Nimodipine is a dihydropyridinic calcium antagonist that quickly and easily crosses the BBB and reaches a high concentration in cerebrospinal fluid (CSF). It improves cerebral perfusion after acute ischemia
 and reduces neurological deficits
[27–29]. It has specific affinity for receptor operated calcium channels in cerebral vessels and for specific membrane-located receptor sites that may be associated with the pharmacological action of nimodipine in the brain
[30, 31]. Results from in vivo research showed that nimodipine also has a high affinity for specific binding sites in the cortex, the dentate gyrus and the hippocampus, which are known to be the core regions involved in cognitive function
. Based on this evidence, many studies have tried to elucidate the role of nimodipine in treating cognitive impairment. A published Meta-analysis from 14 randomized, double-blind and control clinical trials (3166 cases) suggested that nimodipine (90 mg/d, 12–26 weeks) could improve the cognitive deficits caused by unclassified disease, Alzheimer’s disease, cerebrovascular disease, or mixed Alzheimer’s and cerebrovascular disease
. A wide variety of scales, such as the mini-mental state examination (MMSE), short cognitive performance test (SKT), clinical global impression (CGI), Sandoz clinical assessment geriatric scale (SCAG) and Alzheimer’s disease assessment score-cognitive component (ADAS-cog), were adopted to evaluate cognitive impairment in this Meta-analysis. The results suggested that nimodipine could significantly delay the decrease in SCAG score [WMD (weighted mean difference) -11.75, 95% CI −15.64–-7.85, P < 0.00001] and CGI (WMD −1.31, 95% CI −1.73–-0.89, P <0.00001) at 12 weeks following stroke
The first randomized, double-blind, controlled trial focusing on subcortical vascular dementia and multiple infarction dementia presented the results in 2005
. This study noted a 22.4% reduction in deterioration (3 or more point-drop versus baseline) on the MMSE within a 52-week period in nimodipine-treated patients when compared with the placebo group, who had similar demographic characteristics. There was also a significant delay in the deterioration of SCAG scores and significant improvement in SCAG scores.
The pivotal principal of cognitive impairment prevention following stroke is to intervene early rather than cure late. An important study in Hong Kong (China) was carried out to examine the effectiveness of nimodipine prevention/therapy on cognitive impairment in acute cerebral infarction patients, with the aim of demonstrating the effectiveness of early intervention after stroke
. Although this study was a single-blind randomized controlled trial and enrolled 100 patients, promising results were found in acute cerebral infarction patients. In the intervention patients, Fuld object-memory evaluation (FOME) mean scores were significantly improved and the death rate did not increase within a 12-week period.
An important consideration is at which time-point intervention with nimodipine should occur. This varies between studies, as most are administered at a chronic stage (i.e. >6 months after the stroke) and 2 weeks after the stroke
[22, 35]. However, a series of chain reactions induce a large amount of neuronal damage at acute and subacute stages of stroke
. Theoretically, nimodipine could have clinical benefits due to its ability to modulate blood vessels and protect neurons, especially its probable ability to regulate the capillary with relatively intact structure and functions in the severely injured brain
[27, 30, 37, 38]. It is thus conceivable that it is clinically beneficial to begin nimodipine therapy at early stage after the stroke.
The aim of this study is therefore to evaluate the clinical efficacy and safety of nimodipine, administered within seven days after an acute ischemic stroke, in the prevention of mild cognitive impairment.