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Baakman AC, Gavan C, van Doeselaar L, et al. Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease. Br J Clin Pharmacol. 2021;doi: 10.1111/bcp.15206.
Baakman, A. C., Gavan, C., van Doeselaar, L., de Kam, M., Broekhuizen, K., Bajenaru, O., Camps, L., Swart, E. L., Kalisvaart, K., Schoonenboom, N., Lemstra, E., Scheltens, P., Cohen, A., van Gerven, J., & Groeneveld, G. J. (2021). Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease. British journal of clinical pharmacology, . https://doi.org/10.1111/bcp.15206
Baakman, Anne Catrien, et al. "Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease." British journal of clinical pharmacology vol. (2021). doi: https://doi.org/10.1111/bcp.15206
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. Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease. Br J Clin Pharmacol. 2021 Dec 28; doi: 10.1111/bcp.15206. Epub 2021 Dec 28. PMID: 34964149.
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Br J Clin Pharmacol. 2021 Dec 28; doi: 10.1111/bcp.15206. Epub 2021 Dec 28.

Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease.

British journal of clinical pharmacology

Anne Catrien Baakman, Carmen Gavan, Lotte van Doeselaar, Marieke de Kam, Karen Broekhuizen, Ovidiu Bajenaru, Laura Camps, Eleonora L Swart, Kees Kalisvaart, Niki Schoonenboom, Evelien Lemstra, Philip Scheltens, Adam Cohen, Joop van Gerven, Geert Jan Groeneveld

Affiliations

  1. Centre for Human Drug Research, CL, Leiden, The Netherlands.
  2. Clinicii de neurologie a Spitalului Universitar de Urgenta, Bucharest, Romania.
  3. Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, HV, Amsterdam, The Netherlands.
  4. Department of Neurology, Spaarne Gasthuis, Haarlem, The Netherlands.
  5. Alzheimer Center Amsterdam, Amsterdam UMC, HZ, Amsterdam, The Netherlands.

PMID: 34964149 DOI: 10.1111/bcp.15206

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.

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Keywords: Alzheimer’s disease; cholinergic challenge; galantamine; pharmacology

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