Mild Cognitive ImpairmentStress-ADNCT05795634
Cognitive Vulnerability to Stress in Individuals at Risk for Alzheimer's Disease
A study testing Trier Social Stress Test in people with Mild Cognitive Impairment and Alzheimer Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn about how genetics and the response to stress predicts cognitive decline in individuals with mild cognitive impairment. The main question[s] it aims to answer are: Does the hormone response to acute stress predict the degree of cognitive impairment following acute stress? Do… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease
- What is being tested?
- Trier Social Stress Test
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2023to 1 Mar 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 21 or older
- Able to participate in an interview
- Willing and able to attend study visits
- Willing and able to return for 2-year-followup visit
Who cannot join
- Current smoker
- Current or past history of major psychiatric illness, including schizophrenia, bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder
- Neurological disorder, including Parkinson's disease, Huntington's disease
- Current or past history of immune disorder, including multiple sclerosis
- Current or past history of drug dependence
- Treatment within the last six months with: neuroleptics, sedative hypnotics, or glucocorticoids
Show all 16Show fewer
- History of head injury with loss of consciousness for more than ½ hour, stroke, or seizure
- General surgery within the last 3 months
- Sensory impairment (poor vision or hearing) significant enough to interfere with ability to provide valid cognitive test data
- Clinical and Cognitive Criteria for MCI due to AD
- Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e., historical or observed evidence of decline over time)
- Objective evidence of impairment in one or more cognitive domains, typically including memory (i.e., formal or bedside testing to establish level of cognitive function in multiple domains)
- Preservation of independence in functional abilities
- Not demented
- Etiology of MCI consistent with AD pathophysiological process
- Unwilling to answer questions about the participant with MCI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins School of Medicine
Baltimore, Maryland, 21224
Nick Bienko, MA, 410-550-2036, nbienko1@jhmi.edu
About this study
Official title: Cognitive Vulnerability to Stress in Individuals at Risk for Alzheimer's Disease (Stress-AD)
The goal of this clinical trial is to learn about how genetics and the response to stress predicts cognitive decline in individuals with mild cognitive impairment.
The main question[s] it aims to answer are:
Read more
- Does the hormone response to acute stress predict the degree of cognitive impairment following acute stress?
- Do genes associated with the risk for Alzheimer's disease influence the relationship between stress hormone response to stress and cognitive impairment following stress?
- Do cognitive impairment following acute stress and genes associated with the risk for Alzheimer's disease predict cognitive decline and change in biomarkers for Alzheimer's disease 2 years later?
Participants will have 3 in-person study visits. The first 2 will occur at baseline and the 3rd visit will occur 2 years later. During the visits, participants will provide blood and saliva samples, undergo a 10-minute social stress procedure, complete questionnaires, and take tests of memory and other thinking skills. Someone who knows the participant (a "study partner") will be asked questions about the participant's daily functioning at the first and 3rd study visits.
Read the detailed description
In the wake of discouraging results from treatment trials in Alzheimer's disease (AD), there is emerging consensus that the lack of efficacy in these trials is attributable to heterogeneity in the course of AD. Among the potential causes of heterogeneity, the investigators aim to focus on vulnerability to acute stress. Although associations between stress and the risk of AD are well established, these findings have not been used to inform AD intervention efforts. The investigators aim to address this crucial gap. Considering that in healthy individuals, acute stress can impair cognition in those who have risk factors for AD, the investigators propose that these individuals may represent a specific endophenotype who could be targeted for AD treatment trials. The investigators' prior findings implicate the endocrine stress response as an important component of AD risk that warrants further study.
The investigators aim to conduct a prospective study to examine the associations among the acute endocrine stress response, cognitive impairment following acute stress, and subsequent cognitive decline. For the investigators' basic study design, the investigators will induce acute stress with the Trier Social Stress Test (TSST; 5 minutes of public speaking and 5 minutes of mental arithmetic) and then administer a battery of cognitive tests. Two cognitive domains-memory and executive functioning-will be the primary cognitive outcomes. Salivary samples collected at fixed intervals will be used to measure stress hormone response; cortisol will the primary endocrine hormone outcome. The investigators will also examine the influence of apolipoprotein E (APOE) gene polymorphisms and polygenic risk scores, conduct sex-stratified analyses, and collect blood-based biomarkers for AD.
The investigators' study has 3 primary aims:
- To determine the association between endocrine response to acute stress and memory and executive test performance following acute stress in individuals with MCI due to AD.
- To examine the moderating effect of APOE genotype and polygenic risk score derived from genome wide genotyping on the association between endocrine response to acute stress and cognitive test performance following acute stress in individuals with MCI due to AD.
- To determine predictors of cognitive decline and neurodegeneration at 2-year follow-up.
Secondary Aims: Conduct the analyses from Specific Aims 1-3 in men and women separately in order to identify sex-specific predictors of stress-induced memory and executive impairment and cognitive decline after 2 years. As an exploratory aim, the investigators will examine the influence of personality factors and stressful life events on the hypothesized associations.
For this study, participants will come to the clinic for 3 study visits. For the first visit, participants will be asked to bring someone who knows the participant well (a "study partner"). During that visit, participants and the participants' study partners will answer questions about the participant's daily functioning. In addition, participants (but not the participants study partners) will take paper-and-pencil tests and provide a blood sample. About one month later, participants will return for a second study visit, but the participants' study partner does not need to come to that visit. During that second visit, participants will undergo a brief procedure (public speaking and mental math) that is designed to cause stress, during which the investigators will measure participants' stress hormones by asking participants to provide the investigators with samples of the participants' saliva. Two years later, participants and the participants' study partners will return for Visit 3. At that visit, the investigators will ask participants to provide another blood sample and complete tests of memory and other thinking skills. Study partners will answer questions about the participants during this visit but will not take any tests or provide a blood sample.
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Being tested
- Trier Social Stress Test
- Keywords
- Stress, Neuropsychology, Endocrine, Genetics, Blood biomarkers
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trier Social Stress TestBehavioural
Acute psychosocial stress procedure; 5 minutes of public speaking and 5 minutes of mental arithmetic
| Study group | Role | What they receive |
|---|---|---|
| Trier Social Stress Test | Other | All participants in the study will get undergo the same stress procedure Receives: Behavioral: Trier Social Stress Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean memory test composite score
Change in the mean composite score of the following memory tests: Neuropsychological Assessment Battery Word List Memory test, Morris Revision test, and a computerized Pattern Separation Task, with higher composite score indicating better memory
Measured: Baseline and Visit 2 (up to 1 month) and Baseline to Visit 3 (up to 2 years)
Change in mean executive test composite score
Change in the mean composite score of the following executive tests: phonemic (letter) fluency test, part B of the Trial Making Test, and the backwards trial of a Digit Span task, with higher composite score indicating better executive functioning
Measured: Baseline and Visit 2 (up to 1 month) and Baseline to Visit 3 (up to 2 years)
Secondary outcomes (1)
Change (in nanogram per liter; ng/L) in level of neurofilament light (NF-L)
Change in a blood biomarker of neurodegeneration, with higher levels indicating greater neurodegeneration
Measured: Baseline to Visit 3 (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2023
- Study start1 Mar 2023
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective study using baseline characteristics to predict outcomes
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Cynthia A Munro, PhD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05795634
- Sponsor's protocol ID
- IRB00313479
- Other IDs
- R01AG065171
- Acronym
- Stress-AD
- Status last verified
- Jan 2026
- First submitted
- 7 Mar 2023
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study investigators are committed to resource sharing, according to NIH policy. At the conclusion of the study, after the final freeze to the database, a public use database will be created and made available along with specifications for its use. Johns Hopkins University will share anonymized genomic sequence data by depositing these data in the database of Genotypes and Phenotypes (dbGaP) (a controlled-access database funded by NIH). In addition, the investigators will share data from biosamples (saliva and blood samples), including genotype data, at the time of publication of the primary results or within 9 months of database lock, whichever comes first. These data will be shared via the Alzheimer's Clinical Trials Consortium (ACTC), and/or the National Alzheimer's Coordinating Center (NACC).
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Vulnerability to Stress in Individuals at Risk for Alzheimer's Disease (Stress-AD)
- ClinicalTrials.gov ID
- NCT05795634
- Acronym / sponsor ID
- Stress-AD / IRB00313479
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Keywords
- Stress, Neuropsychology, Endocrine, Genetics, Blood biomarkers
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 3 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn about how genetics and the response to stress predicts cognitive decline in individuals with mild cognitive impairment.
The main question[s] it aims to answer are:
- Does the hormone response to acute stress predict the degree of cognitive impairment following acute stress?
- Do genes associated with the risk for Alzheimer's disease influence the relationship between stress hormone response to stress and cognitive impairment following stress?
- Do cognitive impairment following acute stress and genes associated with the risk for Alzheimer's disease predict cognitive decline and change in biomarkers for Alzheimer's disease 2 years later?
Participants will have 3 in-person study visits. The first 2 will occur at baseline and the 3rd visit will occur 2 years later. During the visits, participants will provide blood and saliva samples, undergo a 10-minute social stress procedure, complete questionnaires, and take tests of memory and other thinking skills. Someone who knows the participant (a "study partner") will be asked questions about the participant's daily functioning at the first and 3rd study visits.
Detailed description
In the wake of discouraging results from treatment trials in Alzheimer's disease (AD), there is emerging consensus that the lack of efficacy in these trials is attributable to heterogeneity in the course of AD. Among the potential causes of heterogeneity, the investigators aim to focus on vulnerability to acute stress. Although associations between stress and the risk of AD are well established, these findings have not been used to inform AD intervention efforts. The investigators aim to address this crucial gap. Considering that in healthy individuals, acute stress can impair cognition in those who have risk factors for AD, the investigators propose that these individuals may represent a specific endophenotype who could be targeted for AD treatment trials. The investigators' prior findings implicate the endocrine stress response as an important component of AD risk that warrants further study.
The investigators aim to conduct a prospective study to examine the associations among the acute endocrine stress response, cognitive impairment following acute stress, and subsequent cognitive decline. For the investigators' basic study design, the investigators will induce acute stress with the Trier Social Stress Test (TSST; 5 minutes of public speaking and 5 minutes of mental arithmetic) and then administer a battery of cognitive tests. Two cognitive domains-memory and executive functioning-will be the primary cognitive outcomes. Salivary samples collected at fixed intervals will be used to measure stress hormone response; cortisol will the primary endocrine hormone outcome. The investigators will also examine the influence of apolipoprotein E (APOE) gene polymorphisms and polygenic risk scores, conduct sex-stratified analyses, and collect blood-based biomarkers for AD.
The investigators' study has 3 primary aims:
- To determine the association between endocrine response to acute stress and memory and executive test performance following acute stress in individuals with MCI due to AD.
- To examine the moderating effect of APOE genotype and polygenic risk score derived from genome wide genotyping on the association between endocrine response to acute stress and cognitive test performance following acute stress in individuals with MCI due to AD.
- To determine predictors of cognitive decline and neurodegeneration at 2-year follow-up.
Secondary Aims: Conduct the analyses from Specific Aims 1-3 in men and women separately in order to identify sex-specific predictors of stress-induced memory and executive impairment and cognitive decline after 2 years. As an exploratory aim, the investigators will examine the influence of personality factors and stressful life events on the hypothesized associations.
For this study, participants will come to the clinic for 3 study visits. For the first visit, participants will be asked to bring someone who knows the participant well (a "study partner"). During that visit, participants and the participants' study partners will answer questions about the participant's daily functioning. In addition, participants (but not the participants study partners) will take paper-and-pencil tests and provide a blood sample. About one month later, participants will return for a second study visit, but the participants' study partner does not need to come to that visit. During that second visit, participants will undergo a brief procedure (public speaking and mental math) that is designed to cause stress, during which the investigators will measure participants' stress hormones by asking participants to provide the investigators with samples of the participants' saliva. Two years later, participants and the participants' study partners will return for Visit 3. At that visit, the investigators will ask participants to provide another blood sample and complete tests of memory and other thinking skills. Study partners will answer questions about the participants during this visit but will not take any tests or provide a blood sample.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective study using baseline characteristics to predict outcomes
| Arm | Type | Receives |
|---|---|---|
| Trier Social Stress Test | Other | Behavioral: Trier Social Stress TestAll participants in the study will get undergo the same stress procedure |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 21 or older
- Able to participate in an interview
- Willing and able to attend study visits
- Willing and able to return for 2-year-followup visit
Key exclusion criteria (16 listed)
- Current smoker
- Current or past history of major psychiatric illness, including schizophrenia, bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder
- Neurological disorder, including Parkinson's disease, Huntington's disease
- Current or past history of immune disorder, including multiple sclerosis
- Current or past history of drug dependence
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trier Social Stress TestAcute psychosocial stress procedure; 5 minutes of public speaking and 5 minutes of mental arithmetic | Behavioural | Trier Social Stress Test |
Primary outcome
Change in mean memory test composite score
Time frame: Baseline and Visit 2 (up to 1 month) and Baseline to Visit 3 (up to 2 years)
Change in the mean composite score of the following memory tests: Neuropsychological Assessment Battery Word List Memory test, Morris Revision test, and a computerized Pattern Separation Task, with higher composite score indicating better memory
Change in mean executive test composite score
Time frame: Baseline and Visit 2 (up to 1 month) and Baseline to Visit 3 (up to 2 years)
Change in the mean composite score of the following executive tests: phonemic (letter) fluency test, part B of the Trial Making Test, and the backwards trial of a Digit Span task, with higher composite score indicating better executive functioning
1 secondary outcome
Change (in nanogram per liter; ng/L) in level of neurofilament light (NF-L)
Time frame: Baseline to Visit 3 (up to 2 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Individual participant dataSharing planned: Yes. Study investigators are committed to resource sharing, according to NIH policy. At the conclusion of the study, after the final freeze to the database, a public use database will be created and made available along with specifications for its use. Johns Hopkins University will share anonymized genomic sequence data by depositing these data in the database of Genotypes and Phenotypes (dbGaP) (a controlled-access database funded by NIH). In addition, the investigators will share data from biosamples (saliva and blood samples), including genotype data, at the time of publication of the primary results or within 9 months of database lock, whichever comes first. These data will be shared via the Alzheimer's Clinical Trials Consortium (ACTC), and/or the National Alzheimer's Coordinating Center (NACC).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cynthia A Munro, PhD principal investigator
Johns Hopkins School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Trier Social Stress Test in people with Mild Cognitive Impairment and Alzheimer Disease, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cynthia A Munro, PhD (410-550-6271, cmunro@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mean memory test composite score (time frame: Baseline and Visit 2 (up to 1 month) and Baseline to Visit 3 (up to 2 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.