of the second-stage rehabilitation was 38.8 days (SD, 8.9); the mean time from stroke to the study beginning was 16.9 days (SD, 11.1).
The analysis included comparison of demographic and clinical data, motor and cognitive skills, and general functional status in 4 study groups. The effectiveness of rehabilitation was evaluated based on change in the FIM score during the follow-up. The effectiveness was considered insuffi cient if the FIM score was 18-72 (need for another person's assistance).
Similarly, age, gender, social factors (living conditions, family status, education, and occupation), clinical symptoms, psychoemotional factors, risk factors of stroke, comorbidities, type of stroke, localization of stroke, and degree of stroke were analyzed depending on functional status and recovery.
Statistical data analysis was performed using the SPSS for Windows 13.0 statistical package. For continuous variables, the mean and standard deviation (SD) were calculated. The normality of continuous variables was tested by the Kolmogorov-Smirnov test. In cases of suffi cient sample and normal distribution, the comparison of means of two independent samples was evaluated by the Student t test. In cases of insuffi cient samples (n<20), nonparametric variables or nonnormal distribution, the comparison of two means was evaluated by the Mann-Whitney U test. Likewise, the means of two dependent samples were compared by the Student t test (normal distribution) and Wilcoxon test (nonnormal distribution). Comparison of means of several groups was based on analysis of variance (ANOVA) and Fisher exact test. For comparison of qualitative variables, the chi-square test (χ 2 ) was used.
The impact of covariates on the effectiveness of rehabilitation was estimated using the univariate and multivariate logistic regression analysis, indicating the odds ratios (OR) and confi dence inter-vals (CI). Univariate logistic regression revealed the factors (covariates) that were associated with insuffi cient effectiveness of rehabilitation and they were then included to multivariate logistic regression. The sets of covariates were selected for correlation based on determination coeffi cient R 2 and goodness of fi t based on χ 2 .

Results
The demographic and clinical characteristics of the study population are presented in Table 1. Altogether, there were 226 patients (109 men and 117 women). Cognitive impairment was documented in 120 patients (53.1%). Among them, 41 cases (34.2%) were found to have mild dysfunction, 39 cases (32.5%) moderate impairment, and 40 cases (33.3%) severe impairment. No cognitive impairment was observed in 106 patients (46.9%). The majority (61.5%) of study subjects were elderly patients (aged 65 years and more); the mean age of the study population was 67.8 years (SD, 10.4). These patients mainly suffered ischemic stroke (88.5%).
FIM measurements revealed that the majority of patients needed a moderate or even maximal assistance of another person at the baseline (mean FIM score, 65.9 [SD, 20.3]). At the baseline, cognitive skills measured by the FIM showed a prevailing need of moderate assistance (mean FIM score, 21.6 [SD, 7.5]). The mean MMSE score in the study sample was 20.3 (SD, 9.3). The patients with cognitive impairment were more likely to be elder (P=0.007), female (P=0.041), and with lower education (P=0.002).
Comparison of the degree of cognitive impairment and risk factors of stroke demonstrated that the patients with moderate or severe cognitive impairment were more likely to have atrial fi brillation (P=0.043) and heart failure (P=0.015) as well as to be smokers (P=0.012) compared with patients with mild or no cognitive impairment.
The study found that 9.7% of patients suffered a recurrent stroke. Stroke reoccurred more often in the patients with moderate or severe cognitive impairment than in the patients with mild or no cognitive impairment (P=0.037). However, the data analysis showed that the type of stroke was not associated with the degree of cognitive impairment.
Lesions of the left hemisphere were signifi cantly more often documented in the patients with severe, moderate, and mild cognitive impairment than in the patients without cognitive impairment (87.5%, 53.8%, 48.8%, and 32.1%, respectively; P<0.001).

<0.001
Values are number (percentage) unless otherwise indicated. The analysis of stroke symptoms and neurological status revealed that the patients with poor neurological status more frequently had worse cognitive impairment (P=0.001). Moreover, the patients with cognitive impairment were signifi cantly more likely to suffer urinary incontinence (P<0.001), unilateral neglect syndrome (P=0.001), and depression (P=0.001) ( Table 2).
The recovery of patients' functional status during the second-stage rehabilitation depending on the degree of cognitive impairment is presented in Table 3. At the baseline, poorer cognitive impairment was signifi cantly associated with poorer general functional status as well as poorer cognitive and motor skills (P<0.001). Nevertheless, during the second-stage rehabilitation, all these features -general functional status, motor skills, and cognitive skills -showed an improvement as measured by the FIM (P<0.001).
The changes in general functional status, motor skills, and cognitive skills as of FIM were similar in all 4 study groups. However, the patients with severe and moderate cognitive impairment showed a signifi cantly greater improvement in cognitive skills than those with with mild or no cognitive impairment (P<0.001).
The multivariate logistic regression analysis demonstrated that insuffi cient recovery of general functional status as measured by the FIM was more likely to occur in the patients with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), and heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001) ( Table 4). Meanwhile, mild and moderate cognitive impairment as well as localization of lesion, dysphagia, hemiparesis, and unilateral neglect syndrome did not have a negative impact on the recovery of functional status during the second-stage rehabilitation.

Discussion
Our study is one of the fi rst studies evaluating the effectiveness of rehabilitation depending on the degree of cognitive impairment. The impact of cognitive impairment on the improvement of general functional state, motor skills, and cognitive skills in stroke patients as well as factors predicting the recovery during the second-stage rehabilitation have been identifi ed.
Previous literature shows that cognitive impairment mainly manifests in disorders of orientation, memory, attention, perception, and language (8,(19)(20)(21), and it has a negative impact on daily activities and patient's independence level (3,4,(12)(13)(14)22) and increases the prevalence of depression (9). Our study demonstrated that at the beginning of the   Several studies analyzing the associations between neurological status or functional status and the degree of cognitive impairment have been carried out (12,23). Rabadi et al. evaluated the infl uence of cognitive impairment on the effectiveness of rehabilitation in stroke patients and found that the patients with cognitive impairment had a signifi cantly worse neurological and general functional status at the beginning of rehabilitation, though the researchers did not fi nd any association between cognitive function and motor function impairments (3). Some other studies did not fi nd any association between cognitive and motor function impairments either (4,15). Paolucci et al. aimed to evaluate the infl uence of aphasia on the effectiveness of rehabilitation in stroke patients and noted that the patients with language and perception disorders had a signifi cantly worse neurological and general functional status at the beginning of rehabilitation and had worse recovery of functional status and mobility during the rehabilitation compared with the patients with no language and perception disorders or only with language disorders (21). Wee et al. found that aphasia and other cognitive impairments correlated with the lower FIM scores at discharge after in-patient rehabilitation (14). Other researchers found that the duration of rehabilitation in the patients with no cognitive impairment was shorter and they were more likely to be discharged from hospital compared with the patients with diagnosed cognitive impairment (3). Our study showed that the patients with moderate or severe cognitive impairment at the beginning of the second-stage rehabilitation had a worse neurological and general functional status throughout the whole study compared with the patients with mild or no cognitive impairment at the baseline. The results of our study together with the results from other studies showed that the patients with severe or moderate cognitive impairment had a signifi cantly better progress of cognitive function during the second-stage rehabilitation compared with the patients with mild or no cognitive impairment.
There are published studies that analyzed the impact of cognitive impairment on functional status improvement in stroke patients and provided ambiguous results. Rabadi et al. conducted the study aiming to establish whether the rehabilitation was effective in stroke patients with cognitive impairment. They surveyed 668 patients during the rehabilitation and revealed that general functional status measured by the FIM improved signifi cantly regardless of the degree of cognitive impairment; additionally, they did not fi nd signifi cant differences in improvement between patients with and without cognitive impairment (3). Heruti et al. also noted that the degree of cognitive impairment did not infl uence the change of functional status during the rehabilitation (12  gated the impact of cognition and depression on functional status and its recovery after 6 months in stroke patients and found that better improvement and recovery of functional status was signifi cantly infl uenced by less expressed depression and its alleviation, neurological status and its improvement, better functional status and younger age at onset, but not by cognitive function or its change (24). Hama et al. analyzed the impact of depression and apathy on the recovery of functional status and found that the MMSE score and Apathy scale score were negatively associated with the improvement of functional status during the rehabilitation in stroke patients, while there were no associations between depression and function status (22). Zinn et al. conducted a prospective cohort study aiming to evaluate the association between cognitive impairment and recovery of functional status and found that the patients who suffered cognitive impairment had poorer recovery of daily activities 6 months following the rehabilitation as measured by the Lawton test (4). Our results demonstrate that the patients with cognitive impairment experience a signifi cant improvement in general functional status and motor skills during the second-stage rehabilitation similarly like the patients without cognitive impairment. Moreover, both general functional status and motor skills measured by the FIM improved during the second-stage rehabilitation to similar extent in all study groups (regardless of the degree of cognitive dysfunction).
There are ambiguous results in the literature about the impact of cognitive function on functional status outcomes in stroke patients. Heruti et al. studied the recovery of functional status in elderly patients and found that poorer recovery of motor skills and general functional status measured by the FIM were infl uenced by cognitive impairment diagnosed at the beginning of rehabilitation (12). Zinn et al. revealed that cognitive impairment increased the likelihood of insuffi cient functional status recovery 4-fold, while the association of cognitive impairment with insuffi cient recovery of motor skills was not signifi cant (4). In contrast, Meijer et al. investigated various factors and their impact on the recovery of functional status during the subacute stage of stroke and found that cognitive impairment was the main factor predicting poor outcomes of stroke (25). Paolucci et al. pointed that language and perception disorder was a signifi cant predictive factor for the effectiveness of rehabilitation, since it increased the likelihood of poor recovery of functional status 4-fold (21). Other researchers note that aphasia as a signifi cant disorder of cognitive function has also an impact on the recovery of functional status in stroke patients and leads to poorer disease outcomes (14,21,26,27). Ones et al. investigated the associations between age, gender, diabetes, primary functional status, cognitive functions, degree of motor dysfunction, spasticity at the beginning of rehabilitation, and functional status at the end of rehabilitation. They found that the recovery of general functional status and motor skills measured by FIM were associated with age, spasticity, functional status, cognitive function, and motor skills at start of rehabilitation, but gender and diabetes were not associated with functional status after rehabilitation (1). Oksala et al. conducted the study analyzing the long-term survival in stroke patients depending on cognitive impairment. The analysis of 12-year follow-up showed that impairments in executive functions, language, memory, and visuospatial/constructional skills were associated with poorer disease outcomes (8). Paker et al. analyzed the impact of cognitive impairment on the recovery of functional status measured by the Barthel index in stroke patients and found that rehabilitation was effective in subacute stroke patients both with and without cognitive impairment (23).
Our multivariate logistic regression revealed that insuffi cient general functional status was more likely to be documented in patients with hemiplegia, urinary incontinence, joint diseases, heart diseases, and severe cognitive impairment. Meanwhile, mild or moderate cognitive impairment was shown to have no signifi cant predictive value on insuffi cient recovery of general functional status and motor skills during the second-stage rehabilitation. The discrepancy between our results and results from the previous studies could be explained by sample differences in age distribution, disease duration until rehabilitation, degree of cognitive impairment, degree of neurological and functional status at the beginning of rehabilitation as well as differences in evaluation criteria and methods for effectiveness.

Conclusions
During the second-stage rehabilitation, functional status as well as cognitive and motor skills improved both in stroke patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment. The insuffi cient recovery of functional status during the second-stage rehabilitation in stroke patients was found to be infl uenced by hemiplegia, urinary incontinence, joint diseases, heart diseases, and severe cognitive impairment, while the moderate and mild cognitive impairment did not have such a negative impact on the recovery of functional status.

Statement of Conflict of Interest
The authors state no confl ict of interest.