Stress Response Testing for Alzheimer's Risk
(Stress-AD Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Johns Hopkins University
Must not be taking: Neuroleptics, sedative hypnotics, glucocorticoids
Disqualifiers: Smoking, psychiatric illness, neurological disorder, immune disorder, drug dependence, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that participants have not been treated with neuroleptics, sedative hypnotics, or glucocorticoids in the last six months. If you are currently taking these medications, you may need to stop them to participate.
What data supports the effectiveness of the treatment Trier Social Stress Test (TSST) for Alzheimer's risk?
The research suggests that higher stress responses, as measured by the TSST, may indicate a preclinical sign of cognitive impairment, which is related to Alzheimer's risk. This implies that the TSST could be useful in identifying individuals at risk for cognitive decline.
12345Is the Trier Social Stress Test (TSST) safe for humans?
The TSST is generally considered safe for humans, as it has been used in various studies to assess stress responses without reports of significant adverse effects. However, it can cause temporary increases in stress hormones like cortisol, which are typically well-tolerated.
12678How does the treatment in the Stress Response Testing for Alzheimer's Risk trial differ from other treatments for Alzheimer's?
This treatment is unique because it uses the Trier Social Stress Test (TSST) to assess stress response, which may help identify individuals at risk for cognitive impairment before symptoms appear. Unlike traditional Alzheimer's treatments that focus on managing symptoms, this approach aims to understand the role of stress in the disease's development.
29101112Eligibility Criteria
This trial is for English-speaking individuals aged 60 or older with mild cognitive impairment (MCI), who can consent to the study and have a 'study partner' available. They must be able to return for follow-up after two years, have a BMI between 17 and 30, and meet specific clinical criteria for MCI.Inclusion Criteria
I am a native English speaker with Mild Cognitive Impairment.
I have mild cognitive impairment and my BMI is between 17 and 30.
Subjects with Mild Cognitive Impairment (MCI) must be willing and able to return for 2-year-followup visit
+4 more
Exclusion Criteria
I have MCI and no history of major psychiatric illnesses.
I have MCI and have never had a severe head injury, stroke, or seizure.
Study Partners must be willing and able to attend study visits
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants and their study partners answer questions about daily functioning, and participants take paper-and-pencil tests and provide a blood sample.
1 day
1 visit (in-person)
Stress Procedure
Participants undergo a stress procedure involving public speaking and mental math, with stress hormone levels measured through saliva samples.
1 day
1 visit (in-person)
Follow-up
Participants and their study partners return for assessments, including blood samples and cognitive tests, to evaluate cognitive decline and neurodegeneration.
2 years
1 visit (in-person)
Participant Groups
The study uses the Trier Social Stress Test to understand if stress hormones predict cognitive decline in those at risk for Alzheimer's. It explores how genes linked to Alzheimer's affect this relationship and whether they forecast changes in cognition and biomarkers over two years.
1Treatment groups
Experimental Treatment
Group I: Trier Social Stress TestExperimental Treatment1 Intervention
All participants in the study will get undergo the same stress procedure
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins School of MedicineBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins UniversityLead Sponsor
National Institute on Aging (NIA)Collaborator
References
A Novel Cognitive Stress Test for the Detection of Preclinical Alzheimer Disease: Discriminative Properties and Relation to Amyloid Load. [2022]To examine the utility of a novel "cognitive stress test" to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders.
Cortisol reactivity to a psychosocial stressor significantly increases the risk of developing Cognitive Impairment no Dementia five years later. [2021]Alzheimer's disease (AD) patients show high cortisol levels suggesting that biological mediators of stress may play a role in the neurodegenerative process of cognitive disorders. However, there is no consensus as to whether cortisol concentrations represent a risk factor for the development of cognitive impairment. We analyzed the potential association between the incidence of cognitive impairment and cortisol concentrations under basal and acute stress conditions in 129 individuals aged 50 years or older, with preserved cognitive and functional abilities. All participants were recruited in 2011 for assessment of cognitive performance and cortisol levels. Cortisol was analyzed in saliva samples collected during two typical and consecutive days, in the morning, afternoon, and night, and also during exposure to an acute psychosocial stressor (Trier Social Stress Test - TSST). After a five-year follow-up, 69 of these volunteers were reassessed for cognitive performance, functional evaluation, memory complaints, and depression. The incidence of cognitive impairment not dementia (CIND) was 26.1 %, and was positively associated with greater TSST-induced cortisol release (responsiveness) [(95 % CI = 1.001-1.011; B = 0.006), p = 0.023]. Moreover, five years before diagnosis, participants who later developed CIND had greater responsiveness to TSST (p = 0.019) and lower cortisol awakening response (CAR: p = 0.018), as compared to those who did not develop CIND. These findings suggest that higher psychosocial stress responsiveness profiles may represent a preclinical sign of cognitive impairment.
Effects of stress on emotional memory in patients with Alzheimer's disease and in healthy elderly. [2019]ABSTRACTObjective:We aimed at examining the relation between stress markers (cortisol levels and state anxiety) with memory for emotional information in AD patients and in healthy elderly.
Stressful life events, general cognitive performance, and financial capacity in healthy older adults and Alzheimer's disease patients. [2023]The influence of stressful life events on general cognition and for the first time on financial capacity performance of patients with a diagnosis of Alzheimer's disease (AD) and in healthy controls (HC) is assessed.
Differential effects of chronic stress on anxiety-like behavior and contextual fear conditioning in the TgF344-AD rat model of Alzheimer's disease. [2022]Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to severe cognitive and functional impairments. Many AD patients also exhibit neuropsychiatric symptoms, such as anxiety and depression, prior to the clinical diagnosis of dementia. Chronic stress is associated with numerous adverse health consequences and disease states, and AD patients exhibit altered stress systems. Thus, stress may represent a causal link between neuropsychiatric symptoms and AD. To address this possibility, we examined the effects of chronic stress in the TgF344-AD rat model that co-expresses the mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9) genes. Adult male transgenic (Tg+) and wild-type (WT) rats (6-7.5 months of age), with and without a history of chronic restraint stress, were tested for footshock-induced conditioned fear and for anxiety-like behavior in the elevated plus-maze. We found that non-stressed Tg+ rats showed increased anxiety-like behavior compared to non-stressed WT rats. In contrast, Tg+ and WT rats did not differ in levels of freezing immediately following footshock or during contextual re-exposure. Additionally, stressed Tg+ rats were not significantly different from stressed WT rats on any measures of anxiety or fear. Thus, while stress has been linked as a risk factor for AD-related pathology, it appears from the present findings that two weeks of daily restraint stress did not further enhance anxiety- or fear-like behaviors in TgF344-AD rats.
Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aβ-related cognitive impairment in preclinical Alzheimer's disease after a 27-month delay interval. [2021]Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1-4, 2017). Previously, we established the scopolamine challenge test (SCT) as a "cognitive stress test" screening measure to identify individuals at risk for AD (Alzheimer's & Dementia 10(2):262-7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval.
Factor structure and scoring of the SKT test battery. [2019]The SKT (Syndrom Kurztest) has been used in the assessment of treatment responses in numerous clinical trials for treatment of dementia in German-speaking Europe. Data from 265 patients with mild to moderate Alzheimer's disease in a study conducted in the U.S. were analyzed to evaluate factor structure, common and specific subtest content, reliability, and concurrent validity. Results confirm the presence of two primary factors of memory and attention. Test-retest reliability of the factor scores was estimated to be .75 and .93. Test-retest reliability of the composite SKT total score was .90. The correlations between the SKT memory and attention factor scores and the MMSE and ADAS measurements of dementia also support validity with regard to the broader construct of cognitive dysfunction.
Stress and verbal memory in patients with Alzheimer's disease: different role of cortisol and anxiety. [2020]Objectives: Chronic stress has shown to have marked effects on learning and memory. A broader understanding of these effects has special interest in the context of Alzheimer's disease (AD). This study aims to analyze the moderating effect of cognitive impairment in the relationships between stress and verbal memory performance by considering biological and psychological measures of stress. Method: The sample consisted of 80 AD patients and 104 healthy controls. Salivary cortisol and state anxiety was measured as stress markers. Memory Alteration test (M@T) and Hopkins verbal learning test (HVLT-R) were used to measure verbal memory. Results: In controls, cortisol level was negatively associated with HVLT-R total, learning and delayed recall scores as well as M@T free recall scores, while in patients, such associations were not significant. In this group, cortisol negative effects were limited to HVLT-R learning and M@T semantic memory scores. In both groups, anxiety was associated with better M@T encoding and free recall scores. Besides, inverted U-shaped relationships were observed between anxiety and HVLT-R total recall and learning scores as well as M@T orientation scores. Conclusion: Cortisol levels and anxiety are differentially associated with memory performance in older adults. In general, the negative relationship between cortisol levels and memory observed in healthy elderly weakens in AD. However, moderate state anxiety levels seem to be associated with a better memory performance in AD patients and in healthy elderly.
The Trier Social Stress Test: Principles and practice. [2022]Researchers interested in the neurobiology of the acute stress response in humans require a valid and reliable acute stressor that can be used under experimental conditions. The Trier Social Stress Test (TSST) provides such a testing platform. It induces stress by requiring participants to make an interview-style presentation, followed by a surprise mental arithmetic test, in front of an interview panel who do not provide feedback or encouragement. In this review, we outline the methodology of the TSST, and discuss key findings under conditions of health and stress-related disorder. The TSST has unveiled differences in males and females, as well as different age groups, in their neurobiological response to acute stress. The TSST has also deepened our understanding of how genotype may moderate the cognitive neurobiology of acute stress, and exciting new inroads have been made in understanding epigenetic contributions to the biological regulation of the acute stress response using the TSST. A number of innovative adaptations have been developed which allow for the TSST to be used in group settings, with children, in combination with brain imaging, and with virtual committees. Future applications may incorporate the emerging links between the gut microbiome and the stress response. Future research should also maximise use of behavioural data generated by the TSST. Alternative acute stress paradigms may have utility over the TSST in certain situations, such as those that require repeat testing. Nonetheless, we expect that the TSST remains the gold standard for examining the cognitive neurobiology of acute stress in humans.
Validation of an online version of the Trier Social Stress Test in a study of adolescents. [2023]The Trier Social Stress Test (TSST) is the most widely used protocol for activating a stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis and other stress-mediating systems. A number of variants of the TSST exist, including ones for children, groups, and virtual reality. All of these versions, though, require in-person assessment. The COVID-19 pandemic has made in-person assessment impossible or extremely difficult and potentially dangerous. The purpose of this study was to validate a completely remote, online, version of the TSST for children.
Mood and autonomic responses to repeated exposure to the Trier Social Stress Test for Groups (TSST-G). [2014]A group version of the Trier Social Stress Test (TSST-G) was introduced as a standardized, economic and efficient tool to induce a psychobiological stress response simultaneously in a group of subjects. The aim of the present study was to examine the efficacy of the TSST-G to repeatedly induce an affective and autonomic stress response while comparing two alternative protocols for the second examination.
Acute psychosocial stress: does the emotional stress response correspond with physiological responses? [2022]Most stress experiences are accompanied by physiological and psychological responses. Laboratory stressors such as the Trier Social Stress Test (TSST) induce reliable stress responses, which are mainly assessed for biological parameters such as cortisol. The associations between physiological and psychological responses to the TSST have been rarely investigated and are addressed in this review. Up to August 2011, 358 studies were published in PubMed examining the impact of the TSST (71%) or variations of the protocol. A total of 49 studies were considered based on the following three inclusion criteria: (1) exposure to the standard TSST or slightly modified TSST versions, (2) at least one assessment of subjective emotional stress experience before, during or after the TSST, (3) reported associations between acute physiological and emotional stress measures. Significant correlations between cortisol responses and perceived emotional stress variables were found in approximately 25% of the studies. Our descriptive analysis revealed various essential elements that potentially contribute to this apparent dissociation, reaching from differing assessment approaches and methodological features of the stress protocols to possible mediating factors and interindividual differences in the degree of psychophysiological correspondence.