Cognitive performance in idiopathic intracranial hypertension and relevance of intracranial pressure

Abstract

Cognitive impairments have been reported in idiopathic intracranial hypertension; however, evidence supporting these deficits is scarce and contributing factors have not been defined. Using a case-control prospective study, we identified multiple domains of deficiency in a cohort of 66 female adult idiopathic intracranial hypertension patients. We identified significantly impaired attention networks (executive function) and sustained attention compared to a body mass index and age matched control group of 25 healthy female participants. We aimed to investigate how cognitive function changed over time and demonstrated that deficits were not permanent. Participants exhibited improvement in several domains including executive function, sustained attention and verbal short-term memory over 12-month follow-up. Improved cognition over time was associated with reduction in intracranial pressure but not body weight. We then evaluated cognition before and after a lumbar puncture with acute reduction in intracranial pressure and noted significant improvement in sustained attention to response task performance. The impact of comorbidities (headache, depression, adiposity and obstructive sleep apnoea) was also explored. We observed that body mass index and the obesity associated cytokine interleukin-6 (serum and cerebrospinal fluid) were not associated with cognitive performance. Headache severity during cognitive testing, co-morbid depression and markers of obstructive sleep apnoea were adversely associated with cognitive performance. Dysregulation of the cortisol generating enzyme 11β hydroxysteroid dehydrogenase type 1 has been observed in idiopathic intracranial hypertension. Elevated cortisol has been associated with impaired cognition. Here, we utilized liquid chromatography-tandem mass spectrometry for multi-steroid profiling in serum and cerebrospinal fluid in idiopathic intracranial hypertension patients. We noted that reduction in the serum cortisol:cortisone ratio in those undergoing bariatric surgery at 12 months was associated with improving verbal working memory. The clinical relevance of cognitive deficits was noted in their significant association with impaired reliability to perform visual field tests, the cornerstone of monitoring vision in idiopathic intracranial hypertension. Our findings propose that cognitive impairment should be accepted as a clinical manifestation of idiopathic intracranial hypertension and impairs the ability to perform visual field testing reliably. Importantly, cognitive deficits can improve over time and with reduction of intracranial pressure. Treating comorbid depression, obstructive sleep apnoea and headache could improve cognitive performance in idiopathic intracranial hypertension.

Keywords: cognition; headache; idiopathic intracranial hypertension; intracranial pressure; visual field.

Graphical Abstract

Figure 1

Cognitive task performance differences between control and IIH participants, baseline and follow-up and pre- and post-lumbar puncture. (A) Sustained attention reaction time is higher in IIH than controls at baseline (434 ms control versus 47s6 ms IIH; P = 0.003). (B) IIH participants made more errors of commission than controls at baseline (proportion correct 0.772 control versus 0.615 IIH; P = 0.031). (C) Reaction times during attention network tests are significantly lower at follow-up than at baseline (baseline 695 ms versus 12 months 657 ms, P = 0.005). (D) Sustained attention reaction times are also reduced at follow-up compared to baseline (baseline 471 ms versus 12 months 447 ms, P < 0.001). (E) Performance in operation span task is improved at follow-up compared to baseline (baseline 0.588 versus 0.650 follow-up, P = <0.001). (F) Sustained attention to response task reaction time is lower post-lumbar puncture than pre-lumbar puncture (baseline 391 ms versus 12 months 354 ms, P = 0.004). Scores expressed as mean (SD) and compared with within/paired or between/unpaired analysis of variance, repeated-measures analysis of variance, t-tests, or z-tests, as appropriate. * = P <0.05, ** = P <0.01, *** = P <0.001.

Figure 2

Correlation between vision measurements, attention network and sustained attention task performance in IIH at baseline. Attention network test and sustained attention to response task times are correlated with HVF measurements in IIH participants. (A) Average attention network test reaction time and HVF false negative. (B) Average attention network test reaction time and HVF false positive. (C) Average attention network test reaction time and visual field index. (D) Average attention network test reaction time and HVF mean deviation. (E) Average attention network test reaction time and test time duration. (F) Sustained attention to response task reaction time and HVF false positive. (G) Sustained attention to response task reaction time and HVF false negative. Non-parametric Spearman’s rank performed to calculate correlation, r and P values. HVF = Humphrey visual field; RT = reaction time.