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Related Concept Videos

Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
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Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

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Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
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Direct-Acting Cholinergic Agonists: Pharmacokinetics01:31

Direct-Acting Cholinergic Agonists: Pharmacokinetics

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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

Direct-Acting Cholinergic Agonists: Therapeutic Uses

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
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Myasthenia Gravis: Diagnostic Tests01:15

Myasthenia Gravis: Diagnostic Tests

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Myasthenia gravis is an autoimmune condition affecting neuromuscular transmission, causing generalized weakness in skeletal muscles. Initial diagnoses rely on patients' signs, symptoms, and medical history. The challenge lies in distinguishing myasthenia from other muscular dystrophies. An important diagnostic feature is the significant improvement of symptoms after administering anticholinesterase inhibitors.
The edrophonium test is a diagnostic tool for myasthenia gravis. It involves...
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Cholinergic Neurons: Neurotransmission01:23

Cholinergic Neurons: Neurotransmission

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Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
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Related Experiment Video

Updated: Sep 16, 2025

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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Association of a Brief Computerized Cognitive Assessment With Cholinergic Neurotransmission: Assessment Validation

Mouna Attarha1, Ana De Figueiredo Pelegrino2, Lydia Ouellet2

  • 1Posit Science Corporation, 160 Pine St Suite 200, San Francisco, CA, 94111, United States, 1 267-930-4000.

JMIR Formative Research
|July 7, 2025
PubMed
Summary

A new computerized cognitive assessment shows association with brain health markers, specifically cholinergic neurotransmission. This accessible tool offers efficient cognitive screening for early detection of decline in older adults.

Keywords:
FEOBV-PETPETVAChT[18F]fluoroethoxybenzovesamicolacetylcholineanterior cingulateassessment accessibilityassessment validation studybrain healthcholinergic functioncholinergic neurotransmissioncognitive statuscomputerized cognitive assessmentneurotransmissionolder personpositron emission tomographyretrospective analysisself-administeredvesicular acetylcholine transporterweb-based cognitive assessment

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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Medical Imaging

Background:

  • Computerized cognitive assessments often lack validation against biological brain health indicators.
  • Existing validation typically relies on traditional neuropsychological measures.
  • Need for objective biological validation of digital cognitive tools.

Purpose of the Study:

  • To evaluate the association between a self-administered computerized cognitive assessment and cholinergic neurotransmission.
  • To validate the Double Decision cognitive assessment against biological markers using [18F]fluoroethoxybenzovesamicol (FEOBV) positron emission tomography (PET).
  • To assess concurrent validity with established neuropsychological tests in healthy older adults.

Main Methods:

  • Retrospective analysis of baseline data from the INHANCE trial.
  • Used FEOBV-PET to measure tracer binding in the anterior cingulate cortex.
  • Examined the association between the Double Decision assessment and FEOBV binding, and neuropsychological performance.

Main Results:

  • The Double Decision assessment was significantly associated with FEOBV binding in the anterior cingulate cortex, explaining 8% of the variance.
  • The assessment demonstrated concurrent validity with neuropsychological measures of executive function and global cognition.
  • The tool was sensitive to age, usable, and completed in an average of 3 minutes.

Conclusions:

  • This study presents the first brief, self-administered computerized cognitive assessment linked to cholinergic network health.
  • The tool is scalable, accessible via internet devices, and offers a cost-efficient cognitive screening method.
  • Findings support its potential for early cognitive decline detection and broad clinical/non-clinical applications.