ArticleAnnals of neurology2021
α4β2
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Falls Induced by Optogenetic Inhibition of Basal Forebrain Cholinergic Projections after Dorsomedial Striatal Dopamine Depletion in a Dual Disruption Model of Falling Vulnerability in Parkinson Disease.bioRxiv : the preprint server for biology · 2026Article
- Do we need drugs for psychiatric symptoms specifically for Parkinson's disease?Journal of Parkinson's disease · 2026Review
- How to advance the pharmacological management of cognitive impairment in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Varenicline-mediated cholinergic activation through α4β2 nAChR inhibits microglial neuroinflammation and alleviates neuropathic pain and depression following spinal cord injury.Journal of translational medicine · 2026Article
- The central cholinergic system as a therapeutic target in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Cholinergic System Changes in Dopa-Unresponsive Freezing of Gait in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Enantiospecific Positive Allosteric Modulation of α4β2 Nicotinic Receptor Subtypes.ACS chemical neuroscience · 2025Article
- Cortical α4β2-nicotinic acetylcholine receptors and cognitive decline in Parkinson's disease.Journal of Parkinson's disease · 2025Article
- Article
- Cortico-striatal action control inherent of opponent cognitive-motivational styles.bioRxiv : the preprint server for biology · 2024Article
- Alterations in Neuronal Nicotinic Acetylcholine Receptors in the Pathogenesis of Various Cognitive Impairments.CNS neuroscience & therapeutics · 2024Review
- The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.Neurology · 2024Article
- The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.Current neuropharmacology · 2024Review
- Clinical trials for cognition in Parkinson's disease: Where are we and how can we do better?Parkinsonism & related disorders · 2023Review
- Design issues in crossover trials involving patients with Parkinson's disease.Frontiers in neurology · 2023Article
- Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches.The Lancet. Neurology · 2022Review
- Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease.Progress in brain research · 2022Review
- Evolution characteristics of dynamic balance disorder over the course of PD and relationship with dopamine depletion.Frontiers in aging neuroscience · 2022Article
- The Cholinergic Brain in Parkinson's Disease.Movement disorders clinical practice · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAttentional deficits following degeneration of brain cholinergic systems contribute to gait-balance deficits in Parkinson disease (PD). As a step toward assessing whether α4β2* nicotinic acetylcholine receptor (nAChR) stimulation improves gait-balance function, we assessed target engagement of the α4β2* nAChR partial agonist varenicline.
methodsNondemented PD participants with cholinergic deficits were identified with [
resultsVarenicline doses (0.25mg per day, 0.25mg twice daily [b.i.d.], 0.5mg b.i.d., and 1.0mg b.i.d.) produced 60 to 70% receptor occupancy. We selected 0.5mg orally b.i.d for the crossover study. Thirty-three participants completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved sustained attention test performance. We obtained identical conclusions in 28 participants with treatment compliance confirmed by plasma varenicline measurements.
interpretationVarenicline occupied α4β2* nicotinic acetylcholine receptors, was tolerated well, enhanced attention, and altered gait performance. These results are consistent with target engagement. α4β2* agonists may be worth further evaluation for mitigation of gait and balance disorders in PD. ANN NEUROL 2021;90:130-142.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.