SCCM Resource Library-04-Association of Plasma Insulin Growth Factor to Memory and Cognition 12 Months After Aneurysmal SAH

Video Transcription

Hi, my name is Elizabeth Crago, and I'm an assistant professor of nursing at the University of Pittsburgh.  I will be presenting our research, Association of Plasma Insulin Growth Factor to Memory and Cognition, 12 Months After Aneurysmal Subarachnoid Hemorrhage.  I would like to thank the Society of Critical Care Medicine and the program committee for the honor and opportunity to speak with you today.  And I would like to acknowledge the other members of my research team at the University of Pittsburgh, and now the University of Texas Austin, as Dr. Poliak has moved there after  this abstract was completed and accepted. I have no disclosures, and this work was funded by NIH grants.  Subarachnoid hemorrhage is an often devastating event occurring in six to nine per 100,000 persons. 85% of subarachnoid hemorrhage is a result of ruptured cerebral aneurysms.  While survival rates have improved, up to 75% of survivors suffer permanent cognitive deficits, including 60% with memory deficits and 75% with language deficits.  While these deficits may improve in the months after discharge, studies report continued memory up to 50% and language up to 15% deficits one year out.  Self-reported measures are often higher, up to 95% describe mental slowness, short-term memory problems, and attention deficits.  Importantly, this significantly affects the ability to return to productive and functional  life, including return to work, and exacerbates depression, anxiety, fatigue, and sleep symptoms.  Insulin growth factor is a potent cellular growth-promoting factor that is clearly essential for normal development of the central nervous system.  IGF has also demonstrated independent neuroprotective actions in stroke and neurologic disease, and has been linked to memory and cognitive performance.  IGF-1 is associated with hippocampal volume, and lower serum IGF-1 has been implicated in age-related cognitive decline, diabetes dementia, and Alzheimer's disease, as well  as hypertension and inflammation. Specifically in stroke, IGF has been associated with infarct volume, but important to this  discussion, higher serum IGF levels have been positively associated with post-stroke outcomes. The purpose of this analysis was to examine the relationship between mean plasma IGF-1  levels after subarachnoid hemorrhage, and cognitive performance in measures of executive function, learning, and memory 12 months after SAH.  This cohort of 130 aneurysmal subarachnoid hemorrhage survivors were obtained from an existing NIH study of patients aged 21 to 75 years with a ruptured cerebral aneurysm  resulting in a Fisher score greater of two or more. No patients with chronic neuro-debilitating diseases or non-aneurysmal subarachnoid hemorrhage were enrolled.  Demographics and SAH-specific scoring, in this case the WFNS, were obtained from the patient, patient surrogate, and the medical record.  Plasma samples were collected and stored daily from consent through 14 days after hemorrhage as available.  IGF-1 concentrations were then derived from those stored plasma samples, a total of 1,221, using a commercial solid phase ELISA kit, and then mean plasma IGF-1 concentrations  for each patient were calculated. Quality measures including duplicate samples and standard curves were used with each plate analysis.  NP assessments, which covered seven domains, were completed at 12 months during a face-to-face interview with the patient.  Learning and memory was measured with the Wechsler Logical Memory Subtest and the Ray  Complex and Tay Figure copy immediate and delayed recalls, and the digit span forward and backward.  The memory subtest assessed short and long-term recall of stories, both immediate and a 30-minute delay.  The digit span requires the participant to listen to a series of numbers given by the interviewer and then repeat the series of numbers in the same order, first in forward  progression and later in a reverse order. Cognitive function and mental flexibility were measured with the Trailmaking Test A  and B, which is a white sheet of paper that consists of numbers and letters. Initially, they do the numbers in sequential, and then they are asked to do the numbers  in letters together in sequential. The Stroop Color Award Test consists of three sections, which increase in complexity, first  identifying colors, then reading, and then reading with the ability to ignore the color of the letters.  Language was measured with the Controlled Oral Word Association and the Animal Naming Test.  The color is a test of participants' ability to create as many words as possible with either the letters F, A, or S within one minute.  They make accounts for repetition or use of the same root more than once, or also mistakes. Nonparametric correlations were completed using Spearman's Row, and linear regression  was used to analyze the continuous outcome measures to the mean IGF-1 measurements. The cohort of 130 ASAH survivors were predominantly female, 79%, with a mean age of 54.1 years.  These are both common in SAH populations. The mean WFNS was 1.8, with over 79% having a grade 1 or 2. Remember, these were survivors as we were looking at long-term outcomes.  Common correlations demonstrated associations between mean IGF-1 levels and older age, where IGF-1 levels were lower in older patients.  This is an expected finding, as this is also present in healthy population. Of interest, WFNS and BMI were not associated with mean IGF-1.  Mean IGF-1 levels were also associated with poor memory performance on all of the TAE  the copy, the immediate, and the delay recall, as well as the logical memory subskill. Mean IGF-1 levels were also associated with poor performance on the WAIS test, which looks  at executive functioning using the TRAILS A and B. Because the outcome variables were continuous, again, a linear regression model controlling  for age and WFNS was used to further examine these relationships between mean IGF-1 and outcome variables.  Mean IGF-1 remained significantly associated with measures of poor memory performance, including all of the TAE figure measures, copy, immediate, and delay, as well as logical  memory subtests, where lower mean IGF-1 levels were associated with worse performance. Likewise, mean IGF-1 also remained significantly associated with poor performance on the TRAIL  making test, again, a measure of executive function, as well as the controlled word association test, which evaluates language.  Other measures which did not reach statistical significance but were trending are also listed here.  In conclusion, IGF-1 levels have not been well characterized after aneurysmal subarachnoid hemorrhage.  These data suggest that lower plasma IGF-1 levels after hemorrhage are associated with poor performance on multiple tests of memory, executive function, and language 12 months  after ASAH. We acknowledge the limitations of this single-center study evaluating mean IGF-1 scores in a small  sample size, and we also acknowledge that post-discharge plasma samples would be helpful in further evaluating this relationship.  However, we do believe this data provides impetus for our ongoing research examining IGF-1 and other hormones after aneurysmal subarachnoid hemorrhage with the hope of not  only characterizing hormone levels, but also informing interventions aimed at improving long-term outcomes for survivors of aneurysmal subarachnoid hemorrhage.  I thank you for your time, happy to answer any questions either in the chat or by email. Thank you. ♪♪♪

Video Summary

Elizabeth Crago, an assistant professor of nursing at the University of Pittsburgh, presented her research on the association of plasma insulin growth factor (IGF) to memory and cognition after subarachnoid hemorrhage. Subarachnoid hemorrhage is a condition resulting from ruptured cerebral aneurysms and can lead to permanent cognitive deficits. Crago's study found that lower plasma IGF-1 levels after hemorrhage were associated with poor memory, executive function, and language performance 12 months later. This research highlights the potential for interventions to improve long-term outcomes for survivors of subarachnoid hemorrhage.

Asset Subtitle

Neuroscience, Research, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Elizabeth A. Crago

Introduction/Hypothesis: Cognitive impairments often burden survivors of aneurysmal subarachnoid hemorrhage (aSAH). Insulin growth factor (IGF1) is a potent cellular growth-promoting factor with links to memory and cognitive performance and demonstrated independent neuroprotective actions in stroke and neurologic disease. This study sought to examine the relationship between plasma IGF1 levels and cognitive performance in measures of executive function, learning and memory 12 months after aSAH.

Methods: This cohort of 130 aSAH survivors enrolled in an NIH study (NR004339, NR018160) was 54.1 years (SD 10.03) and female (79%) with a mean World Federation Neurological Scale (WFNS) 1.8 (1 = 58.5%; 2 = 20.8). Plasma samples were collected daily 0-14 days after aSAH and banked in a biorepository. Mean plasma IGF1 concentrations were derived from 1221 plasma samples using a commercial sandwich solid-phase ELISA kit. Neuropsychological assessments were evaluated 12 months after aSAH. Descriptives, Spearman correlations and linear regression analyses were completed using SPSS and SAS.

Results: Older age was significantly associated with lower mean plasma IGF1 levels (r = -.418, p<.001). Lower mean IGF1 levels were associated with worse performance in memory measures [Tay copy (r = .215, p=.02); Tay immediate (r =.333, p<.001) and Tay delay recall (r =.318, p<.001)] and working memory sequence (r =.367, p=.04), as well as measures of attention (trails A time r = -.193, p=.03) and mental flexibility (Trails B r = -.25, p=.01). In linear regression models controlling for age and WFNS, mean IGF1 levels remained significantly associated with worse performance on tests of memory (Tay copy p=.02, Tay immediate p=.02, Tay delay p=.002, and working memory sequence p=.05); as well as attention (Trails A p=.02) and language (color word association p=.05).

Conclusions: IGF1 levels have not been well characterized after aSAH. These results suggest lower plasma IGF1 after hemorrhage are associated with poor performance on tests of memory and executive function 12 months after aSAH and provide impetus for future work to further examine these relationships and to inform possible interventions aimed at improving long-term aSAH outcomes.

Meta Tag

Content Type Presentation

Knowledge Area Neuroscience

Knowledge Area Research

Knowledge Level Advanced

Membership Level Select

Tag Subarachnoid Hemorrhage

Tag Outcomes Research

Year 2021

Keywords

Elizabeth Crago

plasma IGF-1 levels

memory

cognition

subarachnoid hemorrhage

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