The use of rotigotine as a drug to improve cognitive function in individuals with Alzheimer’s disease
Alzheimer’s disease (AD) is a progressive brain disorder that causes a degeneration of memory and cognitive skills majorly caused by two primary cardinal lesions: neurofibrillary tangle and the senile plaque.1 However recently, new evidence has emerged that impairment of dopaminergic transmission can contribute to cognitive dysfunction in AD.2 Dopamine is associated with memory as midbrain dopamine neurones project directly to the hippocampus and thus to the surrounding mediotemporal lobe. Animal studies have demonstrated that dopamine is an imperative precursor for hippocampal synapses for both prime cellular memory and long-term memory.3 This is concordant with the mechanism by which dopamine agonists can enhance cholinergic transmission and cortical plasticity in the early stages of AD.2
A study published in JAMA Network Open assessed the efficacy of a specific dopamine antagonist, rotigotine, in patients with mild-to-moderate AD. This Phase II monocentric, double-blind, placebo-controlled study included 94 patients randomized to receive either a rotigotine 2mg transdermal patch for 1 week then a 4mg patch for 23 weeks or placebo. To assess efficacy, patients underwent a series of tests such as Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11), Frontal Assessment battery (FAB) and Alzheimer’s Disease Cooperative Study- Activities of Daily Living (ADCS-ADL). ADAS-Cog-11 was used as a primary endpoint whilst both ADCS-ADL and FAB were used as a secondary endpoint.2
The estimated mean average in ADAS-Cog-11 was 2.95 [95% CI, 2.51 to 3.33] in the rotigotine and 2.66 for the control group [95% CI, 2.31 to 3.01; p value of 0.82] showing no significant difference between the two groups. However, secondary outcomes showed a higher degree of significant difference in FAB (p value of 0.02) and ADCS-ADL (p value of 0.04) scores.2
Mean change in FAB score was 0.48 [95% CI, 0.31 to 0.65] for the rotigotine group and -0.66 [95% CI, -0.80 to -0.52] for the placebo group. Additionally, the mean change in ADCS-ADL score was -3.32 [95% CI, -4.02 to -2.62] for the rotigotine group and -7.24 [95% CI, -7.84 to -6.64] for the placebo group which can further confirm the potential efficacy of the drug as there was a much larger disparity of score in the rotigotine group.2 These results indicate a potential enhancement in frontal lobe functions for the rotigotine group compared with the placebo.
These findings can suggest that rotigotine could aid the improvement of cognitive functions associated with the frontal lobe in individuals. Furthermore, it was also concluded that rotigotine can increase prefrontal cortex activity shown through a larger range of oscillatory activity in alpha and beta frequencies in EEG response to TMS.2
Written by Zoe Barley
- DeTure M, Dickson, D. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(32)
- Koch G et al. Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease: A Randomised Clinical Trial.JAMA Neu. 2020Jul;3(7).
- Pan X et al. Dopamine and Dopamine Receptors in Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis.Front Ageing Neurosci. 2019Jul;11(175).