Ignite Creation Date:
2024-07-17 @ 10:49 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06466655
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-06-04
Brief Title:
Daily Stress and Vascular Function in Midlife as a Risk Factor for Cognitive Decline
Sponsor:
University of Delaware
Organization:
University of Delaware
Study Overview
Official Title:
Accelerated Vascular Aging in Midlife as a Mechanism Linking Daily Stress to Cognitive Decline
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to better understand how day-to-day stress affects cardiovascular health and brain function in middle-aged adults The main question is aims to answer is whether the link between daily stress and vascular dysfunction is a potential mechanism of increased risk for future cognitive decline Participants will complete two 15-day testing cycles separated by 6 months During each cycle participants will complete two daily assessments of stress and brain health using an online survey tool for 14-consecutive days On the last day of each cycle vascular function will be assessed during a laboratory visit
Detailed Description:
Nearly one-third of adults 65 years and older have mild cognitive impairment or dementia correspondingly Alzheimers disease and related dementias ADRD are now one of the leading causes of morbidity and mortality in the US Because of global demographic trends toward increasingly older populations this is a looming public health crisis with associated costs projected to soon exceed 1 trillion Thus there is an urgent need to identify the mechanistic underpinnings of modifiable risk factors for ADRD in midlife in order to establish novel biological targets for therapeutic intervention strategies that can be implemented earlier in the aging trajectory and prior to clinically detectable overt cognitive deficits which are difficult to remediate by current treatments Accordingly the long-term goal is to determine whether and to what extent mitochondrial reactive oxygen species mtROS-induced impairments in peripheral endothelium-dependent dilation EDD explain how daily stress impacts real-world cognitive function in middle-aged adults As a necessary first step towards developing a competitive NIH R01 empirically investigating this possibility the objective of this pilot proposal is to 1 establish the feasibility and efficacy of our methodological approach and 2 generate hypothesis-specific micro-longitudinal preliminary data Aim 1 will examine the stability and temporal patterning of intra-individual dynamic fluctuations in daily stress processes and daily cognitive function in middle-aged adults within and between bursts Aim 2 will determine the indicators of daily stress and daily cognitive function most strongly related to peripheral endothelial function in middle-aged adults The hypotheses are that 1 greater negative affective responsivity to daily stressors 2 more attentional lapses and 3 slower processing speed will be related to reductions in peripheral EDD secondary to increased mtROS production
A small community sample of cognitively unimpaired middle-aged males and females n20 40-55 yrs will be recruited Participants will be recruited from New Castle County Delaware DE and surrounding regions and will be representative of the sexethnicracial population of DE After providing verbal and written consent all participants will undergo a clinical exam for signs and symptoms of chronic disease by clinical nursing staff This will include a complete health history females will also complete a gynecological history including a 3-mo menstrual cycle recall physical exam anthropometry resting hemodynamics and a 12-lead electrocardiogram and basic blood biochemistry complete blood count lipid profile renal function electrolytes HbA1c fasting glucose and insulin
The investigators will assess multiple dynamic aspects of daily stress processes and real-world daily cognitive function for 14 consecutive days mobile app Using the framework established by the investigative team this high-resolution phenotyping approach allows for the precise intra-individual quantification of exposure and responsivity to daily stressors as they occur in during routine daily life Concurrently the investigators will obtain frequent daily snapshots ie 4 assessments per day of multiple clinically relevant dimensions of both subjective self-report and objective performance-based cognitive function This approach is situated within the Mobile Monitoring of Cognitive Change M2C2 infrastructure and is a reliable accurate sensitive and ecologically valid approach to detect everyday difficulties in cognitive function in complex real-world environments Immediately after completion of the ambulatory assessments ie Day 15 the investigataors will use orthogonal laboratory-based techniques to pharmaco-dissect the regulation of microvascular endothelial function in vivo and to quantify mitochondrial redox balance ex vivo Each participant will complete two 15-day measurement bursts separated by 6 months All laboratory visits will be performed at the same time of day 7a-12p and 12-hr postprandial Every attempt will be made to schedule the experimental visits for premenopausal females during the early follicular phase of their menstrual cycle or the low hormoneplacebo phase of hormonal contraception however given anticipated challenges in this regard serum concentrations of sex hormones will also be measured at each visit
Ambulatory Assessment Protocol Days 1-14 Participants will complete 4 daily assessments at each they will complete brain games and subjectively report on their cognitive function as well as on several contextual variables eg affect stress shortened for momentary administration Each assessment will take 4 min The first assessment of the day will also include a brief survey 2 min asking about sleep health quality and quantity modified Pittsburgh Sleep Quality Inventory morning outlook emotions physical symptoms and anticipatory stress Daily stress processes will be assessed each day during the last daily assessment using an adapted version of the Daily Inventory of Stressful Events DISE 8 min Daily cognitive function will be assessed in multiple domains subjective and objective
Laboratory Assessment of Peripheral Endothelial Function Day 15 Microvascular endothelial function will be assessed using intradermal microdialysis coupled with laser Doppler flowmetry Two intradermal microdialysis probes CMA Linear 31 probe 55 kDa will be inserted into the dermal layer of the ventral forearm and perfused with either lactated Ringers solution control or MitoTempol 05 mM to scavenge mitochondrial-derived superoxide Red cell flux will be continuously measured via integrated laser Doppler flowmeters Mean arterial pressure will be measured via brachial auscultation every 4 min A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically as previously described
A small community sample of cognitively unimpaired middle-aged males and females n20 40-55 yrs will be recruited Participants will be recruited from New Castle County Delaware DE and surrounding regions and will be representative of the sexethnicracial population of DE After providing verbal and written consent all participants will undergo a clinical exam for signs and symptoms of chronic disease by clinical nursing staff This will include a complete health history females will also complete a gynecological history including a 3-mo menstrual cycle recall physical exam anthropometry resting hemodynamics and a 12-lead electrocardiogram and basic blood biochemistry complete blood count lipid profile renal function electrolytes HbA1c fasting glucose and insulin
The investigators will assess multiple dynamic aspects of daily stress processes and real-world daily cognitive function for 14 consecutive days mobile app Using the framework established by the investigative team this high-resolution phenotyping approach allows for the precise intra-individual quantification of exposure and responsivity to daily stressors as they occur in during routine daily life Concurrently the investigators will obtain frequent daily snapshots ie 4 assessments per day of multiple clinically relevant dimensions of both subjective self-report and objective performance-based cognitive function This approach is situated within the Mobile Monitoring of Cognitive Change M2C2 infrastructure and is a reliable accurate sensitive and ecologically valid approach to detect everyday difficulties in cognitive function in complex real-world environments Immediately after completion of the ambulatory assessments ie Day 15 the investigataors will use orthogonal laboratory-based techniques to pharmaco-dissect the regulation of microvascular endothelial function in vivo and to quantify mitochondrial redox balance ex vivo Each participant will complete two 15-day measurement bursts separated by 6 months All laboratory visits will be performed at the same time of day 7a-12p and 12-hr postprandial Every attempt will be made to schedule the experimental visits for premenopausal females during the early follicular phase of their menstrual cycle or the low hormoneplacebo phase of hormonal contraception however given anticipated challenges in this regard serum concentrations of sex hormones will also be measured at each visit
Ambulatory Assessment Protocol Days 1-14 Participants will complete 4 daily assessments at each they will complete brain games and subjectively report on their cognitive function as well as on several contextual variables eg affect stress shortened for momentary administration Each assessment will take 4 min The first assessment of the day will also include a brief survey 2 min asking about sleep health quality and quantity modified Pittsburgh Sleep Quality Inventory morning outlook emotions physical symptoms and anticipatory stress Daily stress processes will be assessed each day during the last daily assessment using an adapted version of the Daily Inventory of Stressful Events DISE 8 min Daily cognitive function will be assessed in multiple domains subjective and objective
Laboratory Assessment of Peripheral Endothelial Function Day 15 Microvascular endothelial function will be assessed using intradermal microdialysis coupled with laser Doppler flowmetry Two intradermal microdialysis probes CMA Linear 31 probe 55 kDa will be inserted into the dermal layer of the ventral forearm and perfused with either lactated Ringers solution control or MitoTempol 05 mM to scavenge mitochondrial-derived superoxide Red cell flux will be continuously measured via integrated laser Doppler flowmeters Mean arterial pressure will be measured via brachial auscultation every 4 min A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically as previously described
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None