Biomarkers of inflammation and brain damage seven years post-stroke

Introduction

Biomarkers of inflammation and brain damage are associated with neurodegeneration and dementia but are scarcely investigated post-stroke. We hypothesized that biomarkers of brain tissue damage and inflammation are associated with i) cognition and imaging markers of brain pathology seven years post-stroke and ii) long-term cognitive deterioration post-stroke.

Methods

All patients with a first-ever stroke or TIA admitted to the stroke unit, Bærum Hospital, Norway, during 2007/2008 were invited to participate in the CAST (Cognition After Stroke) study and invited to a follow-up after one and seven years with cognitive assessments and diagnoses of dementia, mild cognitive impairment (MCI) or normal. After seven years, we measured serum glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), Interleukin (IL) 8, 12, 18, and high sensitive C-reactive protein (hsCRP) and brain MRI for assessment of Fazekas and global cortical and medial temporal lobe atrophy (MTA).

Results

Of 227 subjects recruited, 116 completed the seven-year follow-up, 113 with blood biomarkers, and were included in this study. Of these, 77 had complete MRI examinations. Mean age at baseline was 67.9 (SD 11.0) years, 87 (77 %) suffered an ischemic stroke, and 52 (46%) were women. The mean age after seven years was 75.4 (SD 11.1). At one- and seven-years follow-up, 62 (55%) and 45 (40%) had normal cognition, 37 (33%) and 42 (37 %) MCI, while 14 (12 %) and 26 (23%) had dementia, respectively. Cognitively, 35 patients progressed during follow-up. In unadjusted logistic regression, only hsCRP was associated with post-stroke dementia (odds ratio 1.08, 95% confidence interval 1.02 to 1.14, p=0.01). Adjusting for age did not change the result (OR 1.09, 95% confidence interval 1.06-1.19, p<0.001). In univariate ordinal regression, only NSE was associated MTA, but not after age adjustment. None of the biomarkers was associated with deterioration of cognition from one to seven years post-stroke.

Discussion

In this exploratory study, only elevated levels of hsCRP were associated with dementia seven years post-stroke, indicating a role of neuroinflammation in the development of cognitive impairment in long-term follow-up. [Clinicaltrials.gov (NCT00506818)]