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Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl\u20103\u2010n\u2010butylphthalide (NBP) is effective for cognitive impairment of vascular origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomized, double\u2010blind, placebo\u2010controlled trial, we enrolled patients aged 50\u201370\u00a0years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating \u22650.5 on at least one domain and global score \u22640.5; a mini\u2010mental state examination score \u226520 (primary school) or \u226524 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned to NBP 200\u00a0mg three times daily or matched placebo (1:1) for 24\u00a0weeks according to a computer\u2010generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale\u2010cognitive subscale (ADAS\u2010cog) and clinician's interview\u2010based impression of change plus caregiver input (CIBIC\u2010plus) after 24\u00a0weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention\u2010to\u2010treat (ITT) population and the per protocol population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS\u2010cog (NBP change \u22122.46 vs. placebo \u22121.39; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.03; ITT) and CIBIC\u2010plus (80 [57.1%] vs. 59 [42.1%] patients improved; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.01; ITT). NBP\u2010related AE were uncommon and primarily consisted of mild gastrointestinal symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Over the 6\u2010month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2015.04.010","type":"journal-article","created":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T19:20:38Z","timestamp":1434396038000},"page":"89-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["The effects of DL\u20103\u2010n\u2010butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double\u2010blind, placebo\u2010controlled 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