1 Neuropsychological Outcome After Cardiac Arrest: Results from a Sub-study of the Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) Trial
Authors: Nordström Erik Blennow , Vestberg Susanna , Evald Lars , Mion Marco , Segerström Magnus , Ullen Susann , Bro-Jeppesen John , Friberg Hans , Heimburg Katarina , Grejs Anders M. , Keeble Thomas R. , Kirkegaard Hans , Ljung Hanna , Rose Sofia , Wise Matthew P. , Rylander Christian , Unden Johan , Nielsen Niklas , Cronberg Tobias , Lilja Gisela 
Published: December 2023

Objective:To describe cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.Participants and Methods:This was a prospective case control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. We administered an extensive neuropsychological assessment at approximately 7 months post-cardiac event, including a neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Z-scores of individual tests were converted to neuropsychological composite scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions). Between-group differences on the neuropsychological composite scores were investigated with linear regression. Associations between anxiety, depression, fatigue, insomnia, hypertension, diabetes, and the neuropsychological composite scores among OHCA survivors were calculated with Spearman’s rho.Results:Of 184 eligible OHCA survivors, 108 were included (mean age = 62, 88% male), with 92 MI controls enrolled (mean age = 64, 89% male). Amongst OHCA survivors, 29% performed z <-1 indicating at least borderline-mild impairment in >2 cognitive domains, and 14% performed z <-2 exhibiting major impairment in >1 cognitive domain. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = -0.37, 95% confidence intervals [-0.61, -0.12]), verbal (MD = -0.34 [-0.62, -0.07]), and visual/constructive functions (MD = -0.26 [-0.47, -0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, processing speed (MD = -0.41 [-0.74, -0.09]) and executive functions (MD = -0.69 [-1.13, -0.24]) were also worse following OHCA. Depressive symptoms were associated with worse executive functions (rs = -0.37, p <0.001) and worse processing speed (rs = -0.27, p = 0.01) post-OHCA. Anxiety symptoms (rs = -0.21, p = 0.01) and general fatigue (rs = -0.24, p = 0.01) were associated with worse executive functions. Diabetes was associated with worse processing speed (rs = -0.20, p = 0.03), visual/constructive (rs = -0.29, p <0.001) and executive functions (rs = -0.25, p = 0.02), while hypertension and insomnia were not significantly associated with neuropsychological test performance.Conclusions:Cognitive impairment is generally mild following OHCA, but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. We suggest that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.