Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease.

Abstract

Immune dysfunction is important in aging and neurodegeneration; lacking clinically available tools limits research translation. We tested associations of cerebral spinal fluid (CSF) monocyte-to-lymphocyte ratio (MLR)-innate immune activation surrogate-with cognition in an aging and dementia cohort, hypothesizing that elevated MLR is associated with poorer executive functioning. CSF MLR was calculated in well-characterized, genotyped participants enrolled in studies of aging and dementia at University of California, San Francisco Memory and Aging Center (n=199, mean age 57.5 years, SD 11.9). Linear models tested associations with episodic memory and executive function (verbal fluency, speeded set-shifting). Aging was associated with higher CSF monocyte, lower lymphocyte counts, and higher MLRs (p<0.001). MLR was associated with verbal fluency (p<0.05) only. Using clinical labs, we show an inverse association between CSF MLR and executive function in aging and dementia, supporting the utility of clinical labs in capturing associations between innate immune dysfunction and neurodegeneration.