Cognitive Testing for Episodic Memory

Overseen By Ilaina Edelstein

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Not undergoing brain monitoring, Age, Cognitive impairment

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how certain brain areas, specifically the posterior cingulate cortex (PCC), assist with memory and decision-making. Participants will engage in various computer-based tasks (cognitive testing) while researchers record their brain activity to determine how different brain parts contribute to memory and decision-making. This research could illuminate memory issues common in conditions like Alzheimer's and schizophrenia. The trial seeks individuals already undergoing brain monitoring for epilepsy, though it does not focus on epilepsy itself. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance understanding of memory-related conditions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this cognitive testing is safe?

Research shows that cognitive tests, like those used in this study, are generally safe for participants. These tests help researchers understand how well people think and remember. They have been thoroughly studied and are known to be reliable and accurate.

In simple terms, these tests effectively measure their intended outcomes without causing harm. In this study, participants will make decisions and answer questions while researchers record their brain activity. This recording resembles the routine monitoring done for some epilepsy patients.

Since other medical settings already use these methods, researchers are confident in their safety. The study does not involve new drugs or invasive treatments, which usually means fewer side effects. Participants will only perform tasks on a computer, making this a very low-risk approach. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different types of cognitive tasks affect brain activity, which could deepen our understanding of memory and decision-making processes. Unlike traditional treatments for memory issues that might involve medications or general cognitive exercises, these tasks specifically target episodic memory and executive function. By recording brain activity in key areas like the posterior cingulate cortex, hippocampus, and prefrontal cortex, researchers hope to uncover precise mechanisms that differentiate between types of memory and decision-making. This could lead to more targeted and effective interventions in the future.

What evidence suggests that this trial's cognitive testing could be effective for episodic memory?

This trial will involve cognitive testing through three different experiments. Research has shown that cognitive testing can help improve memory. One study found that computer-based brain exercises improved memory in people with mild memory problems or dementia. Another study demonstrated that these exercises can boost both memory of past events and decision-making skills, with improvements especially noticeable in older adults with brain injuries. These findings suggest that cognitive testing could be a promising way to enhance memory and decision-making abilities. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals undergoing neurosurgical treatment of epilepsy who are interested in contributing to research on memory. It focuses on how the posterior cingulate cortex (PCC) affects decisions based on episodic memory, like recognizing if you've seen a picture before.

Inclusion Criteria

All participants are patients undergoing invasive brain monitoring for epilepsy and will be asked to consent to participation in this basic science protocol (which is focused on the patient group but is not focused on the study of epilepsy)

Exclusion Criteria

Individuals with cognitive impairment or intellectual difficulty

I am not having invasive brain monitoring for epilepsy.

I am not between the ages of 18 and 50.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experiment 1 - Episodic/Executive Switch

Participants perform a cognitive task involving the switch between episodic memory decisions and executive decisions while brain activity is recorded.

18 minutes

1 visit (in-person)

Experiment 2 - Executive Decision Task

Participants perform a cognitive task involving reward-based decisions between two options while brain activity is recorded.

15 minutes

1 visit (in-person)

Experiment 3 - Episodic Decision Task

Participants perform a cognitive task involving memory-based decisions between two options while brain activity is recorded.

15 minutes

1 visit (in-person)

Follow-up

Participants are monitored for changes in electrophysiological brain response and task performance accuracy and speed.

1 hour

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive testing

Trial Overview The study involves cognitive testing using intracranial recordings and stimulation during routine clinical monitoring. Researchers aim to understand the PCC's role in executive processes supporting memory retrieval and decision-making.

How Is the Trial Designed?

Group I: Experiment 3 - episodic decision task Experimental Treatment 1 Intervention

All enrolled participants will be asked to perform experiment 3, which is a cognitive task involving memory-based decisions between two options (pictures of people). For each decision, the two pictures will differ in memory strength and reward (e.g., familiar picture for 10 points vs. unfamiliar picture 50 points). Memory strength for each picture will be defined by how many times the picture was previously shown (e.g., 2 vs. 10 presentations) prior to performing the memory decision task. Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 15 minutes to complete.

Group II: Experiment 2 - executive decision task Experimental Treatment 1 Intervention

All enrolled participants will be asked to perform experiment 2, which is a cognitive task involving reward-based decisions between two options. For each decision, the two options will differ in their risk and reward (e.g., 100% chance of 10 points vs. 30% chance of 50 points). Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 15 minutes to complete.

Group III: Experiment 1 - episodic / executive switch Experimental Treatment 1 Intervention

All enrolled participants will be asked to perform experiment 1, which is a cognitive task involving the switch between performing episodic memory decisions (e.g., "did you eat fruit yesterday?") and executive decisions (e.g. "...does 5+3+8 = 17?"). Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 18 minutes to complete.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

The Picture Sequence Memory Test (PSMT) is a newly developed tool for assessing episodic memory in individuals aged 3 to 85, demonstrating strong test-retest reliability and construct validity based on validation data for ages 20 to 85.

The PSMT effectively correlates with established measures of episodic memory and shows a clear decline in performance with aging, making it a reliable method for evaluating memory across a wide age range.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring episodic memory across the lifespan: NIH Toolbox Picture Sequence Memory Test. Dikmen, SS., Bauer, PJ., Weintraub, S., et al.[2022]

Memory assessments in pharmaceutical trials, particularly for Alzheimer's disease, must be simple, short, and sensitive to detect changes across varying severity levels, as recommended by North American and European Medical Evaluating Agencies.

The ADAS-Cog is the standard tool for assessing memory in these trials, but there is a lack of exploration into other types of memory, such as autobiographical and prospective memory, which could provide a more comprehensive understanding of cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Memory: therapeutic approach. Clinical evaluation]. Pasquier, F.[2007]

The Real-World What-Where-When memory test effectively assesses episodic memory by requiring participants to recall specific objects, their locations, and the timing of the events, making it more reflective of real-life memory use than traditional verbal tests.

This test is not only sensitive to normal cognitive aging but also correlates well with other episodic memory tasks, providing a cost-effective and ecologically valid method for evaluating memory performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Real-world What-Where-When Memory Test. Smulders, TV., Black-Dominique, A., Choudhury, TS., et al.[2019]

Cognitive enhancers are crucial for addressing cognitive dysfunctions in various neuropsychiatric and neurodegenerative disorders, but there is a significant gap between positive animal study results and clinical trial outcomes, with a 6000% increase in rodent studies from 1982 to 2002 yielding little impact on later phases.

To improve the development of cognitive enhancers, focusing on measurable changes in attention, impulsivity, and episodic memory as disease biomarkers could enhance the congruency between preclinical and clinical studies, ultimately aiding in the discovery and validation of effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive endpoints as disease biomarkers: optimizing the congruency of preclinical models to the clinic. Day, M., Balci, F., Wan, HI., et al.[2015]

In a Phase I clinical trial with 28 healthy male volunteers, cognitive dysfunction was observed in all subjects after taking midazolam, regardless of whether they reported sedation-related adverse events (AEs).

The study found that even among individuals who did not report sedation-related AEs, a significant portion (66.7%) still exhibited notable cognitive impairment, suggesting that objective cognitive testing can reveal cognitive changes that self-reports may miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a Phase I study. Collie, A., Maruff, P., Snyder, PJ., et al.[2013]

Episodic memory, which is crucial for learning and recalling unique events, develops over time and relies on specific brain structures, making it important for neuropsychological assessments.

The review introduces the NIH Toolbox Picture Sequence Memory Test as a new standardized measure for assessing episodic memory in preschoolers, addressing challenges in evaluating this type of memory in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological assessment of memory in preschoolers. Bauer, PJ., Leventon, JS., Varga, NL.[2021]

Strict adherence to the test protocol significantly reduced missing values in the Visual Association Test (VAT) by ten times among older subjects, indicating improved test administration effectiveness.

The 15 Word Test (15WT) was found to be too demanding for 1 in 6 patients, highlighting its unsuitability for older individuals, while the VAT was favored for assessing episodic memory in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing Episodic Memory in Elderly Subjects: Not as Simple as It Looks. Boelaarts, L., Meyer, SRA., Scheltens, P., et al.[2022]

Current clinical memory tests have significant inadequacies that need to be addressed to improve their effectiveness in assessing human memory.

Recent advances in understanding memory, particularly through studies involving Korsakoff patients and older adults, highlight the need for new testing methods that better reflect the complexities of memory processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Problems in the clinical assessment of memory. Erickson, RC.[2019]

Episodic memory, which involves recalling personal experiences with context, is highly affected by aging and neurodegenerative diseases, particularly Alzheimer's, where memory deficits are often the first cognitive symptoms.

Current tests for assessing episodic memory are inadequate for clinical populations due to their complexity and reliance on verbal skills, highlighting the need for new methods that consider both behavioral and phenomenological aspects of memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on episodic-like and episodic memory. Pause, BM., Zlomuzica, A., Kinugawa, K., et al.[2021]

Cognitive impairment is a significant potential side effect of medications, yet many drug development programs fail to include thorough cognitive assessments during clinical trials.

The review emphasizes the importance of using sensitive cognitive measurements and proper study designs to accurately evaluate cognitive safety from early drug development through to post-marketing, ensuring that any cognitive risks are effectively communicated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of cognitive safety in clinical drug development. Roiser, JP., Nathan, PJ., Mander, AP., et al.[2021]

The study compared memory performance in 76 Alzheimer's disease (AD) patients, 46 with mild cognitive impairment (MCI), and 36 with anxiety/depression, revealing that AD and MCI patients performed differently from those with anxiety/depression across all memory tests.

The three-words immediate and delayed recall from the MMSE test is associated with hippocampal dysfunction, while the 10-pictures reminding test is suggested as a simple and reliable method for assessing memory in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Usefulness of the 10 pictures reminding test for memory assessment for the diagnosis of Alzheimer's disease, mild cognitive impairment and anxiety/depression]. Federico, D., Thomas-Anterion, C., Borg, C., et al.[2016]

In a study involving 12 traumatic brain injury patients, those who received memory remediation treatment showed significant improvements in memory scores compared to a control group that received no treatment.

The memory remediation treatment, which included compensatory and executive training skills, was delivered for 6 hours weekly over 2.5 weeks, demonstrating its effectiveness in enhancing memory function in patients with memory deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Executive and compensatory memory retraining in traumatic brain injury. Freeman, MR., Mittenberg, W., Dicowden, M., et al.[2019]

The Cognitive Interview technique significantly improved recall in older adults compared to standard recall methods, even after a 3-week delay.

This study highlights the effectiveness of a standardized version of the Cognitive Interview for enhancing memory recall in older adults, particularly with text-based information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cognitive Interview enhances long-term free recall of older adults. Dornburg, CC., McDaniel, MA.[2007]

The TYM test is designed to be a quick and efficient cognitive assessment tool that can be easily administered by non-specialists, addressing the need for minimal operator time.

It effectively evaluates a range of cognitive functions and is sensitive enough to detect mild Alzheimer's disease, making it a valuable tool for diagnosing dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory test tool. [2019]

Measuring cognitive function using the Cognitive Drug Research computerized assessment system in clinical trials can provide valuable insights from the very first phase of testing, helping to ensure that new medications do not impair cognitive abilities or interact negatively with other substances.

Incorporating cognitive function assessments into drug development is essential, as it allows for a nuanced understanding of how new treatments affect cognitive abilities, which is particularly important for conditions like dementia, and future advancements in testing methods, such as telephone and internet assessments, will enhance the feasibility of these evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of assessing cognitive function in drug development. Wesnes, KA.[2023]

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Cognitive safety Safety-relevant cognitive data is extremely valuable in support of regulatory submissions and drug differentiation claims. Testing for cognitive function, motor ...