Title:
Cerebral microbleeds and long-term cognitive outcome: longitudinal cohort study of stroke clinic patients.

Abstract:
Vascular cognitive impairment causes significant disability in the elderly and is common following ischaemic stroke. Although the underlying mechanisms and prognostic factors remain unclear, small vessel diseases are known to contribute. Cerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI) manifestation of small vessel diseases and may contribute to vascular cognitive impairment, particularly frontal-executive functions. We hypothesized that baseline CMBs would predict long-term cognitive outcome, specifically frontal-executive function.
A cohort of consecutive patients found to have CMBs when first referred to a stroke clinic, together with a CMB-free control group matched for age, gender and clinicoradiological characteristics, were invited for follow-up cognitive assessment a median of 5.7 years later. MRI and detailed cognitive assessment (including current intellectual function, verbal memory, visual memory, naming skills, perceptual functions, frontal-executive functions; and speed and attention) were performed at baseline and follow-up. Patients were classified (blinded to MRI and clinical data) as impaired or unimpaired in each domain using predefined criteria. We compared the prevalence of cognitive impairments in each domain at baseline and follow-up and investigated clinical and radiological predictors [including baseline CMBs and white matter changes (WMCs)] of frontal-executive cognitive impairment.
Of the original cohort of 55 patients, 13 died without follow-up. Twenty-six of the surviving patients (9 with, 17 without baseline CMBs) agreed to follow-up neuropsychological assessment; 21 of these patients had a repeat MRI scan. The median number of cognitive domains impaired increased, regardless of the presence of baseline CMBs (with baseline CMBs: median 3, range 0-5 at follow-up vs. median 2, range 0-2 at baseline, p = 0.016; without CMBs: median 1.0, range 0-5 at follow-up vs. median 0, range 0-5 at baseline, p = 0.035). Frontal-executive impairment at follow-up was more prevalent in patients with baseline CMBs than in those without (78 vs. 29%, p = 0.038). The presence of baseline CMBs predicted frontal-executive impairment at follow-up (OR 8.40, 95% CI 1.27-55.39, p = 0.027). Fifty percent of patients with CMBs versus 8% of patients without baseline CMBs developed new CMBs (p = 0.047). The severity of WMCs increased; the difference was statistically significant only in patients without baseline CMBs (p = 0.027). There were no new cortical infarcts.
In stroke clinic patients, CMBs are consistently associated with frontal-executive impairment; baseline CMBs are associated with frontal-executive impairment at follow-up after 5.7 years. The presence of CMBs has prognostic relevance for long-term cognitive outcome in stroke clinic patients, and may help to optimally target preventive strategies in individuals at highest risk of cognitive decline.