Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

OBJECTIVE: To determine the occurrence of acute cerebral microinfarcts (ACMIs) in memory clinic patients and relate their presence to vascular risk and cognitive profile, CSF and neuroimaging markers, and clinical outcome. METHODS: The TRACE-VCI study is a memory clinic cohort of patients with vascular brain injury on MRI (i.e., possible vascular cognitive impairment [VCI]). We included 783 patients (mean age 67.6 ± 8.5, 46% female) with available 3T diffusion-weighted imaging (DWI). ACMIs were defined as supratentorial DWI hyperintensities <5 mm with a corresponding hypo/isointense apparent diffusion coefficient signal and iso/hyperintense T2*-weighted signal. RESULTS: A total of 23 ACMIs were found in 16 of the 783 patients (2.0%). Patients with ACMIs did not differ in vascular risk or cognitive profile, but were more often diagnosed with vascular dementia (odds ratio [OR] 5.1; 95% confidence interval [CI] 1.4-18.9, p = 0.014). ACMI presence was associated with lower levels of β-amyloid (p < 0.004) and with vascular imaging markers (lacunar infarcts: OR 3.5, CI 1.3-9.6, p = 0.015; nonlacunar infarcts: OR 4.1, CI 1.4-12.5, p = 0.012; severe white matter hyperintensities: OR 4.8, CI 1.7-13.8, p = 0.004; microbleeds: OR 18.9, CI 2.5-144.0, p = 0.0001). After a median follow-up of 2.1 years, the risk of poor clinical outcome (composite of marked cognitive decline, major vascular event, death, and institutionalization) was increased among patients with ACMIs (hazard ratio 3.0; 1.4-6.0, p = 0.005). CONCLUSION: In patients with possible VCI, ACMI presence was associated with a high burden of cerebrovascular disease of both small and large vessel etiology and poor clinical outcome. ACMIs may thus be a novel marker of active vascular brain injury in these patients.