SHM Student and Resident Research Grant: The Effect of Anemia on Cognitive Function During Hospitalization

The Effect of Anemia on Cognitive Function During Hospitalization
Author: Stephanie Cardenas, Medical Student, University of Chicago Pritzker School of Medicine Faculty
Mentor: Dr. Micah Prochaska, MD, Assistant Professor of Medicine, University of Chicago Medicine
SHM Mentor: Allison Ashford, MD, Assistant Professor, University of Nebraska Medical Center

Project-specific aims:
This past summer, I learned how anemia can contribute to cognitive function in hospitalized patients. Since previous studies have shown that in the outpatient setting anemia is associated with cognitive impairment (1,2), we wanted to test this association in the inpatient setting. Understanding this association is important because the hemoglobin (Hb) levels tolerated in hospitalized patients (7-8g/dL) as a result of restrictive red blood cell (RBC) transfusion practices are lower than the Hb levels associated with cognitive impairment in the outpatient setting (3). As a result, hospitalized patients with anemia may have significant cognitive effects from the low Hb levels of anemia. Therefore, our specific aims were to collect prospective data on hospitalized patients with anemia, and to determine whether Hb level is associated with cognitive function and cognitive fatigability.

Project design:
This prospective observational study included hospitalized general medicine patients (≥18 years old) with anemia (Hb <10g/dL) at the University of Chicago Medical Center. Patients answered survey questions that measured cognitive fatigability and cognitive impairment. Cognitive fatigability, a self-reported measure of cognitive fatigue related to physical activity, was measured by the Pittsburgh Fatigability Scale (PFS). Higher scores indicate higher fatigability and therefore more fatigue at any given level of activity. Cognitive impairment was measured using the Short Portable Mental Status Questionnaire (SPMSQ), a 10-item questionnaire that detects the presence of intellectual impairment with more errors suggesting a higher degree impairment. Lastly, Hb levels, patient demographics, and other clinical data were collected through hospital administrative data. Statistical analysis was performed using Stata statistical software. Patients with gastrointestinal bleeding and dementia were excluded from the analysis. Multivariable linear regression models in a stepwise fashion were used to test the association between a patient’s nadir Hb level and their cognitive fatigability or cognitive impairment.

Preliminary results:
We had 759 patients included in our analysis. In the adjusted regression analysis, our first model showed an increase in baseline cognitive fatigability with Hb levels between 8.0-8.9 g/dL (β=2.5; p=0.05) and a larger increase in baseline cognitive fatigability with Hb levels less than 7.0 g/dL (β=3.1; p=0.02) (Table 3). In model 2 we had a similar but larger effect of increased cognitive fatigability with Hb between 8.0-8.9 g/dL (β=2.5; p=0.05) and less than 7.0 g/dL (β=3.7; p=0.01). In model 3 there was increased cognitive fatigability with Hb less than 7.0 g/dL (β=3.7; P=0.01). It also showed increased cognitive fatigability with the Hb between 8.0-8.9 g/dL (β=2.3; p=0.07), but that effect was not statistically significant. Model 4 showed no association between SPMSQ scores and Hb levels. Model 5 showed an increase in cognitive fatigability with Hb levels less than 7.0 g/dL (β=2.9; p=0.03), but no association for Hb levels between 8.0-8.9 g/dL (β=1.6; p=0.21). In all of the models, there was no association between baseline cognitive fatigability and Hb levels between 7.0-7.9 g/dL (Table 1).

Significance of results:
These data suggest that in hospitalized patients with anemia, lower Hb levels are associated with higher baseline cognitive fatigability. These results also suggest that anemia negatively affects cognition in the inpatient setting and is worse at lower Hb levels. In addition, we saw a similar outcome that was statistically significant of lower Hb levels (below 7 g/dL) associated with higher cognitive fatigability in patients with no cognitive impairment. This result suggests that even if a patient has no cognitive impairment measurable by current standardized tools (SPMSQ), anemia may be either a risk factor for or harbinger of future mental cognitive decline due. These findings highlight the limitations of and potential consequences of universal restrictive transfusion practices, which may not be optimal for all patients and have effects on their overall cognitive function. Our work also raises the possibility that there could be a cognitive benefit of keeping patients' Hb levels during hospitalization higher through transfusion of RBCs at more liberal or higher Hb thresholds.
In the future, we plan to increase our patient population as well as further study the short term and long term effects of Hb levels on cognitive function.

References:

1. Lucca U, Tettamanti M, Mosconi P, et al. Association of Mild Anemia with Cognitive, Functional, Mood and Quality of Life Outcomes in the Elderly: The “Health and Anemia” Study. PLOS ONE. 2008;3(4):e1920. doi:10.1371/journal.pone.0001920
2. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006;119(4):327-334.
3. Carson JL, Guyatt G, Heddle NM, et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316(19):2025-2035. doi:10.1001/jama.2016.9185