Swart EL

References (2)

Title : Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease - Baakman_2021_Br.J.Clin.Pharmacol__
Author(s) : Baakman AC , Gavan C , van Doeselaar L , de Kam M , Broekhuizen K , Bajenaru O , Camps L , Swart EL , Kalisvaart K , Schoonenboom N , Lemstra E , Scheltens P , Cohen A , van Gerven J , Groeneveld GJ
Ref : British Journal of Clinical Pharmacology , : , 2021
Abstract : BACKGROUND: Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's Disease (AD) patients, but are associated with multiple side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of a single dose administration of galantamine on CNS functioning in mild to moderate AD patients and its potential to predict long-term treatment response. METHODS: This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their MMSE, NPI and DAD scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. RESULTS: A single dose of galantamine significantly reduced saccadic reaction time (-0.0099; 95%CI=-0.0195,-0.0003; p=.0430), absolute frontal EEG parameters in alpha (-14.9; 95%CI=-21.0,-8.3; p=.0002), beta (-12.6; 95%CI=-19.4,-5.3; p=.0019) and theta (-17.9; 95%CI=-25.0,-10.0; p=.0001) frequencies. Relative frontal (-1.669; 95%CI=-2.999,-0.339; p=.0156) and occipital (-1.856; 95%CI=-3.339,-0.372; p=.0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95%CI=0.158,2.475; p=.0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (-20.4; 95%CI=-31.6,-7.47; p=.0046), beta (-15.7; 95% CI=-28.3,-0.93; p=.0390) and theta (-25.9; 95%CI=-38.4,-10.9; p=.0024) EEG parameters and of relative frontal theta power (-3.27%; 95%CI=-5.96,-0.58; p=.0187) on EEG significantly distinguished responders (n=11) from non-responders (n=32) after 6 months. CONCLUSIONS: This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.
ESTHER : Baakman_2021_Br.J.Clin.Pharmacol__
PubMedSearch : Baakman_2021_Br.J.Clin.Pharmacol__
PubMedID: 34964149

Title : Acetylcholinesterase inhibitors for electroconvulsive therapy-induced cognitive side effects: a systematic review - Henstra_2017_Int.J.Geriatr.Psychiatry_32_522
Author(s) : Henstra MJ , Jansma EP , van der Velde N , Swart EL , Stek ML , Rhebergen D
Ref : Int J Geriatr Psychiatry , 32 :522 , 2017
Abstract : OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for severe late-life depression; however, ECT-induced cognitive side effects frequently occur. The cholinergic system is thought to play an important role in the pathogenesis. We systematically reviewed the evidence for acetylcholinesterase inhibitors (Ache-I) to prevent or reduce ECT-induced cognitive side effects.
METHODS: A systematic search was performed in Pubmed, EMBASE, PsychINFO, and the Cochrane database to identify clinical trials investigating the effect of Ache-I on ECT-induced cognitive side effects. Key search terms included all synonyms for ECT and Ache-I. Risk of bias assessment was conducted by using the Cochrane Collaboration's tool.
RESULTS: Five clinical trials were eligible for inclusion. All studies focused on cognitive functioning as primary endpoint, but assessment of cognitive functioning varied widely in time point of assessment and in cognitive tests that were used. There was also great variety in study medication, route and time of administration and dosages, duration of drug administration, and ECT techniques. Finally, only two out of five studies were considered at low risk of bias. Despite the aforementioned shortcomings, without exception, all studies demonstrated significantly better cognitive performance in individuals treated with Ache-I.
CONCLUSIONS: Despite large heterogeneity in studies, Ache-I appear to have beneficial effects on ECT-induced cognitive side effects, supporting an association with the cholinergic system in ECT-induced cognitive impairment. Methodological sound studies controlling for putative confounders are warranted. Copyright (c) 2017 John Wiley & Sons, Ltd.
ESTHER : Henstra_2017_Int.J.Geriatr.Psychiatry_32_522
PubMedSearch : Henstra_2017_Int.J.Geriatr.Psychiatry_32_522
PubMedID: 28295591