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Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej
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vol. 14
 
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Review paper

Prediction of cognitive dysfunction after resuscitation – a systematic review

Wioletta A. Mędrzycka-Dąbrowska, Katarzyna Czyż-Szybenbejl, Katarzyna Kwiecień-Jaguś, Katarzyna Lewandowska

Adv Interv Cardiol 2018; 14, 3 (53): 225–232
Online publish date: 2018/09/21
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Introduction

Cardiac arrest (CA) due to cardiovascular disease is the leading cause of death in developed countries [1]. Most cases of CA occur at home, which results in a high level of mortality [2]. It is estimated that over 350,000 people in Europe suffer from out-of-hospital cardiac arrest (OHCA) [3], approximately 186,000 are hospitalized because of CA, more than half of these people die within a year, and about 25,000–40,000 have cognitive impairment [4, 5].
Despite the improvement of resuscitation techniques and post-resuscitation care, the proportion of outcomes remains constant [6]. Cerebral ischemia and hypoxia associated with cardiac arrest cause a number of adverse biomechanical effects. The interruption of the blood supply to the brain (hippocampus, neocortex, medial temporal lobe) that occurs during CA can cause cognitive decline [5, 7–10]. The severity of symptoms depends on the extent of the brain damage, which is directly proportional to the duration of CA [11]. According to the literature, the longer the episode of CA, the greater the risk of cognitive impairment, especially short-term memory, as well as immediate and delayed recall. Other common dysfunctions include attention deficits and executive function disorders [12]. The neurological and cognitive status is the most important factor affecting the overall quality of life. Patients with prompt resuscitation who respond to stimuli after return of spontaneous circulation (ROSC) or follow instructions within 6–12 h after CA have a high probability of full recovery or only minor impairment of cognitive function. Amongst patients in a coma lasting 1–7 days, the occurrence and prevalence of cognitive impairment is uncertain, while a coma lasting more than 7 days after ROSC is associated with a bad neurological prognosis [3, 13].

MethodsSearch strategy

The electronic databases PubMed/MEDLINE, OVID, Web of Science, and EBSCO were searched using the following key words: ‘sudden cardiac arrest’, ‘out-of-hospital cardiac arrest’, ‘cognitive function’, ‘cognitive impairment’, ‘cognition’, ‘functional outcome’, ‘cardiopulmonary resuscitation’ and ‘neuropsychological tests’. The most recent studies from the last 7 years (2011–2018) were included. The search was limited to human studies that were published in English or in Polish languages. Individual keywords or their combinations were typed during the search, using the AND, OR operators, or both. The number of publications obtained in each search was filtered taking into account the inclusion criteria, i.e. patients after sudden cardiac arrest who have undergone cognitive assessment, which allowed a core/primary database to be created for the study. In the next step the abstracts and summaries were arbitrarily limited to selected articles. Finally, references and bibliographies of those articles were analyzed to broaden the original searches and the final list of references was created based on the relevance of the topic discussed.

Study selection

The review included studies on cognitive functioning after CA in adults. The following articles were excluded:
– articles published in languages other than English and Polish;
– studies with subsequent cognitive status testing repeated within 1 month;
– research on patients with brain damage;
– studies describing the same or overlapping patient sample; in this case, we used the latest article, which described both new data and data previously reported;
– studies with missing data which were crucial for the review.
The studies’ eligibility was assessed on the basis of the title, summary and, if necessary, the full text, by two reviewers using the aforementioned selection criteria.

Data extraction

Both reviewers independently evaluated selected articles using a standardized data collection form (Table I) [5, 11, 12, 14–19]. Characteristics were as follows: first author, year of publication, study design, population, number of participants, average age at the beginning of the study, duration of resuscitation, time interval after CA followed by cognitive tests, in which there was a cognitive impairment, the result of cognitive impairment and the proportion of patients with cognitive impairment. The quality of the study was evaluated based on four criteria:
1) the availability of cognitive performance data at the beginning of the study;
2) the use of neuropsychological tests to assess cognition (Table II) [20–48];
3) description of inclusion and exclusion criteria;
4) the impact of factors that could interfere with the cognitive outcome, such as age and sex.
These qualitative criteria were chosen because they are widely used (criteria 3 and 4) and are specific to the study evaluating neurocognitive outcome (criteria 1 and 2).

Results and discussion

The results published by different authors vary significantly. Cognitive disorders occurred in a broad range of cases: from 13% (Lilja et al.) to even 100% (Alexander et al.) [14, 19]. In one study, cognitive deficits did not occur at all (Raina et al.) [15]. Such a significant difference could have been influenced by the quality and quantity of tests used to assess cognitive functions. Alexander et al. used a significant number of tests, which had an impact on the high level of detection of cognitive impairment [19]. In contrast, Raina et al., who did not observe any cognitive impairment, used Mini-Mental State Examination (MMSE) and Telephone Interview Cognitive Status (TICS) to assess cognitive functions [15]. Nevertheless the use of MMSE does not guarantee accurate results [49]. In an earlier study Cronberg et al. drew attention to the fact that tests such as MMSE may be insufficiently sensitive for patients with preserved intellectual capacity [50].
Amongst the reviewed articles only two studies were carried out on a large group of patients (287 Lilja et al., 249 Beesems et al.) [17]. The remaining studies were conducted on a small group of respondents [14, 29, 30, 41], so there was no possibility to generalize the results to the entire population. Some authors compared the results of OHCA patients to healthy controls matched for age, sex (Beesems et al., Tiainen et al.) as well as education (Jaszke-Psonka et al.) [12]. The control group should not be composed of healthy people because it can lead to impairment exaggeration. Instead, it should rather include controls matched for risk factors, not age or gender only [19]. Buanes et al. used norms for healthy populations of other countries due to the lack of Norwegian standards. Raina et al. did not compare the obtained results to any control group. Lilja et al. compared their results to STEMI controls treated with percutaneous coronary intervention (matched for age, gender, country and time-point of hospitalization), whereas Alexander et al. [14, 19]. chose controls with acute coronary syndrome matched for age, gender, education, risk factors, previous cardiac events and the use of psychoactive medication.
The areas in which the most cognitive impairment occurred were memory [5, 11, 12, 14, 16, 19], executive functions and visual–motor skills [11, 12, 14, 16, 19], which is consistent with earlier studies: Lim et al. reported that the most common pattern of impairment in their patients was a combination of memory and motor deficits with variable executive impairment [51]; Sauve et al. found in their study that 72% of those subjected to cognitive tests after CA had worse memory scores (especially delayed recall) [52]. Cronberg et al. obtained similar results – the majority of patients (62%) showed memory impairment of varying severity [10], which may have been the result of the susceptibility of the hippocampus to ischemia. However, not only patients after CA are at risk of cognitive impairment – concordant results were obtained when conducting tests on a group of patients hospitalized in Intensive Care Units or undergoing surgical procedures [53, 54]. Some patients diagnosed with cognitive disorders after CA might have had them before the incident. Therefore, it can be concluded that CA does not lead to specific changes in cognitive functioning. Due to the sudden and unpredictable nature of out-of-hospital cardiac arrest, it is difficult to assess the level of cognitive functioning before the incident. Lilja et al. reported that only half of the presented executive dysfunctions could have been caused by CA, which was confirmed by the STEMI controls results (attention and mental speed were the most affected among CA patients, whereas results for executive functioning and memory were comparable).
Cardiac arrest and the subsequent loss of blood flow through the brain tissue cause a number of biochemical changes resulting in brain damage. So far, several studies have shown that the use of therapeutic hypothermia (TH) after CA had a protective effect on brain tissue [55–57]. Therapeutic hypothermia is recommended for all patients with shockable cardiac rhythm who remain unconscious after ROSC [58]. Most of the studies included in the review did not show significant differences in cognitive function between TH patients and those who did not receive TH [14, 16, 17]. However, Alexander et al. concluded that their results may indicate effectiveness of therapeutic hypothermia, because TH patients had a lower level of cognitive impairment. Orbo et al. concluded that TH was a stronger predictor compared with coma duration for performance on the executive function tests – hypothermia treatment predicted better cognitive results. However, in a prior study Cronberg et al. indicated a high incidence of cognitive impairment in patients undergoing TH.
Knowing the influence of prolonged hypoxia on the central nervous system, it can be assumed that the shorter the period from cardiac arrest to ROSC or full consciousness is, the better the cognitive performance results will be. Orbo et al. and Jaszke-Psonka et al. did not confirm such a relationship. Weigl et al. studied individuals who experienced short CA during cardiac procedures and concluded that even a short episode of hypoxia could be the cause of cognitive decline [59]. However, Alexander et al. reported that patients who regained consciousness quickly (1–3 days) were more likely to present mild cognitive impairment (33%) in comparison to the patients who needed more time to recover (3–7 days) and were much more cognitively impaired (67%). This is in line with the previous studies: Sauve et al. suggested in their study that the persistency of cognitive disorders after CA may be estimated based on the duration of the unconsciousness period. Groswasser et al. noted better results of cognitive tests when the coma lasted less than 24 h from the occurrence of anoxic brain injury [60].
It can be hypothesised that the longer recovery after CA is, the better the cognitive functioning will be amongst the patients. Beesems et al. did not confirm this hypothesis, explaining it by the lack of daily challenges in hospital conditions, which would require the use of certain cognitive processes. In a small prospective study Lim et al. reported that impairments in memory and executive functioning remained the same, but there was a modest reduction in the number of patients with impairments in other domains (comparing outcomes at 3 and 12 months) [61]. Polanowska et al. reported that cognitive impairment occurred in all patients 3 days after the OHCA incident, whereas after 12 months the impairment was present in 57.2%. In this study an alarmingly large group of patients suffered from neurological disorders (including the vegetative state). After 12 months cognitive testing was performed on 14 patients, while 29 entered the study. Reviewers found this study to be of poor quality.
Previously Hofgren et al. used cognitive tests and the Activities of Daily Living scale (ADLs) in CA survivors 2 years after the incident: recovery of cognitive functions to the expected level was not attained as only one person achieved a score equal to the cut-off results. It should be noted, however, that the level of cognitive functioning alone is not the most important element, because patients learn to cope with cognitive limitations over time and manage to live independently [15, 62]. Moderate cognitive impairment is not always connected with dependence or disability [16]. Apart from the cognitive status, several authors tested the level of independence (functional outcome) [15, 19] and the quality of life [15–17, 19]. For patients after CA independence in their environment and return to work are important, because it affects mood and the occurrence of depressive symptoms [15]. However, the occurrence of depression affects the results of cognitive tests [12], the process of rehabilitation [15] and the quality of life [63].

Conclusions and therapeutic implications

Cognitive impairment four years after CA seems to be comparable to early Alzheimer’s dementia [5]. It seems that this mainly affects memory, with little effect on executive functions. Thus self-awareness of the occurrence of cognitive deficits is important because it allows new strategies to be developed for dealing with various challenges, including return to work.
One conclusion derived from reviewing the literature is the importance of continuous training of cognitive functions, especially for people with cardiovascular risk. In this group of patients, qualified neuropsychological care and rehabilitation focused on the training of cognitive functions should be provided. Future studies should provide information about selection of tests most suitable for cognitive impairment screening. It is important to achieve a level of independence after CA that allows patients to return to work, which has a positive psychological effect. It was established that CA survivors may experience symptoms of depression for several months after the incident [15]. Therefore, caregivers for patients after CA should be able to assess the mood of the care recipients, because depression affects the rehabilitation process, and thus the level of independence [15, 45, 63].

Conflict of interest

The authors declare no conflict of interest.

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