Risk Disclosure for Mild Cognitive Impairment

Overseen By Corey J Bolton, PsyD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Schizophrenia, Bipolar, Epilepsy, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how to safely and effectively share blood test results that might predict Alzheimer's disease in individuals with mild cognitive impairment (MCI). Participants will receive one of two types of risk disclosure: one based on age, sex, and cognitive tests, and the other including new blood test results (Plasma p-tau risk disclosure). The researchers aim to determine if the blood test results cause more confusion or stress compared to the standard method. Adults with MCI who have a supportive partner and can speak English may be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future Alzheimer's risk assessments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this method of risk disclosure is safe for individuals with mild cognitive impairment?

Research shows that sharing Alzheimer's disease risk using plasma p-tau181 levels is generally safe. Plasma p-tau181, a protein associated with Alzheimer's disease, serves as a helpful marker for predicting memory and thinking problems. It aids in understanding disease progression but does not prevent it.

Earlier research on sharing Alzheimer's risk through other methods, such as genetic testing, has also proven safe. These studies mostly involved individuals without memory problems. Currently, the focus shifts to those with mild cognitive impairment (MCI), a condition that can lead to dementia.

The current study will examine whether sharing risk information based on plasma p-tau181 causes anxiety or distress. Previous studies found no psychological harm. This research aims to develop better ways to share risk information with patients in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to disclose risk for mild cognitive impairment (MCI). Unlike standard risk assessments that rely solely on age, sex, and cognitive screening scores, one approach in this trial includes plasma p-tau levels. Plasma p-tau is a biomarker that may provide more precise information about brain health, potentially leading to earlier and more accurate detection of cognitive decline. By incorporating this biomarker into risk assessments, researchers hope to improve how MCI is identified and managed, potentially leading to better outcomes for patients.

What evidence suggests that this trial's risk disclosure methods could be effective for mild cognitive impairment?

Research has shown that plasma p-tau181 strongly indicates changes related to Alzheimer's disease (AD). As the disease progresses, plasma p-tau181 levels rise and align with brain scans that reveal tau and amyloid proteins, which play a crucial role in AD. This biomarker could help track disease progression. In this trial, participants in the "Plasma p-tau Disclosure" arm will receive a risk estimate based on plasma p-tau results, age, sex, and cognitive screening score. This approach suggests that measuring plasma p-tau181 could effectively identify those at risk of developing dementia from mild cognitive impairment. Meanwhile, participants in the "Standard Disclosure" arm will receive a risk estimate based on age, sex, and cognitive screening score without plasma p-tau results. ^{1 2 3 5 6}

Who Is on the Research Team?

Corey J Bolton, PsyD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 60 and older with a diagnosis of amnestic mild cognitive impairment (MCI) from the Vanderbilt Alzheimer's Disease Research Center. They must have someone who interacts with them regularly to participate in study visits, speak English fluently, and be able to consent. Those with major psychiatric or neurological illnesses, significant head injuries, or acute psychological distress are excluded.

Inclusion Criteria

Consensus diagnosis of amnestic MCI by Vanderbilt Alzheimer's Disease Research Center (VADRC) clinician panel

English language fluency

I am 60 years old or older.

Exclusion Criteria

I am able to understand and make decisions about participating in this study.

History of major psychiatric illness (e.g., schizophrenia, bipolar), neurological illness (e.g., epilepsy, multiple sclerosis, Parkinson's disease), or head injury with significant loss of consciousness

Presence of acute psychological distress (i.e., Geriatric Depression Scale >10 at screening)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Educational Material Development

Development and refinement of educational materials in collaboration with health communication experts and focus groups

4-6 weeks

Risk Disclosure

Participants receive risk disclosure based on plasma p-tau181 results and other demographic factors

1 week

1 visit (in-person)

Follow-up

Participants are monitored for comprehension and psychological well-being after risk disclosure

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Plasma p-tau risk disclosure
• Standard risk disclosure

Trial Overview The study tests how best to inform people about their risk of developing dementia using a new blood test that measures plasma p-tau181 levels compared to standard methods based on age, sex, and cognitive status. Participants will receive educational materials developed by experts and their understanding and emotional well-being will be tracked immediately after disclosure and at six months.

How Is the Trial Designed?

Group I: Plasma p-tau Disclosure Experimental Treatment 1 Intervention

To receive risk estimate based on plasma p-tau results in addition to age, sex, and cognitive screening score.

Group II: Standard Disclosure Active Control 1 Intervention

To receive risk estimate based on age, sex, and cognitive screening score.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

In a study involving 250 participants over a median of 4.3 years, plasma levels of phosphorylated tau at threonine-217 (p-tau217) were found to increase significantly in individuals with preclinical and prodromal Alzheimer's disease, indicating its potential as a biomarker for monitoring disease progression.

Patients with mild cognitive impairment who later developed Alzheimer's dementia showed accelerated increases in p-tau217 compared to those who did not convert, suggesting that p-tau217 could help identify individuals at higher risk for progression to Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal plasma p-tau217 is increased in early stages of Alzheimer's disease. Mattsson-Carlgren, N., Janelidze, S., Palmqvist, S., et al.[2021]

The novel plasma p-tau181 assay is highly effective in detecting both clinical Alzheimer's disease (AD) and asymptomatic amyloid-β (Aβ) pathology, with an impressive accuracy (AUC of 0.98 for clinical AD and 0.84 for asymptomatic Aβ pathology) based on a study involving 44 AD patients and 40 spouse controls.

In contrast, the p-tau231 assay did not demonstrate the same level of efficacy, indicating that p-tau181 is a superior biomarker for identifying AD-related changes in the brain, particularly in asymptomatic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phospho-specific plasma p-tau181 assay detects clinical as well as asymptomatic Alzheimer's disease. De Meyer, S., Vanbrabant, J., Schaeverbeke, JM., et al.[2023]

In a study of 44 individuals (24 presenilin-1 E280A carriers and 20 non-carriers), higher levels of plasma p-tau217 were found in carriers, indicating a potential link to Alzheimer's disease pathology.

Baseline plasma p-tau217 levels were predictive of future amyloid and tau PET pathology as well as cognitive performance, suggesting its utility as a non-invasive biomarker for diagnosing and monitoring Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease. Aguillon, D., Langella, S., Chen, Y., et al.[2023]

The new Simoa plasma assay for phosphorylated tau (p217+tau) shows significantly elevated levels in cognitively impaired individuals with amyloid beta (Aβ) compared to cognitively unimpaired individuals, indicating its potential as a biomarker for Alzheimer's disease.

The plasma p217+tau levels correlate strongly with amyloid and tau PET imaging results, suggesting that this assay could be a reliable tool for early detection and assessment of Alzheimer's disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum. Doré, V., Doecke, JD., Saad, ZS., et al.[2022]

Plasma levels of phosphorylated tau at threonine 181 (p-tau181) can accurately distinguish between pathology-confirmed Alzheimer's disease (AD) and normal cognition (NC) individuals, achieving a high accuracy with an AUC of 0.93.

Higher levels of p-tau181 are linked to a faster decline in cognitive function and a shorter time to significant functional decline in both mild cognitive impairment (MCI) and AD dementia patients, indicating its potential as a biomarker for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma phosphorylated tau181 predicts cognitive and functional decline. Tropea, TF., Waligorska, T., Xie, SX., et al.[2023]

In a study of 1184 participants, including cognitively normal individuals and those with mild cognitive impairment or Alzheimer's dementia, plasma phosphorylated tau181 (p-tau181) levels were found to be significantly higher in those with cognitive impairment and Alzheimer's, indicating its potential as a biomarker for disease progression.

The increase in plasma p-tau181 over time was associated with various Alzheimer's disease-related changes, such as abnormal cerebrospinal fluid biomarkers, amyloid accumulation, brain atrophy, and cognitive decline, suggesting that p-tau181 could be a useful noninvasive tool for monitoring disease progression and treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease. Chen, SD., Huang, YY., Shen, XN., et al.[2021]

Blood levels of phosphorylated tau (p-tau231 and p-tau181) are significantly elevated in Alzheimer's disease (AD) patients compared to controls, indicating their potential as effective biomarkers for diagnosis, with area under the curve (AUC) values ranging from 82.2% to 90.2% across different sample types.

The study found strong correlations between serum and plasma p-tau levels, suggesting that serum could be a viable alternative for p-tau analysis in clinical settings, although absolute concentrations should be interpreted independently between serum and plasma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of serum versus plasma phospho-tau for Alzheimer's disease. Kac, PR., Gonzalez-Ortiz, F., Simrén, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9969916/

Plasma Phosphorylated Tau at Threonine 181 and ... Plasma phosphorylated tau at threonine 181 (p-tau181), a well-validated marker of Alzheimer disease (AD) pathologic change, could be a more ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05377060

Study Details | NCT05377060 | Disclosing Dementia Risk ... This study seeks to develop comprehensible educational materials to aid risk disclosure and examine the effect of risk disclosure based on plasma p-tau181 ...

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2018.02.013

Plasma phospho‐tau181 increases with Alzheimer's disease ... Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

4. psychiatryadvisor.com psychiatryadvisor.com/news/alzheimer-disease-biomarker-plasma-phosphorylated-tau-at-threonine-181-may-effectively-track-disease-progression/

Alzheimer Disease Biomarker, Plasma Phosphorylated ... Plasma phosphorylated tau at threonine 181 (p-tau181) could be an Alzheimer disease (AD)-specific biomarker which may effectively monitor ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8088291/

Plasma levels of phosphorylated tau 181 are associated ... Plasma levels of phosphorylated tau 181 are associated with cerebral metabolic dysfunction in cognitively impaired and amyloid-positive individuals.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666756823002556

Plasma p-tau181 as an outcome and predictor of ... Plasma tau phosphorylated at threonine 181 appears useful as a prognostic biomarker, in terms of predicting cognitive decline, but its utility as a prevention ...