Infection, inflammation and post-stroke cognitive impairment

Abstract

Background Infection and inflammation are risk factors for dementia in population-based cohorts, however studies in stroke are scarce. We determined the prevalence of stroke-associated infection and routinely measured inflammatory biomarkers during hospitalization for stroke, and their associations with global and domain-specific cognition acutely and at 6-months. Methods A prospective stroke cohort completed the Oxford Cognitive Screen ≤2 weeks and at 6 months. Global post-stroke cognitive impairment (PSCI) was defined as proportion of domains impaired and domain-specific impairment was binarized as present/absent. Infection, inflammatory markers (C-reactive protein-CRP, white cell count-WCC, and neutrophil/lymphocyte ratio-NLR), and systemic inflammatory response syndrome-SIRS, were ascertained throughout admission through linkage to electronic patient records-EPRs supplemented by hand-searches. Associations of infection, inflammatory markers, and SIRS, with acute and 6-month global and domain-specific cognitive impairment were analyzed using multivariable regression adjusting for demographic/vascular factors and stroke severity. Results Among 255 patients (mean/SD age=73.9/12.6 years, 46.3% female, mean/SD education=12.6/3.7 years, median NIHSS=5, range 0-30), infection was present in 90 (35.3%) patients at mean/SD 4.4/6.9 days post-stroke, most commonly pneumonia (47/90, 52%) and urinary tract infection (39/90, 43%). Admission WCC was elevated in 64 (25.1%, mean/SD=9.5/3.2x109/L), CRP in 105 (41.2%, mean/SD=27.5/50.9 mg/L), NLR in 97 (55.7%, mean/SD=5.5/4.5) and SIRS in 53 (26.6% with 45.2% positive overall during admission). Infection was associated with acute and 6-month PSCI (p<0.05adj) with stronger associations acutely for severe infection (infection+SIRS,p=0.02adj). Acute impairments in language, executive function and attention domains and 6-month impairment in number processing (allp<0.05adj) were associated with infection. No significant relationships were found for any biomarker and cognitive impairment. Conclusion Infection and elevations in routinely measured inflammatory biomarkers are common after stroke, however only infection is a risk factor for PSCI, suggesting that the rise in these biomarkers may be non-specific. Infection may present a tractable target for reducing PSCI.