Nicergoline in senile dementia of alzheimer type and multi-infarct dementia: a double-blind, placebo-controlled, clinical and EEG/ERP mapping study

Abstract

In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multiinfarct dementia (MID), based on computed tomography and Hachinski scores (< or = 49 SDAT, > or = 7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC. SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable-the Clinical Global Impression (CGI)-a significant superiority of Global Impression (CGI)-a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (chi 2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (chi 2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.

Is It Possible to Treat Vascular Dementia?

“…However, it is very difficult to draw any firm conclusions in the absence of randomized placebo-controlled studies of large populations. In a double-blind, placebo-controlled study [21], 112 patients were treated with nicergoline, a thrombolytic, vasoactive ergot alkaloid. Nicergoline improved vigilance and information processing in the neuropsychological assessment of patients with degenerative and vascular dementia.…”

Electrical Sources of P300 Event-Related Brain Potentials Revealed by Low Resolution Electromagnetic Tomography

“…In mildly demented patients, the centroparietal P300 amplitude increased after one treatment intravenously with 0.2 g amantadine sulfate [11] and in mildly to moderately demented patients with probable dementia of Alzheimer's type and with multi-infarct dementia, P300 latency was shortened after 8 weeks' treatment with 2 ! 30 mg nicergoline [12]. Moreover, the shortening of P300 latency and the improvement of the cognitive dysfunction were significantly correlated [13].…”

Drugs and Vascular Dementia

“…The best-studied ergot rye derivative is the ergoloid mesylate Hydergine ® ; a review of 151 studies showed that it induces a modest improvement in cognition, daily activities and behavior [30]. Nicergoline (Sermion ® ), as observed in a small number of studies, improves cognition, vigilance and the EEG trace, both in AD and VaD [31][32][33]. The combination of almitrine and raubasine (Duxil ® ), reviewed by Allain and Bentué-Ferrer [34], improves many cognitive parameters as well as the neurosensory symptoms of ischemia/hypoxia (e.g.…”