1. HIGH-SENSITIVITY C-REACTIVE PROTEIN (HSCRP) EFFECTS ON COGNITION AND BRAIN HEALTH IN OLDER ADULTS

Abstract

Introduction

Inflammation can affect cognition and brain health in older adults, potentially leading to cognitive decline. Furthermore, systemic inflammatory markers, such as C-reactive protein levels, have been associated with increased risk of cognitive impairment. We aimed to examine the relationship between plasma levels of high-sensitivity C-reactive protein (hsCRP), cognition, and brain regional volume in a large cross-sectional study of older adults. We primarily focused on subcortical brain structures important for learning and memory, including striatal nuclei.

Methods

Participants received neuropsychological testing, provided blood samples, and underwent high-resolution sMRI. Brain volumes were computed using Freesurfer (v. 7.4.1). We used general linear models to examine relationships between plasma hsCRP levels and cognition/regional volumes, with age, sex, ethnicity, study site, intra-cranial volume (for brain volumes) as covariates. Age was treated as a factor with 2 levels (LESS THAN 65 and ≥ 65 years). HsCRP level was log-transformed for analysis. Measures of cognition included short-term memory recall (using the Rey Auditory Verbal Learning Test) and two factors derived from several cognitive measures: “memory” and “fluid IQ” (e.g. executive function). Regional volumes examined included hippocampus, striatum (caudate, putamen, pallidum, accumbens), amygdala, and thalamus.

Results

Data from the Human Connectome Project-Aging study (N=1132; mean age: 61.8 (SD=16), range 36-102 years; 57.2% female) were analyzed. We found that hsCRP levels were negatively associated with the cognitive function, as measured by fluid IQ (p LESS THAN 0.05). We also found that hsCRP levels were negatively associated with brain volume in the following brain regions: hippocampus (p LESS THAN 0.01), acummbens (p LESS THAN 0.01), amygdala (p LESS THAN 0.01), and pallidum (p LESS THAN 0.02).

Conclusions

In our study population, higher plasma hsCRP level correlated with reduction in cognitive function and brain volume. Results from this large sample underscore the importance of inflammation, as measured by hsCRP, as a determinant for brain health. Further longitudinal studies are indicated to assess potential causal relationships.