Neurocognitive function following out-of-hospital cardiac arrest

Background: The brain is susceptible to hypoxic-ischemic brain injury in conjuction with out-of-hospital cardiac arrest (OHCA). Cognitive impairments are documented in about half of all OHCA survivors, however with a pronounced heterogeneity in measurements and findings. More detailed studies and instruments that are sensitive to OHCA-related cognitive impairment, including predictive models to identify individuals at risk, are needed. It is also unclear how different neurocognitive outcome methods are related to each other, to the brain injury, and to associated factors.Aims: The overall aim of this thesis was to explore the extent of neurocognitive impairment following OHCA in the late recovery phase. Specific aims per papers included in this thesis were: I) To examine the psychometric properties of an observer-reported questionnaire modified for usage after cardiac arrest, the Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE-CA). II) To explore associations between four neurocognitive outcome methods administered in the late recovery phase and early hypoxic-ischemic brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the four outcome methods. III) To describe the rationale and, IV) report initial results of detailed assessment of neurocognitive impairment in OHCA survivors, compare the cognitive performance to a cohort of participants following acute myocardial infarction (MI), and investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors.Methods: I & II) Post-hoc analyses of surviving participants of the international multicenter Target temperature management 33 °C versus 36 °C after out-of-hospital cardiac arrest trial (TTM-trial), its biobank, and its cognitive sub-study, with a follow-up at 6 months post-arrest. III & IV) Prospective inclusion of surviving participants of the international multicenter Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2-trial) at neuropsychological sub-study sites, recruitment of a matched non-arrest control group with acute MI, and an extensive neuropsychological assessment at approximately 7 months post-cardiac event.Results: I) The IQCODE-CA had acceptable psychometric properties and may be used alongside with performance-based measures when screening for post-arrest cognitive impairment. II) The clinician-report Cerebral Performance Category was mostly related to brain injury according to NFL, but with a ceiling effect. Although associations between patient-reports and performance-based measures were weak, all four outcome methods correlated significantly with each other. III & IV) Cognitive impairment on neuropsychological tests was generally mild among OHCA survivors (29% had at least borderline–mild impairment in ≥ 2 cognitive domains, and 14% had major impairment in ≥ 1 cognitive domain), but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. Diabetes and symptoms of anxiety, depression, and fatigue were associated with worse cognitive performance among the OHCA survivors.Conclusions: Cognitive impairment following OHCA is common. A post-OHCA follow-up service should screen for cognitive impairment using different neurocognitive outcome methods with acceptable psychometric properties. Since cognitive impairment is interrelated with emotional problems and fatigue, these areas should also be covered within routine screening. Patients with signs of impairment could be referred to neuropsychological assessment or team-based cognitive rehabilitation programs to optimize their recovery and long-term outcome