Plasma Hydrogen Sulfide as a Biomarker for Alzheimer's Disease and Related Dementias

Study Overview
=================
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.

Official Title
-----------------
Plasma Hydrogen Sulfide as a Biomarker for Alzheimer's Disease and Related Dementias

Conditions
-----------------
Alzheimer Disease, Dementia

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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: 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.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ADRD<br>Participants in the ADRD group will have a score of greater than or equal to 17 on the ADAS-cog, a paper and pencil test of cognitive function including memory. Subgroups based on sex and race categories will also be examined. | |
| Control<br>Participants in the control group will have a score of less than 17 on the ADAS-cog, a paper and pencil test of cognitive function including memory | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Outcomes | ADAS Cog score | Prospective, single measurement | 
| Imaging Outcomes | MRI based brain volume measures, FLAIR lesion volume | Prospective, single measurement | 
| Blood Outcomes | Plasma Hydrogen sulfide including metabolites: free, acid labile, bound and total sulfides. | Prospective, single measurement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic Data | Age, Race, Sex, Socioeconomic status | Prospective, single measurement | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
biomarker, vascular disease, sex differences, race differences