Plasma Hydrogen Sulfide as a Biomarker for Alzheimer's Disease and Related Dementias
- Conditions
- DementiaAlzheimer Disease
- Registration Number
- NCT05060848
- Lead Sponsor
- Louisiana State University Health Sciences Center Shreveport
- Brief Summary
Hydrogen sulfide is a signaling molecule that is important for vascular health. Because vascular factors such as hypertension and high cholesterol are risk factors for Alzheimer's disease and related dementias, we hypothesize that hydrogen sulfide plays an important role in brain health as well. We will compare blood levels of hydrogen sulfide across groups of people with and without dementia. We will also look at the relationship between hydrogen sulfide, cognitive dysfunction and measures of brain microvascular disease examine the contribution of hydrogen sulfide to cognitive decline. Our goal is to identify a biomarker of vascular dysfunction in dementia.
- Detailed Description
We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. There is accumulating evidence that vascular factors such as hypertension, hypercholesterolemia, and type 2 diabetes are associated with increased risk of Alzheimer's disease and related dementias (ADRD). Furthermore, in the brain, H2S acts as a neurotransmitter/second messenger produced following nerve excitation. It also modulates N-methyl-D-aspartate (NMDA) receptors during long term potentiation for memory consolidation. Three biochemical forms of reactive sulfur pools exist: free H2S, acid-labile (e.g. iron-sulfur clusters) and bound sulfide (e.g. persulfides, polysulfides). We hypothesize that H2S becomes dysregulated in ADRD, where vascular and cognitive functions are linked. We will use analytical biochemical methods to measure plasma H2S and its metabolites, and 3T MRI to evaluate indicators of microvascular disease in ADRD. We will compare H2S levels in people with and without cognitive dysfunction consistent with ADRD, and determine the specificity and sensitivity of H2S indistinguishing people with and without cognitive dysfunction. In addition, because previous studies report differences in the incidence and prevalence of ADRD by race and sex, we will compare outcomes across these groups as well. Finally, we will examine the potentially mediating role of H2S in the relationship between cognitive function and microvascular disease.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 100
- All participants must be aged >55 years with English as the 1⁰ language, with stable permitted medications for <4 weeks, geriatric depression scale score <6, visual and auditory acuity adequate to perform tests, and history of education excluding developmental cognitive abnormalities.
- Exclusion criteria are history of significant neurologic disease or mental illness, unstable medical conditions that could interfere with completion of study, substance abuse within 2 years, contraindications to MRI, abnormal findings on MRI, history of chronic kidney disease, and investigational agents within 1 month of participation.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Blood Outcomes Prospective, single measurement Plasma Hydrogen sulfide including metabolites: free, acid labile, bound and total sulfides.
Cognitive Outcomes Prospective, single measurement ADAS Cog score
Imaging Outcomes Prospective, single measurement MRI based brain volume measures, FLAIR lesion volume
- Secondary Outcome Measures
Name Time Method Demographic Data Prospective, single measurement Age, Race, Sex, Socioeconomic status
Trial Locations
- Locations (1)
LSU Health Shreveport Center for Brain Health
🇺🇸Shreveport, Louisiana, United States