Changes in Regional Cerebral Perfusion after Nicergoline Treatment in Early Alzheimer's Disease: A Pilot Study

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.

Nicergoline improves the depressive behavior of vascular depression in rats by regulating monoamine neurotransmitter receptors expression in hippocampal CA1 region and serum apolipoprotein E4 level / 国际脑血管病杂志

Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.

Efficacy of nicergline combined with hyperbaric oxygen treatment on vascular cognitive impairment / 中华老年医学杂志

Objective To investigate the efficacy of nicergoline combined with hyperbaric oxygen treatment on vascular cognitive impairment.Methods 120 patients with vascular cognitive impairment were randomly divided into 3 treatment groups:nicergoline,hyperbaric oxygen,and both treatment (n=40,each) for 8 weeks.Mini mental state examination (MMSE),Wechsler memory scale (WMS) and activities of daily living scale (ADL) were used as assessing items.The efficacy of treatment in each group was evaluated.Results There were no significant differences in clinical data among the three groups(x2=0.324,t=0.265 and 0.861,P=0.764,0.784 and 0.386).After 8 weeks of intervention,scores of MMSE,WMS and ADL were significantly improved in the combined treatment groups compared with pre-treatment (all P＜0.01),and the improvements were observed in nicergoline group (all P＜0.05),while only MMSE and ADL were improved in hyperbaric oxygen group (both P＜0.05).There were significant differences in scores of MMSE,WMS and ADL between combination therapy group and nicergoline group,hyperbaric oxygen group after treatment (all P＜0.05).But only MMSE had significant difference between niccrgoline group and hyperbaric oxygen group after treatment.No significant side effects were observed in the three groups.Conclusions Combination treatment of nicergline and hyperbaric oxygen has better efficacy on vascular cognitive impairment.It can markedly improve the activities of daily living and cognitive function without significant side effects,which is worthy of application in clinical medicine.

The clinical efficacy of nicergoline combined with donepezil hydrochloride in the treatment of mild vascular dementia and its influence on cognitive function / 中国基层医药

Objective To investigate the clinical efficacy of nicergoline combined with donepezil hydrochlo-ride in the treatment of mild vascular dementia and its influence on cognitive function.Methods 66 patients with mild vascular dementia from neurology were divided into two groups by random numbers,33 cases in each group.On the based of the routine symptomatic treatment,the control group were given nicergoline,the observation group were treated with nicergoline combined with aricept.Four weeks was a course,both groups were continuously treated for 3 courses.Results The MMSE scores of the observation group after treatment was (36.7 ±5.7)points,which was significantly increased compared with before treatment(t =10.137,P <0.05)and the control group(t =11.236,P <0.05);The ADL score was(35.8 ±16.2)points,which was significantly lower compared with before treatment(t =10.825,P <0.05)and the control group(t =11.415,P <0.05);The total effective rate of the observation group was 78.9%,which was higher than 54.5% of the control group(χ2 =9.24,P <0.05).Conclusion Nicergoline com-bined with donepezil hydrochloride in the treatment of mild vascular dementia can significantly improve cognitive func-tion scores,and it is a significant effect,safe and reliable method.

Efficacy of nicergoline on vascular cognitive impairment without dementia / 中华老年医学杂志

Objective To investigate the effect of nicergoline on cognitive ability and executive function for patients with vascular cognitive impairment without dementia (VCIND).Methods Totally 68 patients with VCIND were divided into conventional treatment group (33 cases) and nicergoline treatment group (35 cases,nicergoline 10 mg,tid added on basal conventional treatment).All of cases were continuously treated for 12 weeks.Cognitive ability and executive function before and after treatments were evaluated.Results Test scores of immediate free recall of a list of words,the numbers and symbols transformation,the word fluency,clocks and watches painting,and minimental state examination (MMSE) were significantly higher in nicergoline treatment group than in conventional treatment group (P＜0.05).Conclusions Nicergoline may improve attention and memory as well as cognitive ability in patients with vascular cognitive impairment without dementia.

Clinical analysis of nicergoline in treatment for 80 patients with chronic cerebral circulation insufficiency / 局解手术学杂志

Objective To observe the curative effect of nicergoline in the treatment of chronic cerebral circulation insufficiency ( CC-CI) . Methods 160 cases with CCCI were randomly divided into the treatment group which were administered 10 mg of oral Nicergoline, three times per day for one month,and the control group which were given 20 mg of oral nimodipine,three times per day for one month. The clinical effective rate and the transcranial Doppler ultrasound ( TCD) between the two groups before and after treatment were observed. Results There were significant difference in clinical effective rate and TCD index assessment between the two groups(P<0. 05). Conclu-sion Nicergoline is an effective and safe treatment for chronic cerebral circulation insufficiency.

Clinical study of nicergoline and aniracetam in treatment of mild and moderate cognitive dysfunction after cerebral infarction / 重庆医学

Objective To observe the clinical efficacy and safety of nicergoline and aniracetam in treatment of mild and moderate cognitive dysfunction after cerebral infarction .Methods Infarction were enrolled after 70 cases of mild and moderate cognitive im-pairment patients were randomly divided into nicergoline treatment group (observation group) and aniracetam treatment group(con-trol group) ,all 35 cases .After 12 weeks of treatment were compared before and after treatment mini mental state examination (MMSE) ,activities of daily living scale(ADL) scores and transcranial Doppler(TCD) to improve the situation .Results After 12 weeks ,both groups after treatment compared with treatment MMSE score was significantly higher (P< 0 .05) ,and nicergoline group than aniracetam group(P< 0 .01);ADL score before treatment were significantly reduced (P< 0 .05) ,TCD improvement nicergoline group than aniracetam group (P<0 .01) .Conclusion Nicergoline mild and moderate cognitive dysfunction after cerebral in-farction have significant effects ,and better than aniracetam ,no significant adverse reactions occur for a wide range of clinical applications .

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies / 药物分析学报

A fast,simple and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL,a main metabolite of nicergoline) in human plasma.One-step liquid-liquid extraction (LLE) with diethyl ether was employed as the sample preparation method.Tizanidine hydrochloride was selected as the internal standard (IS).Analysis was carried out on a Diamonsil ODS column (150 mm × 4.6 mm,5 μm) using acetonitrile-ammonium acetate (0.1 mol/L) (15/85,v/v) as mobile phase at detection wavelength of 224 nm.The calibration curves were linear over the range of 2.288-73.2 ng/mL with a lower limit of quantitation (LLOQ) of 2.288 ng/mL.The intra- and inter-day precision values were below 13％ and the recoveries were from 74.47％ to 83.20％ at three qtality control levels.The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers.

Nicergoline in treatment of vascular dementia: a consecutive,multicenter,double-blind clinical trial / 中华神经科杂志

Objective To test the efficacy and safety of nicergoline in treatment of vascular dementia patients with mild or moderate cognitive impairment. Methods A multicenter,double blind,randomized,efficient drug controlled clinical trial was carried out All the subjects met the DSM-Ⅲ criteria for vascular dementia We used MMSE and WMS as main assessing items and ADL,CGI as secondary assessing items. Results 103 subjects were assessed MMSE were raised in both groups after the treatment and more obvious in nicergoline group than in anecetan group (1 62?2 33 and 2 88?2 85 respectively) WMS raised in nicergoline group (5 04?10 61),but not in anecetan group (1 98?9 49) ADL and CGI (SI) showed decreased scores in both groups Total efficiency of nicergoline was 80 0% and of anecetan was 56 6%. Conclusions Nicergoline was an effective drug in treatment of vascular dementia and more effective than anecetan Using nicergoline 60 mg per day was safe

The effect of nicergoline on cognitive dysfunction in the severe traumatic brain injury / 中国康复理论与实践

@#Objective:To explore the therapeutic effect and mechanism of nicergoline on the severe traumatic brain injury. Methods:52 TBI patients were divided into the routine treatment group and nicergoline treatment group. Before and after rehabilitation treatment the SPECT and cognitive function were assessed. Results:The lesions were both decreased in nicergoline group and routine group in SPECT scanning, but there was no difference in statistics. The value of cognitive function of the nicergoline treatment group, especially function-oriented and memory, was higher than that of the routine treatment group(P<0.05).Conclusions:The nicergoline can improve cognitive function of the severe traumatic brain injury.